3.4.12.9 the Temporal Bone of Patient Ip

Home , Dacryon, Internal auditory meatus, Pterygomaxillary fissure

3.4.12.9 The Temporal Bone of patient Ip

Distances (Figure 3.30(n)):

Squamous Temporal Bone: The squamous temporal bone was not measurable in this child due

to lack of visibility of the asterion (as), sphenion (spt) and the stylomastoid foramen (smÐ. Extemal Auditory Meatus: The configuration of the external auditory meatus was abnormal and asymmetrical, with increased distances recorded on both sides (eampl-pol, pol-eamal, eamir- eampr, eamar-eamir).

Zygomatic Process: The length of the zygomatic arch (ztl-aul, ztr-aur) was decreased bilaterally. The articular fossa height (afl-ael, afr-aer) was normal, however, posteriorly the left EAM-

articular fossa length (eamal-afl) was increased.

Petrous Temporal Bone (Figure 3.30(o)): The prominence of the mastoid process (mal-jfl1, mar-jflr) was increased bilaterally compared with the experimental standard. The distances of the temporal bone showed the right jugular foramen to be narrowed (flr-jfmr) with an similar tendency on the left. The inferior petrous temporo-occipital suture (fml-ptsl, jfrnr-ptsr) was increased in length.

Dimensions (Figure 3.30(o)): The petrous temporal ridge distance (petal-petpl, petar-petpr) was increased bilaterally. The dimensions between the temporal bones was increased between the external auditory meatus (pol-por). The angles of the auditory canal (pol-iamViamr-por), the

petrous temporal bone angles (petpl-petaVpetar-petpr) and the zygoma projection (petal-aul-ztl, petar-aur-ztr) were not significantly different from the experimental standard.

Discussion: Bony distortion was found at the external auditory meatus and the zygomatic arch which was reduced in length. The jugular foramen was nanowed while the temporal occipital suture medially and the distance to the mastoid laterally were increased. The overall length of the petrous ridge was also increased. This was reflected in the significantly increased distances between the external auditory canals. The distances between the internal auditory meatus and jugular foramen were relatively normal. There appeared to be lengthening of the petrous temporal bone at the expense of narrowing of the jugular foramen and this would be consistent with sutural involvement and compensatory bone lengthening.

Page 276 Crouzon Syndrome Figure 3.30(n) Z Scores of the Distances of the Temporal Bone for Patient IP compared with the 2 Year Old Experimental Standard

Z score Squamous External Auditory Meatus Zygomatic Process t4 L R L R L R t2

a 4

-6 LL Ê!! eØdç '=Àôd= Èo d ã çÐ!Èi çoÈÊ- *f E E Ê. b É ÀÉ tr = a:'=d f 133f f f 3_3. f À t s ås ü q,õäö9 dçlJe k oØà-ñ o d Ed 9Ë* Ñ N c Ri= tr= d ã E 9Ë É trtroÀtr ã:E È o ñd trtroÈtr o oo oodõ

Figure 3.30(o) Z Scores of the Measurements of the Temporal Bone for Patient IP compared with the 2 Year Old Experimental Standard

Z score Petrous Dimensions Angles 8.00 L R L R

6.00

4.00

200

0.00

-2.00

-4.00

dd.=ó d a .- d o.ã .aEzz e +ñ ñ 4ti+P BoäEä+'Edètli¿ !dr lñol LdùJ tr.'dd -B-x+ Ë çod É ã 3 Ë E 3.Ê 3" 3- '- .f?Ee3-8. KP õ.

Chapter 3 Page 277 3.4.12.LO The Parietal Bone of patient Ip

Distances: The key landmarks for the parietal bone for Patient IP were not visible due to suture

fusion and could not be reliably estimated. Therefore the parietal bone was not measured and a

pat[ern profile of Z scores was not generated for the parietal bone. The measurement data for

the experimental standard are reported in Appendix 2.

3.4.12.11 The Occipital Bone of Patient IP

Distances (Figure 3.30(p)): The medial temporo-occipital suture (inferior) (fml-ptsl, jfmr-prsr)

was bilaterally significantly increased in length compared with the experimental standard. The

left anterior foramen magnum distance (ba-fmll) and the right posterior foramen magnum distance (fmlr-o) were increased. The inferior spheno-occipital synchondrosis was normal (see sphenoid and cranial case sutures).

Dimensions (Figure 3.30(p)): The dimensions were not significantly different from the experimental standard.

Discussion: The occipital bone was involved medially along the sutures with the temporal bone and also laterally where the calvarial sutures were fused (see temporal bone).

Figure 3.30(p) Z Scores of the Measurements of the Occipital Bone for patient rP compared with tlne 2 Year old Experimental standard

Z score Distances 6.00 Dimensions L R 5.00

4.00

3.00

2.00 l.00

0.00

-1.00 _a -2.00 e?qË.È E i3 o -! o{ o. 'Y '1ì ;a q-i o- È =o¡o ,l Oo, oo Ø-l- !ËÊ'1". I E*EÉlEr! -o E - I Èo. tst€.- ¡- È ëË a -8.È-3È oo q: ÈÈ

Page 278 Crouzon Syndrome 3.4.L2.12 The Cranial Base Sutures of Patient IP

Anterior Cranial Fossa (Figure 3.30(q)): The majority of distances measured were abnormal.

The spheno-ethmoid synchondrosis (es-cppl, es-cppr) was increased in length. The spheno- frontal suture in the anterior cranial fossa (cppl-spal, cppr-spar) was of normal length, while in the orbit, the suture (spal-zfsl, spar-zfsr) was reduced in length. The spheno-zygomatic suture

(zfsl-gwll, zfsr-gwlr) length was increased.

Middle Cranial Fossa (Figure 3.30(q)): The lateral spheno-squamous temporal suture (gwll- fisl) was increased in length on the left side.

Posterior Cranial Fossa (Figure 3.30(q)): The medial temporo-occipital suture (inferior) Cfml- ptsl, jfmr-ptsr) and the occipital mastoid suture (superior) fiflI-petpl, jflr-peþr) were lengthened. The superior and inferior parts of the spheno-occipiøl synchondrosis (petal-petar, ptsl-ptsr) were normal, while the lateral part of the synchondrosis was increased in height (ptsl- petal, ptsr-petar).

Discussion: The cranial base sutures were abnormal anteriorly and laterally. Medially the

spheno-occipital synchondrosis was deformed. The larger number of abnormal sutural findings

in this patient are reflected by the more severe clinical deformity.

Figure 3.30(q) Z Scores of the Dimensions of the Cranial Base Sutures for Patient IP compared with the 2 Year Old Experimental Standard

Zscore Anterior Cranial Fossa Middle Cranial Fossa Posterior Cranial Fossa 20.00

r 5,00

l0.00

5.00

0.00

-5.00 L_L-L-L !-!-L 9-r-!qL-L o.aLcdd.ØØ-J ØØdclØØ ã. È* Y+ir)a)ô,o- EÉesggsess ,h,h'^XEã-lIFrl-ú F A â\ \ ,åLO.O.r..r U O ñcúF.F.-L= * BÉ EöOÞO¿!r.Ekç E + *Z á iiågÊþËå-iÞ:rÈÈ,¡EËSä: s F F * ää- B.-o.o-

Chopter 3 Pctge 279 3.4.12.13 The craniofacial Dimensions and Angles of patient rp

Dimensions and Angles (Figure 3.30(r)): The facial heights were increased, however the patient's mouth was open, and the findings were not valid. The SNA angle was significantly reduced. (SNB was not valid for reasons stated previously). The cranial base angle (ba-s-n)

was more obtuse. The cranial base dimensions were increased generally.

Discussion: This patient exhibits platybasia of the cranial base, and demonstrates the corresponding reduction in facial angle as a result of the distorted cranial base and the lack of forward projection of the maxilla (see maxilla).

Figure 3.30(r) Z Scores of the Craniofacial Dimensions and Angles for patient rP compared with the 2 Year otd Experimental standard

Zscorc Facial heights Facial Angles Cranial Base 8.00 SNA SNB Angle 6.00 Dimensions 4.00 o 2.00 0.00 -2.00 -4.00 -6.00 -8.00 -10.00 -t2.00 É k ào o E bo bo I Ø I I I ¿ I -o

Page 280 Crouzon Syndrome 3.4.13 Clinical and Radiographic Findings for Patient LW

Clinical Features

Thischildpresented aged 5 years and 6 months (Figure 3.5). There was no family history of

Crouzon syndrome. A sagittal synostectomy had been performed elsewhere when he was 3 months of age. On examination, the calvarial shape was oxycephalic. He had proptosis and hypertelorism. Ptosis of the left eyelid, left amblyopia and astigmatism were also present. Mild bilateral papilloedema was found. He suffered chronic nasal obstruction and had bilateral middle ear effusions and hyponasal speech. Maxillary hypoplasia was evident and he had a class III occlusal relationship.

Lateral, Antero-Posterior and Basal Radiographs

Lateral, antero-posterior, and basal views showed fusion of all sutures with a copper-beaten appearance of the calvaria. The spheno-occipital synchondrosis was patent (best seen on the post-operativeradiographs in Figure 3.5). The sella had an additional depression anteriorly in the region of the jugum sphenoidale. The lesser wings were swept up lateraliy producing the harlequin-mask appearance on the antero-posterior radiograph. The orbits were mildly dystopic with the left lower than the right. The second dentition was appearing in the hypoplastic maxilla.

3D CT Reconstruction

Calvarial bones: The head shape was mildly oxycephalic and scaphocephalic with complete calvarial suture fusion, including the zygomatico-spheno-temporal complex. A bilateral ridge along the sagittal suture was present, possibly a result of the previous craniectomy.

Cranial base: The cribriform plate was thin in the anterior cranial fossa. Small bony defects were seen above the orbits and in the region of the jugum sphenoidale and ethmoid spine. The lesser wings of the sphenoid were swept up and the greater wings were protruding into the orbits. Depression of the jugum sphenoidale anteriorly produced the appearance of double depression to the sella. The spheno-occipital synchondrosis was not visible as being patent on the 3D CT reconstruction. The jugular foramen was prominent on the left side and gave the

Chapter 3 Page 281 impression of a double system due to the notching in the foramen. The right hand jugular foramen was small in comparison.

Orbital: The orbital aperture was not greatly swept up laterally. The junction of the greater wing of the sphenoid with the zygomatic bone (at landmark greater wing laterale) produced a very deep notch. The medial wall and roof of the orbit showed evidence of bony thinning presumed due to endocranial resorption. The inferior orbital rim appeared to be hypoplastic and lower on the left side, compared with the right.

Maxilla: The second dentition was appearing. Hypoplasia of the zygomatic bone and maxilla were identified.

3.4.14 Features of the CT Scan and 3D Reconstruction of Patient LW that made Landmark ldentification difficult

The calvarial landmarks (1, as, br, spt, spc) could not be identified nor reliably estimated. The peri-orbital sutures and cranial base landmarks were identified from the regional bony contours and junctions defined in the landmarks (Figures 3.15-3.26). The areas of bony absence in the region of the ethmoid and orbit did not interfere with the landmark identification.

Page282 CrouzonSyndrome 3.4.15 Results and Discussion of the Quantitative Analysis of Patient L\M compared with the 6 Year Old Experimental Standard

Figures 3.31(a)-(r)

Chapter 3 Page 283 3.4.15.1 The Mandible of Patient LW

Distances (Figure 3.31(a)): Several distances between the adjacent landmarks representing the

outline of the bone were statistically signif,rcant compared with the experimental standard. The

posterior superior body distance (emlil-cbl, emlir-cbr) was increased bilaterally. The left

posterior mandibular notch (mnt-cdl) was also increased.

Dimensions and Angles (Figure 3.31(b)): The only dimension outside the experimental

standard limits was the anterior symphyseal height (gn-id). Similarly the angles were not involved except for the right mandibular notch angle (cdr-mnr-ctr) which was significantly smaller.

Discussion: In Patient LV/ only minor degrees of abnormality of the mandible were found. The increase in anterior symphyseal height may reflect a primary growth abnormality or a secondary growth change to compensate for the class III occlusion. In general the major dimensions and angles, affecting the shape and size of the whole mandible, were not different from the experimental standard and the anterior symphyseal height increase most likely represents a secondary change.

Page 284 Crouzon Syndrome Figure 3.31(a) Z Scores of the Distances of the Mandible for Patient LW compared with the 6 Year Old Experimental Standard

Zscore L R 4.00

3.00

2.00

1,00

0.00

-1.00

-2.00 .o 5 ç ã O I ?YÉ? ÈëëË o = f"-? I E Fi þt rc €TE EB ËåÉë 5 EE vo o

Figure 3.3L(b) Z Scores of the Dimensions and Angles of the Mandible for Patient LW compared with the 6 Year Old Experimental Standard

Zscore Dimensions Angles 2.00

1.00

0.00

- 1.00

-2.00

-3.00 KÈEÞ ,;€! ì-:ÉÊlJ!=.!€!h 40Q) Þ€õ€ Loo ooÐil'ÍÍ or¡o) òoÉ¿ booo.- EE"Ë ä bo 6ò -li=Ei-ts1çEÊF":iJEåË5 E.E:€oõ:i@Ð3" o 'öE

Chapter 3 Page 285 3.4.L5.2 The Maxilla of Patient LW

Distances (Figure 3.31(c)): Multþle distances were significant in this patient. The fronto-

maxillary suture (snml-morl, snmr-morï) was increased in length compared with the

experimental standard. The frontal process of the orbital rim (nlil-morl, nlir-morr) was reduced

in length while the medial infra-orbital rim (orl-nlil, orr-nlir) was increased in length. The

anterior zygo-maxillary suture (zmil-orl) was shorter on the left with a tendency to be shorter on the right (zmir-orr). The lateral maxillary wall height (zmil-emlil, zmir-emlir) was increased bilaterally. The lower pyriform margin (ans-all) was increased on the left side and the upper pyriform margin (all-inml, alr-inmr) was increased bilaterally. The right naso-maxillary suture

(inmr-snmr) was reduced- in length. Increased distances were recorded at the posterior alveolar margin (emlsl-mxtl, emlsr-mxtr), the posterior maxillary wall height (mxtr-msr) on the right, the posterior palatal height (emlsl-gpfl, emlsr-gpfr) and the superior palatal length (ans-pns).

Dimensions and Angles (Figure 3.31(d)): Most distances were within or close to the standard measurements. The anterior midline height of the rnaxilla (na-pr) was significantly increased.

The superior length of the maxilla (msl-inml, msr-inmr) was increased bilaterally. The orbital floor angle (nlil-msl-iobfl) was increased on the left side. The posterior inferior angles of the maxilla (msl-gpfl-emlsl, msr-gpfr-emlsr) were increased. The palatal angle (gpfl-ans-gpfr) was reduced.

Discussion: The measurements in this patient reflect the reduced proportions of the maxilla on the left hand side. The left body and infra-orbital rim of the maxilla, in particular the attachment to the zygomatic bone was smaller than on the right. The alveolar height and postero-lateral wall of the maxilla were conespondingly increased. The midline structures, superiorly, were not significantly different from the experimental standard or were significantly increased. The measurements therefore reflect the clinical appearance of the hypoplastic inferior orbital rim especially on the left, and the relatively normal anterior position of the nasal complex.

Page 286 Crouzon Syndrome Figure 3.31(c) Z Scores of the Distances of the Maxilla for Patient LW compared with the 6 Year Old Experimental Standard

Z Orbital Anterior Lateral Palatal 8 L R L R L R LR 6.00

4.00 ^ 2.00 \ 0.00

-2.OO

-4.00 !x=!!= oo=ââ-bE.h,!ù.h E= EE ã4FãÉÊ :Ê 1i ÉÊ ã É T.9 ñ tõÈ È .!-L qJ J \ * E å ¿.8 e O E? ë I é d5 È È -¿Er¡ g. E= H 2 h EÈ E ø E Nã c dE N.g É d F üEù,È :å Ë co= cÐ N ËÊÉE EÐ

Figure 3.31(d) Z Scores of the Dimensions and Angles of the Maxilla for Patient LW compared with the 6 Year Old Experimental Standard

Z score Dimensions Angles 7.00 6.00 5.00 4.00 3.00 2.OO 1.00 0.00 -1.00 -2.OO -3.00 +3þZE=EÈá.\Er:cÉËïhsçft8h-?ij ¡Ð bPÈP+ Èa l¿9V ¿l -gtEË.¿Ë+zãbÊR Øói¿ ;ÉçÉc cÀ ãbøqHEñoñ !FÈd Eoooo l¿úú EE de cÉ 7223e.-ìè\ ÉE J+ L îî lcÉõñ:tsEcc

Chapter 3 Page 287 3.4.15.3 The Nasal Bones of patient LW

Distances (Figure 3.31(e)): The length of the nasal bone (na-n) medially was at rhe upper limit of the experimental standard range. The length and width of the nasal bone was decreased on the right hand side (inmr-snmr, snmr-n).

Dimensions and Angles (Figure 3.31(e)): The superior width of the nasal complex (snml-snmr) was decreased. The angle of the nasal bones from the cranial base (s-n-na) was increased as

was the splay of the nasal bones (inml-snmVsnmr-inmr).

Discussion: The nasal bones were generally reduced in size. The deformity was more pronounced superiorly a¡rd laterally. The small bones were compensated for in size by the

midline projection of the nasal complex. The nasal bones were anteriorþ placed (see maxilla)

and with an increased angle of projection.

Pøge 288 Crouzon Syndrome Figure'3.31(e) Z Scores of the Measurements of the Nasal Bones for Patient LW compared with the 6 Year Old Experimental Standard

Z Distances R Dimensions Angles 4 L

3.00

2.00

1.00 0.00

-1.00 -2.00

-3.00

-4.00 É , d ñ E E E E tr ÊE É É tr d d ! H E .= ÉH

Chapter 3 Page 289 3.4.15.4 The Frontal Bone of patient LW

Distances (Figure 3.3 1 (f)):

Supra-orbital Region: Medially the fronto-nasal suture (n-snml, n-snmr) showed a trend to be

reduced on the left and was significantly reduced on the right side. The fronto-maxillary sutures

(snml-morl, sntff-molr) were significantly increased.Increased distances were also recorded at

the superior medial orbital rim (sorl-slorl, sorr-slorr) and in the region of the anterior fronto-

zygomatic suture (slorl-2fl, slorr-zfr). The right superior lateral orbital rim (sorr-slorr) was

decreased.

Ethmoid Attachment: The projection of the nasal root from the foramen caecum (n-fc) was

reduced. The frontal ethryoid attachment length (cpal-cppl, cpar-cppr) was increased at the level

of the cribrifonn plate with decreased distances in the width of the attachment (cppl-ofaml, cppr-ofamr) and in its length in the orbital region (morl-ofaml, morr-ofamr) where it attaches to the lateral plate.

Sphenoid Attachment: The width or length of the superior orbital fissure (ofami-sobfl, ofamr- sobfr) was decreased on the left with a similar trend seen on the right. The lesser wing length

(spal-cppl, spar-cppr) was increased on the right with a similar trend found on the left side. The parietal attachment (spc-br) and sphenoid attachments (zfs-spc and spc-spa) were not recordable due to the fusion of sutures and hence poor visibility of landmarks in this region.

Dimensions (Figure 3.31(Ð): The anterior prominence of the frontal bone was within the normal range (s-g) and the depth of the anterior cranial fossa (sorl-spal, sorr-spar) was not significantly different from the experimental standard. The anterior superior orbital width of the frontal bone (sorl-sorr), the antero-lateral superior orbiøl width (slorl-slorr), and the posterior width (spal-spar) were all significantly increased compared with the experimental standard.

Discussion: The fronto-maxillary sutures were increased in length and may contribute to displacing the orbits laterally. In addition the fronto-zygomatic suture was increased in length, and was related to the fusion of the of coronal sutures extending down into this region. A lesser severe abnormality was seen at the sphenoid lesser wing.

Page 290 Crouzon Syndrome N è|.JONÀO\tt 9.F oq uu9999 OOOOOO O(D O'O n-snml (, I snml-morl :-e (¿J morl-so¡l sorl-slorl t- ä'G slorl-2fl zfl-zfsl FN zfsl-slorl tu2 n-snmr oo snmr-morT 9ã5u) InOfT-SOIT F sor¡-slorr Ëo ttà I ã slorr-zfr I (D I È5 zf¡-zfsr I I zfsr-slorr I 1(D I I n-fc 4 - ct) I fc-cpal I I oã cpal-cppl I t- cppl-ofaml FI o\8 morl-ofaml ts aDi o fc-cpar È cpar-cPPr OU cppr-ofamr È3 morr-ofamr !o I ofaml-sobfl I Xh sobfl-zfsl t- U) 'Ó Xã spal-cppl ts. Ct) CD ofamr-sobfr o oE Þ- sobfr-zfsr ô spar-cppr -¡t \D ?4 ß g-n Ê9ã ì s-g U sorl-spal Ê9 l+ sorr-sPar o \ so¡l-sorr Ø slorl-slorr tÉ spal-spar Ø NJ \o o 3.4.15.5 T}l.e Zygomatic Bone of Patient LW

Distances (Figure 3.31(9)): The spheno-zygomatic suture length (zfsl-gwll, zfsr-gwlr) was reduced on the left with a tendency to be reduced on the right. The anterior fronto-zygomatic suture (slorl-2fl, slorr-zfr) distance was increased bilaterally. The height of the lateral orbital wall (lorl-slorl, lorr-slorr) was increased, with a reduced height of the frontal process of the zygomaticbone (zfl-ztl) on the left. The zygo-maxillary suture (zmil-orl) was decreased on the Ieft.

Dimensions (Figure 3.31(g)): No significantly different dimensions were measured

Discussion: The length gf the fronto-zygomatic suture v/as clearly abnormal. Fusion at this suture would be expected to reduce the vertical growth of the bone. The overall height of the zygomatic bone was within the limits of the experimental standard with the height of the lateral orbiøl rim being increased but the lateral frontal process reduced in height. A reduction in length of the zygo-maxillary suture was found and was related to the hypoplasia of the infra- orbital rim of the maxilla. Suture fusion, found qualitatively at the frontal, parietal and sphenoid junctions, also holds the zygomatic bone and lateral orbital wall posterior relative to the medial structures

Figure 3.31(g) Z Scores of the Distances and Dimensions of the Zygomatic Bone for Patient LW compared with the 6 Year Old Experimental Standard

Distances 4.00 Dimensions

3.00 L R

2.00

r.00

0.00

-1.00

-2.00

-3.00

-4.00 '= .= EE=EFEEEEFEEE ËËËE*åE5EiE:E ttsôôuoç ç ! ç .9ÞoÐ?+N='ìõ-lo.ñ-l i f + È=r EERçåtËEE**ËË e 3.E"Ë Ëä*t;tsËË*å[Ë -ÞØ-¿;wÐ 5

Page292 CrouzonSyndrome 3.4.15.6 The Vomerine Bone of Patient LW

Distances. Dimensions and Angles (Figure 3.31(h)): The palatal distance (ans-pns) was increased compared with the experimental standard. The longitudinal dimension (h-ans) was not significantly different from the experimental standard. The angle of the vomer relative to the cranial base (s-n/h/ans) was significantly decreased.

Discussion: The vomer showed some variation in this patient but remained close to normal limits. The decreased angle of the vomer was related to the medial prominence of the naso- maxillary complex (see maxilla) and may have partly resulted from the cranial base deformity in this patient, where the cranial base angle was found to be reduced (see craniofacial dimensions and angles).

Figure 3.3L(h) Z Scores of the Measurements of the Vomer for Patient LW compared with the 6 Year Old Experimental Standard

Z score Distances Dimension & Angle 5.00 4.00 3.00 2.O0 1.00 0.00 -1.00 -2.00 -3.00

?Íú'õ? 6 (d ?3,tîf I I a>>86.-cú'õ € ØI

Chapter 3 Page 293 3.4.L5.7 The Ethmoid Bone of patient LW

Lateral Ethmoid Plate (Figure 3.3I(i)):

Distances: The majority of lateral ethmoid plate distances forming the medial orbital wall, that

were measured, were reduced. The anterior border of the lateral plate (nlil-morl, nlir-morr) was

reduced in height and the orbital length of the frontal ethmoid attachment (morl-ofaml, morr-

ofamr) was reduced bilaterally. The height of the posterior border of the lateral plate (ofamr-

msr) was also reduced on the right. The exception was the junction with the maxilla at the inferior border of the Lateral plate (msl-nlil, msr-nlir) which was increased on the left and showed a similar trend on the right. The posterior frontal ethmoid attachment (cppl-ofaml, cppr- ofamr) was reduced, witþ a tendency for an increased width anteriorly (morl-cpal, morr-cpar).

Dimensions and Angles: The inter-orbital dimension (morl-morr) and the dimension between the optic canals (ofaml-ofamr) were significantly increased. The splay of the lateral plates (msl- ofamVofamr-msr) was reduced posteriorly.

Page 294 Crouzon Syndrome Figure 3.31(i) Z Scores of the Measurements of the Lateral Ethmoid Plate for Patient LW compared with the 6 Year Old Experimental Standard

Z score Distances Dimensions & Angles 5.00 Medial orbital Frontal ethmoid attachment 4.00 -___--t L B.

3.00

2.00

1.00

0.00

-1.00

-2.00

-3.00

-4.00 '-='ã= ãEa'4 jçE?Ê"8 çç ßã ß.ã TiEEÌT ES E ú +õ Èç ç=Þtotr ãEEH ËF"EH 9ÊE.q Éo E- ËE 9Þ.-ti H.ã:õ oÉÉà

Chapter 3 Page295 3.4.15.7 The Ethmoid Bone of Patient LW (continued)

Cribriform Plate (Figure 3.31O):

Distances: The spheno-ethmoid synchondrosis (es-cppl, es-cppr) was increased in width. The

length of the plate was increased bilaterally (cpal-cppl, cpar-cppr).

Angles: The lateral angle of the cribriform plate compared with the nasion - sella line (s-n/cpar-

cppr) was significantly increased on the right. The medial angle of the cribriform plate (n-s/es-

fc) was reduced suggesting depression of the cribriform plate.

Medial Ethmoid Plate (Figure 3.31(j)):

Distances: The distance from the nasion to foramen caecum (n-fc) was decreased with the

remainder of the measûrements of the medial plate not significantþ different from the

experimental standard.

Dimensions: The dimensions were not significantly different from the experimental standard.

Discussion: The lateral plate was reduced in height and in superior length. The cribriform plaûe

was increased in length but was depressed, while the medial plate was relatively normal.

Anteriorly, the inter-orbital distance was increased and posteriorly the spheno-ethmoid

synchondrosis was widened. The pattern of distortion of the ethmoid was of a reduced orbital

component with a broadening and an increased length of the cribriform plate. This fits with the

clinical appearance of a predominant orbital volume and rim deficit with hypertelorism, with a

reasonable midline protrusion.

Page296 CrouzonSyndrome Figure 3.31(i) Z Scores of the Measurements of the Cribriform and Medial Ethmoid Plates for Patient LW compared with the 6 Year OId Experimental Standard

Z score Cribriform plate Medial plate 5.00 Distances Distances Dimensions 4.00 L R 3.00 2.00

1,00

0.00 -1.00

-2.00

-3.00 Lk! Ê -() Þo () o I (.) o ÉÞ.o. E Ë.e I ryÇ I I t¡ o. o. I c) EEE 9()() 83f? HOöòo Ø Ø C) .f¿ES .óL¿ () I *orÊ.Ë Èì F0) 9(J ÉÉtt

Chapter 3 Page 297 3.4.15.8 The Sphenoid Bone of Patient LW

Lesser'Wing (Figure 3.3 1(k)):

Distances: All the distance measurements of the lesser wing (ofaml-acl, ofamr-acr, acl-sp al,acr- spar, spal-es, spar-es) were increased bilaterally compared with the experimental standard.

Dimensions and Angles: The dimension between the tips of the wings (spal-spar) was increased. The angle of the lesser wings (spal-es-spar) was not significantly different from the experimental standard, while the splay of the lesser wings from the midline (n-s/acl-spal, n- s/acr-spar) was significantly increased bilaterally.

Pter)¡goid Plate (Figure 3.3 I (k)):

Distances and Angles: The distances of the pterygoid plate were not significantly different from the experimental standard. The axis of the pterygoid plates (n-s/ptsl-hpl, n-s/ptsr-hpr) was significantly decreased bilaterally, implying they were angled more medially and/or anteriorly from the midline than the controls when measured from the nasion-sella line.

Greater Wing (Figure 3.31(l)):

Distances: The spheno-zygomatic suture (gwll-zfsl) and the superior orbital fissure length

(gwml-sobfl) were reduced on the left side compared with the experimental standard. A tendency for these distances to be reduced on the right side was also seen. Landmarks on the squamous sphenoid bone (spt and spc) could not be identif,red bilaterally, due to fusion of the calvarial bone in this region and hence the distances of the lateral part of the bone could not be measured. The posterior floor of the greater wing was increased in length (fosl-petal) adjacent the spheno-temporal suture on the left side.

Dimensions and Angles: While the angles of protrusion of the greater wing were increased

(zfsl-gwmUgwmr-zfsr and gwll-gwml/gwmr-gwlr), the angle of splay of the greater wing relative to the floor (zfsl-gwml-ptsl, zfsr-gwmr-ptsr) was decreased. The posterior angle of the greater wing (fos1-petaVpetar-fosr) was normal.

Page 298 Crouzon Syndrome (n ìã FÉ u)I I (, (.¡¡ ^N It N (Þ .O-J Yø è¡..JOl.JèO\oÒ Ø b b bbbbbbb c) .< ral O O O Aoa OOOOOOO o uvù =8o ä v UY Éô -. Lr fosl-gwll I ofaml-acl I I È4 - â,(, (Þ zfsl-gwll - x¿È acl-spal t' J(, Ê9 åtJ o spal-es U (! i-r Ø I 9^ ts fbsr-grvlr o Þ) Frà v ÞN c) zfsr-gwlr ofamr-acr Øo -(D \tìr(n ãN acr-spar F oØ (h? t; ã (¿ gwll-grvml spar-€s - v ôE { (ÞXÈ gwml-sobfl oa !5õ - J Lr o o sobfl-zfsl spal-spar x=.ol¿ Ël o Ø ìõq:Ps + È>.to spal-es-spar - grvlr-gwru ¿È n-s/acl-spal ãã.D R" tlFú>ãÀ¡È grvru-sobfr F ä(t n-s/acr-spar á;ô oc P:P sobfr-zfsr o gu) 5(D Ø rD qhñ o\9 =¡ \lrfDYLx fosl-ptsl ptsl-hpl È<=¿=t l- FÚ (Þ fosl-petal o Þlo hpl-hnl Pô1 Ø ó9ç') CD r< - hnl-ptll -9 Fñ o U5 ìõ n F- D¡ fosr-ptsr ptll-fool =o Ø (!=ã¡+ fosr-petar l=l l.] Þ È(e I X: oc) 4L rã i5 Ø ptsr-hpr o ã(D n ì+ th fosl-fosr )tD hpr-hnr ùe H o 3 o á c0 S zfsl-gwml-ptsl È \ Ø e€ hnr-ptlr r{ (\ o zfsr-grvmr-ptsr ptlr-foor Þ¡ o\ i' t{ Ø Éûa o zfsl-grvml/gwru- (no zfs' þ (DÞ grvll-grvml/gwmr- Ê¡x oa ¡t= 'Þ grvlr n-s/ptsl-hpl f I ùq o ùa I CD c\ fosl-petal/petâr-f osr I F(D n-s/ptsr-hpr o I I I ã NJ È \o ù 3.4.15.8 The Sphenoid Bone of patient LW (continued)

Body of Sphenoid (Figure 3.31(m)):

Distances: The majority of the body distances were larger than the mean of the experimental

standard. The inferior lateral length (gwml-ptsl, gwmr-ptsr) was increased along with the lateral

height of the spheno-occipital synchondrosis (ptsl-petal, ptsr-petar) bilaterally. The anterior

body had increased distances at the spheno-ethmoid synchondrosis (es-cppl, es-cppr). The

posterior frontal ethmoid attachment (cppl-ofaml, cppr-ofamr) was reduced in length with a

corresponding increase in distance to the greater wing mediale (ofaml-gwml). The measured

distances of the floor and sella were not significantly different from the experimental standard. Dimensions and Angles: -V/hile the anterior inferior width of the body (gwml-gwmr) was within

the experimental standard, the measurement between the anterior optic foramina was increased

(ofaml-ofamr). The superior spheno-occipital synchondrosis (petal-petar) was normal. The

height of the posterior clinoidprocesses was increased on the left side (ptsl-pcl). The angles of

the body from the midline were normal. The angle of the floor of the sphenoid body (es-ves-h)

was more acute

Discussion: This sphenoid bone in this patient was abnormal in most areas. The lesser wings were elongated with greater protrusion of the lesser and greater wings. Medially, the spheno- ethmoid synchondrosis was lengthened. The pterygoid plate was splayed anteriorþ and medially. This position may account for the relatively prominent midline facial structures (see maxilla and nasal bones). The deformity was also present posteriorly, in particular, in the region around the spheno-occipital synchondrosis and the sphenoid body was enlarged. The findings were consistent with a mixed pattern of sutural involvement and the effects of raised intracranial pressure on the size of the sphenoid body.

Page 300 Crouzon Syndrome Figure 3.3L(m) Z Scores of the Measurements of the Body of the Sphenoid for Patient LW compared with the 6 Year Old Experimental Standard

Z score Lateral/posterior Anterior Sella Baseifloor Dimensions Angles 5.00 L RLR LR 4.00

3.00

2.00 1.00 -AB--- 0.00

-1.00

-2.00

-3.00 !!: -=áLlb b Ës tØøód üéÈ ,e 8" HOao +988. Fb-ËËE'.5F g å9P 9-l O., 3E-¡ ?oU 9iç b TT E-r-þ-& å gåå Ol4 ãï ÉÉ O- d Ê aÉ dH i -O1 5 EE E d€. = ËH * 6o.!i.a. ååã SE È¿ù eo O,P 5 F-e -04 oã òoE t i;;

Chapter 3 Pctge 301 3.4.15.9 The Temporal Bone of patient LW

Distances (Figure 3.3 1(n)):

Squamous Temporal Bone: The temporal squamous bone was not fully measurable in this chitd

due to lack of visibility of the asterion (as) a¡rd sphenion (spt). The medial mastoid height (mal-

smfl) was significantly increased on the left compared with the experimental standard.

External Auditory Meatus: The lateral mastoid prominence (mal-eamil, mar-eamir) was

increased bilaterally. The configuration of the external auditory meatus was symmetrical with

decreased distances of the superior anterior rim on the right (por-eamar) with a similar trend

seen on the left.

Zygomatic Process: The zygomatic process had symmetrical pattern profiles, where the length

of the zygomatic arch (ztl-aul) decreased on the left with a similar tendency on the right. The

articular fossa height (afl-ael, afr-aer) was normal.

Petrous Temporal Bone (Figure 3.31(o)): The sphenoid-petrous temporal suture (fisr-petar)

was increased in length on the right with a tendency to be increased on the left. The right jugular foramen width was naffowed (flr-jfmr) with a similar pattern profile seen on the left.

The inferior occipital mastoid suture distance (mal-jflI, mar-jflr) was increased bilaterally, along

with the left medial temporo-occipital suture (inferior) (frnl-ptsl).

Dimensions and Angles (Figure 3.31(o)): The petrous temporal ridge dimension (petal-petpl, petar-petpr) was increased bilaterally. The dimensions between the temporal bone were normal.

The angle of the zygomaprojection (petal-au1-ztl, petar-aur-ztr) was normal, as were the angles of the auditory canal (pol-iamViamr-por) and the petrous temporal bone (petpl-petaVpetar- petpr).

Discussion: The mastoid process was prominent with minimal symmetrical deformity of the external auditory meatus. The length of the zygomatic process was decreased and may be related to fusion of surrounding squamous sutures. Sutures around the petrous temporal bone were increased in length producing some lengthening of the petrous temporal bone with narrowing of the jugular foraminae. This was a common finding for this region in the patients studied.

Page 302 Crouzon Syndrome Figure 3.31(n) Z Scores of the Distances of the Temporal Bone for Patient LW compared with the 6 Year Old Experimental Standard

Zscore Squamous External Auditory Meatus Zygomatic Process 6 L R L R L R 5

J ______a_

-1

-J ÈkL! çk!çç LF!KÈ eødç :ø6q .=Êod'= O.ô d çoÊpó çok!á 1E E Eç H F OÉ Ë =EtroÊÞ = lËtq f f 3 3.r i f 3.3. f !g¿ Ë dGlis 'I â?E 8 E åE õEåFË É ñ q Ë' €çLÊ É 383ã ËÉ E+ ã ã E õ 9Ë E È *E ! o Ëtroatrdd trtroÀtr oo ddoo

Figure 3.31(o) Z Scores of the Measurements of the Temporal Bone for Patient LW compared with the 6 Year Old Experimental Standard

Zscore Petrous Dimensions Angles 9.00 L R L R

7.00

5.00

3.00

l 00

-1.00

-3.00

-5.00 d d.- d s.+'d s qE9¡? q-LlÈ fiT9¿ aÊzz ts-¡iìr ï!!t- ¿':tåP+ -[fi8.äÊ-E Êo-- -l d Àl É'bii Ê¡dd .9õts'á ËÉ8.3 E E'.E 3 *o *od ËÉËP"'EÊ dd 8, 8, '- Eèts-8. .:d oõ- Ol È À

Chapter 3 Page 303 3.4.15.10 The Parietal Bone of patient LW

Distances: The key landmarks for the parietal bone for Patient LW were not visible due to

suture fusion and could not be reliably estimated. Therefore the parietal bone was not measured

and a pattern profile of Z scores was not generated. The measurement data for the experimental

standard are reported in Appendix2.

3.4.15.11 The Occipital Bone of Patient LW

Distances (Figure 3.31(p)): The distances measured on the occipital bone and the foramen magnum were not significantly different from the experimental standard except for the medial temporo-occipital suture (inferior) (fml-ptsl), which was increased in length on the left with a similar tendency on the right. The inferior spheno-occipital synchondrosis was not significantþ different (see sphenoid and cranial base sutures for other distances.

Dimensions (Figure 3.31(p)): The dimensions were not significantly different from the experimental standard.

Discussion: The measurements of the occipital bone were abnormal along the suture with the temporal bone. Qualitatively, the lambdoid sutures were fused.

Figure 3.31(p) Z Scores of the Distances and Dimensions of the Occipital Bone for Patient LW compared with the 6 Year Old Experimental Standard

Z score Distances 4.00 Dimensions L R 3.00

2.00

1.00

0.00

-1.00

-2.00 o..lj 0 o fr aÀ ã.E E I EE 'ibËb.Eþ 'i :t1 q-ì O. =ts ts L (d 9ô- oo j.¡ïi:ti ? or - Èq) E 'To ri ¡ I -r J. qúG.ÈH - ãÉ,8É Ø .iE¿È o.È o¡ o, '-.Hq '-Hç or -o -o orJ '- ¡- .E aÈ

Page 304 Crouzon Syndrome 3.4.15.L2 The Cranial Base Sutures of Patient L\ry

Anterior Cranial Fossa (Figure 3.31(q)): The spheno-ethmoid synchondrosis (es-cppl, es-cppr)

was increased in length along with the spheno-frontal suture (cppl-spal, cppr-spar) in the

anterior cranial fossa. In the orbit, the suture was normal and the spheno-zygomatic suture

(zfsl-gwll, zfsr-gwlr) was reduced in length.

Middle Cranial Fossa (Figure 3.31(q)): The sutures were relatively normal with a posterior

increase in length of the right spheno-petrous temporal suture (fisr-petar).

Posterior Cranial Fossa (Figure 3.31(q)): The left medial temporo-occipital suture (inferior)

fifml-ptsl) and the occipiøl mastoid sutures (superior) (flI-petpl, jfu-petpr) were significantly increased. The superior and inferior parts of the spheno-occipital synchondrosis (petal-petar,

ptsl-ptsr) were normal, while the lateral part of the synchondrosis (petal-ptsl, petar-ptsr) was

increased in height.

Discussion: Many abnormal measurements were found in the cranial base in this patient.

Anteriorly, significant involvement was seen medially while posterioriy the temporal bone was

involved laterally and the spheno-occipital synchondrosis deformed medially.

Figure 3.31(q) Z Scores of the Dimensions of the Cranial Base Sutures for Patient LW compared with the 6 Year Old Experimental Standard

Z score Anterior Cranial Fossa Middle Cranial Fossa Posterior Cranial Fossa 6.00 5.00 4.00 3.00 2.00 1.00 0.00 -1.00 -2.00 -3.00 L d L L-ç-L LHL-LLL-L ØØd.dØØ dõÞ.äïïiÈÈo.ô_cd¿d.Ø_¿r=-- EÉee.ssgess ????'ileobo .-ùo.o.r.r-Y()0)o.o. ò,h-=rEãJ'l \iJLØØ u o Ë Ë * 9q? ,P iiåiËf-i¿'-iiñõHHH õäqØÑÑ f"ãoÉ#€€ ;riì,¡€FËSäs8 xx(.)o.o. o'

Chapter 3 Page 305 3.4.15.13 The craniofacial Dimensions and Angres of patient LW

Dimensions and Angles (Figure 3.31(r)): The facial heights were increased, however the patient's mouth was open during the CT scan and the measurements were not valid. The SNA angle (s-n-ss) was normal and the SNB angle (s-n-sm) was not valid. The cranial base angle

(ba-s-n) was more acute in this patient. The cranial base dimensions were not significantly different from the experimental standard, with a tendency for the clivus to be lengthened (b-s).

Discussion: The cranial base angle was reduced in this patient. The SNA angle was normal and reflects the midline projection of the naso-maxillary complex. Therefore the medial orbital wall was prominent, however, the lateral orbital wall was deficient, influenced by the lateral calvarial suture fusion.

Figure 3.31(r) Z Scores of the Craniofacial Dimensions and Angles for patient LW compared with the 6 Year old Experimental standard

Zscorc Facial heights Facial Angles Cranial Base 4.00 SNA SNB Angle Dimensions 3.00

2.00

1.00

0.00 Þ-- -1.00

-2.00

-3.00 -4.00 ^ k Éøé ào o Ë I I bo Òo Ø I I .t,li É ,l .o -o .o

NB: Supramentale (sm) not accurate due to open mouth of patient.

Page306 CrouzonSyndrome 3.4.L6 Clinical and Radiographic Findings for Patient AY

Clinical Features

This patient f,trst presented aged 5 years and 5 months with a mild form of Crouzon syndrome

(Figure 3.6). There was no family history. A ventriculo-peritoneal shunt had been inserted elsewhere as an infant. The calvarial shape was turricephalic and he displayed mild proptosis, hypertelorism and had a divergent squint. The nasal septum was deviated and the mærilla was hypoplastic with a class 3 occlusal relationship.The palate was described as being high and arched. There was no evidence of upper airway obstruction however his speech was hypo- and hypernasal with articulation difficulties. There was no functional indication for surgical intervention and the patient was under annual review.

Lateral and Antero-Posterior Radiographs

The lateral and antero-posterior radiographs demonstrated the shunt in situ. A mild oxycephalic head shape was seen with a very mild copper-beaten appearance of the calvaria. The coronal sutures appeared to be faintly visible inferiorly. The other sutures were not seen. The spheno- occipital synchondrosis was patent. The lesser wings of the sphenoid were swept up laterally.

Hypertelorism was associated with broad ethmoid and maxillary sinuses. The second dentition was emerging.

3D CT Reconstruction

Calvarial bones: A faint outline of the coronal sutures was present otherwise all sutures were fused.

Cranial base: The lesser wing of the sphenoid appeared to be short in its lateral projection.

Protrusion of the greater wing of the sphenoid into the orbit was noted. The middle cranial fossa was unremarkable. The spheno-occipital synchondrosis was not visible. The foramen magnum was long and pointed posteriorly.

Orbital: The shape of the orbital aperture was somewhat ovoid in the horizontal axis. Mild medial and lateral wall bulging was noted. The zygomatic bone and orbital rim were underdeveloped. The left external auditory meatus was hidden by the zygomatic arch.

Chapter 3 Page 307 Maxilla: The maxilla was nanow and short.

3-4-L7 Features of the CT Scan and 3D Reconstruction for Patient AY that made Landmark Identification difficult

The infra-orbital foramen could not be identified. The calvarial landmarks (1, as, br, spt, spc)

could not be identified nor reliably estimated. The peri-orbital sutures and cranial base

landmarks were identified from the regional bony contours and junctions defined in the

landmarks (Figures 3.15-3 .26).

Page 308 Crouzon Syndrome 3.4.18 Results and l)iscussion of the Quantitative Analysis of Patient AY compared with the 6 Year Old Experimental Standard

Figures 3.32(a)-(r)

Chapter 3 Page 309 3.4.18.1 The Mandible of Patient AY

Dist¿nces (Figure 3.32(a)): The anterior superior body length (id-emlil, id-emlir) was

significantly reduced compared with the experimental standard while the posterior superior

body length (emlil-cbl, emlir-cbr) was increased bilaterally. This may be accounted for by an

anterior position of the first molar tooth. The left anterior ramal length (cbl-ctl) was reduced.

Dimensions and Angles (Figure 3.32(b)): The dimension of intermolar distance (em1i1-emlir)

was significantly reduced consistent with the anterior placement of the first molar in this patient.

The left inferior ramal distance (gol-cbl) was increased and the anterior symphyseal height (gn-

id) was increased. The left and right gonial angles (cdl-gol-gn, cdr-gor-gn) were significantly

increased.

Discussion: The flust molar was anteriorly placed in the dental arch accounting for many of the

significant findings. The anterior symphyseal height was increased and probably represented a

compensatory growth change due to the occlusal relationship (see Patient LV/). The pathogenesis of the increased gonial angles is unclear, however, disturbances in maxillary growth or muscle forces may be implicated.

Page 310 Crouzon Syndrome ttll I I I ôuj\u)ñ+OÈf.Jurè N (¡ (JJ u) Ur N ¡ Ø oa 'o Ø ^-¡ OOOOOOOOOQA o c) 0a a u I I I s ä ã O OO O O o (D rr(D õ ã I I o gol-gor id-em1il åP I I (, ã' (, I cdl-cdr X r.J ¿e emlil-cbl O¡.) cbl-cbr E 'Þ. emlil-emlir ¿-N id-cbl rì HN 5 ou) (D CD È(n cdl-ctl =ô cbl-ctl tl Ø t- gol-cbl rf ìÁ Fr (Þ Èoô ctl-mnl 5(Â cdr-ct¡ Ë:i gor-cbr mnl-cdl tD

€\if (D cdl-gol gn-id (Dx (D\J

gn-cdl O\ rì gol-gn Ë3 gn-cdr rD ^P =' Êä lrl ct) 'ut x!L \J !) id-em1ir (DFt cdl-mnl-ctl (J { emlir-cbr I XT ='tD cdr-mnr-ctr I Ëz (D0e cdl-gol-gn tØ¡i. ô id-cbr Ê¡I cdr-gor-gn (n= cbr-ct r+= ctl-cbl-id ùc 5B À¡ l! o Â¡ (+ -5 È !lã ô ctr-cbr-id cno cü-mnr € ctl-cbl-emlil s? ÈFú cÈ mnr-cd¡ Þ ì ctr-cbr-em 1 ir ({ (D gol-gn-id cdr-gor gor-gn-id (Þ

Oa gor-gn (\ gol-gn-gor ({ ã 3.4.18.2 The Maxilla of Patient Ay

Distances (Figure 3.32(c)): The left fronto-maxillary suture (snml-morl) was increased on the

left and the medial orbital floor and the anterior border of the lateral ethmoid plate (nlil-morl,

nlir-morr) was decreased bilaterally. The posterior lateral orbital floor distance (msl-iobfl, msr-

iobfr) (bilateral) and the maxillary infra-orbital rim (orl-nlil, orr-nlir) were increased. Increased

distances were recorded at the lateral maxillary wall (zmil-emlsl, zmir-emlsr) with decreased

distances anteriorly along the anterior alveolar margin (emlsl-pr, emlsr-pr). The left upper

pyriform margin (all-inml) was increased. The posterior alveolar margin (emlsl-mxtl, emlsr-

mxtr) was increased bilaterally, the posterior maxillary wall (mxtr-msr) was increased on the

right and the posterior l4teral orbital wall (msl-iobfl, msr-iobfr) was increased bilaterally. The

posterior palatal height (emlsl-gpfl, emlsr-gpfr) was also increased and the posterior palatal

width (gpfr-pns) was also increased on the right.

Dimensions and Angles (Figure 3.32(d)): The posterior height of the right maxilla (gpfr-msr)

was increased along with the superior length of the maxilla (msl-inml, msr-inmr). Other

dimensions measured were normal. The orbital floor angle on the left (nlil-ms1-iobfl) was

increased. The left posterior inferior angle of the maxilla (msl-gpfl-em1sl) was also increased.

The palatal angles were normal.

Discussion: This patient had similar features to Patient LW \l/ith slight asymmetry to the

maxilla. The left maxilla was smaller than the right at the orbital level. The orbital distances

reflected broader well-developed inferior and medial orbital rims and this conelated with the

milder degree of clinical deformity. The first maxillary molar was situated anteriorly in the

maxillary arch in a similar manner to the molar in the mandibular arch.

Page 312 Crouzon Syndrome trtÊ N ãJ ttt (¡ \O U)tJOtJrrA(JrO\ Ln U) UJ -¡ o tal OQ bb õb bb b bb b bõbbbbbbb ão OOOOOOOOOO OOOOOOOOO o 0e snml-morl 'v ô o¡l-iobfl A' (!ã nlil-morl t !L (, iobfl-gwll msl-nlil I (, msl-iobfì 9¿È zfsl-gwll - 1.,¿ tù orl-iobfl =. zfsl-slorl Ol\)¿ì orl-nlil d slorl-2fl snm-mon zfl-zfsl !, nli¡-mon êN o¡l-ilorl rf< ãN msr-nlir F 5U) Èu) msr-iobfr rrõ x ilorl-lorl on-iobfr ÞE lorl-slorl {Ê on-nli¡ bã Èã8 zf7-ztl 'v, zmil-orl ztl-parl =ô Frà zmil+nlsl { pa¡l-zmil CD l.rl emlsl-pr I I t' zrnil-orl U ans-all '(!+l' Ø all-inml Þ Þ inml-snml CD 5r- ô (Dr I I a oY. or¡-iobfr o \J I I o !¡ I o\Ë iobfr-gwlr ã -rtt' zm-o[ (D zrni¡-emlsr I zfsr-gwlr ÂV, og em I sr-pr zfsr-slorr ans-alr Àã ã' Èô o ã: H Ctt al¡-inmr slorr-zfr \^l Inff-sm zft-zfsr XA ^u) F (D pr-ans or¡-ilor¡ ÞrÈ ilorr-lorr emlsl-ffitl rã mtl-msl - ¡>ãã lor¡-slor¡ 9> msl-iobfl l- ãoa zfr-ztr =.È iobfl-zmil 5(D zlr-pafi Þ.i (D ¡.¡ U) (Þ pa¡f-zmlr (t) emlsr-mxtr F.f Þ= nE-msr Â¡ zffilf-off 5 Frà msr-iobfr iobfr-zmi¡ (t) Ë Fç slo¡l-zmil S I \ emlsl-gpfl I åF (\ Pz)È slor¡-zmir \ gpfl-pns U ({ ÊÂ¡ parl-orl !1 o Ê¡x o emlsr-gpfr - palf-off Ø gpfr-pns ;'t-P Þ gwll-ilorl o I È gwlr-ilorr Ø Oa ans-Pns F : oFl ({N ({ 3.4.18.3 The Nasal Bones of Patient Ay

Distances. Dimensions and Angles (Figure 3.32(e)): The nasal bones were not significantly different from the experimental standa¡d with the exception of the right sided fronto-nasal suture (n-snmr) which was increased in length. The dimensions and angles measured were not significantly different from the experimental standard.

Discussion: There was minimal abnormality with regard to the distances and dimensions and angles of the nasal bones in this patient. This conesponded with the mild clinical deformity.

Page 314 CrouzonSyndrome Figure 3.32(e) Z Scores of the Measurements of the Nasal Bones for Patient AY compared with the 6 Year OId Experimental Standard

Z score L Distances R Dimensions Angles 6.00 s.00 4.00 3.00 2.00 1.00 t 0.00 -1.00 -2.00 É H H H d E d Ef E E tr E É tr E É É É^i 6 É d Ê d fE E tr tr ÉE .Eã Ê c

Chapter 3 Page 315 3.4.L8.4 The Frontal Bone of Patient AY

Distances (Figure 3 .32(Ð):

Supra-orbital Region: The fronto-maxillary suture (snml-morl) was increased on the left. The anterior fronto-zygomatic suture (slorl-2fl, slorr-zfr) was increased bilaterally. The right fronto- nasal suture (n-snmr) was increased.

Ethmoid Attachmenf The measurements of the ethmoid atûachment were not significantly different from the experimental standard.

Sohenoid Attachment: The length of the superior orbital fissure (ofaml-sobfl) was reduced on the left side. This was not compensated for by an increased lateral distance of the fronto- sphenoid suture (sobfl-zfsl). The length of the lesser wing was reduced (spal-cppl, spar-cppr).

The parietal attachment (spc-br) and sphenoid attachments (zfs-spc and spc-spa) were not recordable due to the fusion of sutures and hence poor visibility of landmarks in this region.

Dimensions (Figure 3.32(f)): The dimensions demonstrated reduction in the glabellar height (g- n), implying a closer relationship between the glabella and nasion in this patient. The anterior superior orbital widths of the frontal bone (sorl-sorr) and the superior lateral orbital widths

(slorl-slorr) were increased.

Discussion: The predominant measured deformity of the frontal bone was along the region of the supra-orbital ridge at its junction with the nasal bones and the zygomatic bones. In the region of the ethmoid and sphenoid bones, the distances were normal or if anything, were reduced. These measurements reflect the clinical picture which shows some prominence of the supra-orbital ridge but a mild degree of proptosis.

Page jl6 Crouzon Syndrome t=1 tJrttttrN À t, N) Ê O OQ b'o b'o b'o b- b!a b'o!. i b3 bö98 o o o o o o o o o o o oã æã n-snml '(, FÚ snml-morl ¿È morl-sorl Ê¡¡.) sorl-slorl ôiJ slorl-2fl l- zfl-zfsl zfsl-slorl (ì n-snru oãfrô snmf-moÍ 5G I ¡J U' morr-sofr I sorr-slorr I F A¡O Fl r.rl slorr-zfr tÞ zft-zfsr zfsr-slorr 1O I I Êv n-fc I )ò. I ì+ Ât fc-cpal I õÞ tì cpal-cppl t- o\o cppl-ofaml v2 lrl 4 morl-ofaml oË Ð fc-cpar o 4È cpar-cPpf È cppr-ofamr morr-ofamr HO XáLlx ofaml-sobfl €=. sobfl-zfsl t¡r t- .oU) .D ¡J spal-cppl ãÞ o =. u, ofamr-sobf¡ I ;'' F sobfr-zfsr !r i+ ô spar-cPpr 'ô s I (t) I Fr fll ß g-n Þã' s-g U =l0 sorl-spal À¡ .+ sorr-spar o ãÞ sor[-sorr Ø slorl-slorr o Oa(\ spal-spar Ø \ (D 3.4.18.5 The Zygomatic Bone of Patient AY

Distances (Figure 3.32(9)): Similar pattern profiles were recorded bilateralty. The fronto-

zygomatic suture distance was increased bilaterally (slorl-2fl, slorr-zfr). The zygomatico-

temporal suture distance (ztr-pan) was increased on the right. The length of the lateral orbital

rim (orr-ilorr) was decreased on the right.

Dimensions (Figure 3.32(9)): The dimensions were not significantly different from the

experimental s tandard.

Discussion: The length of the fronto-zygomatic suture was increased. The abnormality was not

as severe as in the patieqt of a similar age (Patient LW). The suture deformity did not have a

significant impact on the measured dimensions of the zygomatic bone.

Figure 3.32(Ð Z Scores of the Distances and Dimensions of the Zygomatic Bone for Patient AY compared with the 6 Year Old Experimental Standard

Distances 6.00 Dimensions R 5.00 L

4.00

3.00

2.00

1.00

0.00 -1.00

-2.00

-3.00 5==€EEEEEEE=E È¡¡hÈãEÈEtiE!E EË5ãb5É-ÈÈ! .9èoÐ?+N=1?-lÀñ-l Êã.ã"3i\ff;ÌËF: \¡ ñ-l J.lE ËççRåEÉEË*=EF 5Ë**ëtEËË*:äs E Ë r rãå

Page 318 Crouzon Syndrome 3.4.18.6 The Vomerine Bone of Patient AY

Distances. Dimensions and Angles: (Figure 3.32(h)): The distances measured were not significantly different from the experimental standard. The longitudinal dimension was not significantly different from the experimental standard. The angle of the vomer relative to the cranial base (s-n/h-ans) was significantly decreased.

Discussion: The vomer showed some variation in this patient but remained close to normal limits. The decreased angle of the vomer may partly result from the cranial base deformity in this patient, where the cranial base angle was found to be reduced (see craniofacial dimensions and angles).

Figure 3.32(h) Z Scores of the Measurements of the Vomer for Patient AY compared with the 6 Year Old Experimental Standard

Z score Distances Dimension & Angle 3.00 2.00

1.00

0.00

-1.00

-2.00

-3.00 Ø cd (d I I

Chapter 3 Page 319 3.4.18.7 The Ethmoid of Patient AY

Lateral Ethmoid Plate (Figure 3.32(i)):

Distances: The lateral ethmoid plate distances, forming the medial orbital wall, were reduced in height anteriorly (nlil-morl, nlir-mon) and posteriorly (ofaml-msl, ofamr-msr), but not in length. The junction of the lateral plate with the cribriform plate (frontal ethmoid attachment) was not significantly different from the experimental standard.

Cribriform Plate (Figure 3.32Q\:

Distances: The spheno-ethmoid synchondrosis on the left (es-cppl) was increased in length with a tendency for an increase on the right. The anterior widths of the cribriform plate were in the experimental range. The length of the cribriform plate was normal.

Angles: The cribriform plate was not depressed.

Medial Ethmoid Plate (Figure 3.32Q):

Distances. Dimensions and Angles: The medial ethmoid plate measurements were within the normal limits of the experimental standard.

Discussion: The lateral ethmoid plate was reduced in height reducing orbital volume and contributing to the proptosis. The cribriform plate shows an increase in width posteriorly while the medial plate was normal. The spheno-ethmoid synchondrosis appears to di¡ect the anterior growth laterally contributing to the increased inter-orbital distance. The splay of the lateral plates were decreased as a result of the posterior broadening. The pathology of the ethmoid bone was not as severe as the other patients and the resultant clinical deformity was less profound.

Page 320 Crouzon Syndrome Figure 3.32(i) Z Scores of the Measurements of the Lateral Ethmoid Plate for Patient AY compared with the 6 Year Old Experimental Standard

Z score Distances Dimensions & Angles 4,00 Medial orbital Frontal ethmoid attachment 3.00 -_-__L- L. -R

2.00

1.00

0.00

-1.00

-2.00

-3.00

-4.00

-5.00 ôÊc4 Ê.8 8.H c=otr=é rOã= EË ËË ,lE ;;5€ E E E:.e ãFðH Eãb"9.F ðo EE LO9E Hã-'-ã Éo ËÈ> trd9É =Q E

Figure 3.32(l) Z Scores of the Measurements of the Cribriform and Medial Ethmoid Plates for Patient AY compared with the 6 Year Old Experimental Standard

Zscore Cribriform plate Medial plate 5.00 Angles Distances Dimensions 4.00 _L_

3.00

2.OO

1.00

0.00

-1.00

-2.00 kkL L .r èo Éo.o. NO.O. Þ.itù 'Þ (.) *aÞ. t+ o. o. s 8 3 î€ ? I v(J() v(Jo eoúú>J d"ã ? õ å () É €Éå i i-sL --- *E s o. fit(d (.) qgÈ Êd ØØll

Chapter 3 Page 321 3.4.18.8 The Sphenoid of Patient AY

Lesser Wing (Figure 3.32(k)):

Distances: The length of the lesser wing was increased on the left medially (ofaml-acl) and decreased posteriorly (acl-spal) implying lateral prominence of the anterior clinoid process.

Dimensions and Angles: The dimensions and angles were not significantþ different from the experimental standard.

Pterygoid Plate (Figure 3.32(k)):

Distances and Angles: The medial pterygoid plate height (ptsl-hpl) on the left was significantly increased. The remaining pterygoid plate distances and axes were not significantly different from the experimental standard.

Greater Wing (Figure 3.32(L)):

Distances: The measured lateral and orbital distances were not significantly different from the experimental standard. Landmarks on the squamous sphenoid bone (spt and spc) could not be identified bilaterally, due to fusion of the calvarial bone in this region and hence all the distances of the lateral part of the bone could not be measured. The posterior part of the greater wing was increased at the spheno-petrous temporal suture (inferior) (fosr-ptsr) on the right side, and at the posterior floor of the middle cranial fossa (fosl-petal) adjacent the superior spheno-temporal suture (superior) on the left side.

Dimensions and Angles: The angle of the floor of the greater wing (zfsl-gwml-ptsl, zfsr-gwmr- ptsr) was decreased. The angles of protrusion of the greater wing were increased (zfsl-gwml

/gwmr-zfsr and gwll-gwmVgwmr-gwlr) indicating the broader position of the wings.

Landmarks on the squamous sphenoid bone (spt and spc) could not be identified bilaterally, due to fusion of the calvarial bone in this region and hence the distances of the lateral part of the bone could not be measured. The posterior angle of the greater wing (fosl-petallpetar-fosr) was normal.

Page 322 Crouzon Syrulrome Figure 3.32(k) Z Scores of the Measurements of the Lesser Wing and Pterygoid Plate of the Sphenoid for Patient AY compared with the 6 Year Old Experimental Standard

Z score Lesser Wing Pterygoid plate 3.00 Distances Dimensions & Angles , R L Dista¡ces R Angles 2.00

1.00

0.00

-1.00

-2.00

-3.00 ÈKHÈ 9ÉO ÈÉËo Þ.É=o Èo EE.q dor E,tor.o .tr.coo Er -l?ã É'i'd -L cEo 14ÈÉ= 9â |:oØ i1 Erä EE* Ê

Figure 3.32(l) Z Scores of the Measurements of the Greater Wing of the Sphenoid for Patient AY compared with the 6 Year Old Experimental Standard

Zscore Lateral Orbital Posterior Dimensions & Angles 8.00 -ñ--- L R L R L

6.00

4.00

2.00 --...\

0.00

-2.00

-4.00 EEE, E:E ES i4S OU oo € -+ -*F F q ii ã?ê 'õ'd -r -ô?Ëúíúã t"íÉ € ; : >b>: 6 üñ €li E59 60 60 FìõH' Ð¿ú {a -l ¿ å ÈÐ= -o ,9.990q¡Ì iv Ð3

Chapter 3 Page 323 3.4.18.8 The Sphenoid of Patient AY (continued)

Bod)' of Sphenoid (Figure 3.32(m)):

Distances: The left inferior lateral distance (gwml-ptsl) was increased along with the lateral

height of the spheno-occipital synchondrosis bilaterally (ptsl-petal, ptsr-petar). The anterior body was increased in width at the spheno-ethmoid synchondrosis (es-cppl, es-cppr). The optic foramen was closer to the cribriform plate at the posterior frontal ethmoid atüachment (cppl- ofpml, cppr-ofpmr) with a corresponding increase in the left lateral sella length (ofpml-petal) with a similar trend on the right. The distances of the floor were not significantly different from the experimental standard except the increased left posterior width (ptst-h).

Dimensions and Angles:,The dimensions revealed a normal distance between the greater wing medial points at the anterior inferior body width (gwml-gwmr). The distance between the anterior optic foramina (ofaml-ofamr) was increased. The inferior spheno-occipital synchondrosis (ptsl-ptsr) was increased while the superior spheno-occipital synchondrosis

(petal-petar) was normal. The height of the posterior sphenoid was increased on the left (ptsl- pcl). The angles of the lateral protrusion of the body from the midline were increased superiorly

(s-n/ofpml-peta1, s-n/ofpmr-petar).

Discussion: This lesser wings of the sphenoid bone were relatively normal in this patient. The left anterior clinoid process was laterally displaced. The pterygoid plates were not greatly different from the experimental standard. The size of the greater wings was normal however the angle between the greater wings was increased due to less anterior protrusion of the greater wings with a greater degree of lateral splay. The spheno-temporal sutures were incrsased in length and pathology at this site influence the anterior or posterior position of the greater wing.

The spheno-ethmoid synchondrosis was elongated, and the spheno-occipital synchondrosis was increased in height. The dimensions around the sella were increased implying the sella was enlarged and would be consistent endocranial resorption in this area.

Page 324 Crouzon Syndrome Figure 3.32(m) Z Scores of the Measurements of the Body of the Sphenoid for Patient AY compared with the 6 Year Old Experimental Standard

Zscore LateraVposterior Anterior Sella Base/floor Dimensions Angles 5.00 L R LRLR 4.00 3.00 2.00

1.00 0.00 A -1.00 -2.00 -3.00 -4.00

Ødo Ê.É ç Éd cd -Øøda === do :1 -À EE.E H. +ei ç-o q-dèo ä6 ìi ¿9?o ;oÞ-o O' å ;+ Å ++ E OJÊ o¿Þ ?¿ ä:Éå åå€ Ëåäå 514o otr ÈE À! Èç *E o&**ç ãäå eoÀÈ Èäi O,F F 8E Oç aE öË E 'ååEåc-\o: o òoE ¿ ãìÈ ø¿1

Chapter 3 Page 325 3.4.18.9 The Temporal Bone of patient Ay

Distances (Figure 3.32(n)):

Squamous Temporal Bone: The squamous temporal bone was not fully measurable in this child due to lack of visibility of the asterion (as) and sphenion (spt). The remaining distance, the medial mastoid height (mal-smfl) was not significantly different from the experimental standard on the right but increased on the left.

Extemal Auditory Meatus: The left posterior superior rim of the external auditory meatus

(eampl-pol) and the superior anterior rim (pol-eamal, por-eamar) bilaterally were increased. The laterar mastoid prominence (mar-eamir) was increased on the right.

Z.r¿gomatic Process: The zygomatic process showed some similarity in the pattern profiles between the left and right sides, but was generally within the normal range. The left zygomatico-temporal suture (parl-ztt) was increased.

Petrous Temporal Bone (Figure 3.32(o)): The sphenoid-petrous temporal suture (superior)

(fisl-petal) was increased in length on the left with a tendency to be increased on the right. The occipital mastoid (inferior) suture (mal-jflI, mar-jflr) was increased in length. The petrous temporal-occipital suture (petal-jfpl, petar-jfpr) was increased bilaterally. The jugular foramen width (jfll-jfml, jflr-jfmr) was nanowed. The mastoid to jugular foramen distance was increased bilaterally, along with the left medial temporo-occipital suture (inferior) (fml-ptsl).

The spheno-petrous temporal suture (ptsr-fosr) was increased on the right.

Dimensions (Figure 3.32(o)): The petrous ridge distance (petal-petpl, petar-petpr) was increased bilaterally and the distance between the external auditory meati (pol-por). The angle of the zygoma projection (petal-au1-ztl, petar-aur-ztr) and the angles of the auditory canal (pol-iaml

/iamr-por) and the petrous temporal bone (petpl-petaVpetar-petpr) were normal.

Discussion: The predominant abnormalities were in the region of the external auditory meatus which was distorted with increased distances. The zygomatic process was essentially normal.

Lengthening of medial and lateral temporal occipital sutures resulted in narrowing of the jugular foramen. The external auditory canals were displaced laterally however the angles of splay of the bones were not significantly different from the experimental standard.

Page 326 Crouzon Syndrome Figure 3.32(n) Z Scores of the Distances of the Temporal Bone for Patient AY compared with the 6 Year OId Experimental Standard

Z score Squamous External Auditory Meatus Zygomatic Process 5 L R L R L R 4

J ^

2 L I

-l

!Ødç kk9L !P!Lk LL *d-C !ødq .=Þod'= çoL!á äT E b tr oÉ tr EtrAÉtr=Èo6= ç -lãtq1'ò E f 3, Ë.f i F 3.3. ç d= ) 3- E õ dçi:e oq b.úÉ åB E3åsq E d 9 Ë' 6 N € q ¡äãË ä* E+ ã ã É 9Ë ÞtroÀtr ã rE ! o dd E E3 E.E o oo oodd

Figure 3.32(o) Z Scores of the Measurements of the Temporal Bone for Patient AY compared with the 6 Year Old Experimental Standard

Z score Petrous Dimensions Angles 5.00 L R L R

4.00

3.00

2.00

1.00

0.00

-1.00

-2.00

g s U g-oEeeF 3ÞãEo.400 o.iF s'ã ÉE E XSNN ÀJJÀ +'$i È P Ëå"-'- 9q.9ì"¡F ì-o.¿J.qÈJa g,e.È e k.rdd È Ed E ËÈå¡ dd¿¿ E'&ÊË *Èd äËËEëE g aq. > d J. d=Eg8-8- E.? È

Chapter 3 Page 327 3.4.18.10 The Parietal Bone of Patient Ay

Distances: The key landmarks for the parietal bone for Patient AY were not visible due to suture fusion and could not be reliably estimated. Therefore the parietal bone was not measured and a pattem profile of Z scores was not generated. The measurement data for the experimental standard are reported in Appendix2.

3.4.18.11 The Occipital Bone of Patient AY

Distances (Figure 3.32(p)): The jugular foramen showed a trend for reduced distances with one distance (fll-jfpl) significantly reduced. The left medial temporo-occipital suture (inferior)

(frnl-ptsl) was increased- in length with a tendency to be increased on the right. The inferior spheno-occipital synchondrosis (ptsl-ptsr) was increased in length (see sphenoid and cranial base sutures for other distances). The foramen magnum was not significantly different from the experimental standard.

Dimensions (Figure 3.32(p)): The dimensions were not significantly different from the experimental standarci.

Discussion: The occipital bone showed some distortion along the sutures with the temporal bone, with narrowing of the jugular foramen.

Figure 3.32(p) Z Scores of the l)istances and l)imensions of the Occipital Bone for Patient AY compared with the 6 Year Old Experimental Standard

Zscore Dimensions 3.00 _ _ ?5j1n*r --- * L R 2.OO

1.00

0.00

-1.00

-2.00

-3.00

-4..00 k ÀÊr =o¡o I 9ô- oo O{ qÉçÈ cg Ê I Ð I îo 3Ë+.1 k -t¿ I Ë. -ä.8 sÈ_8t Èo. Or E orÈoo

Page328 CrouzonSyndrome 3.4.18.L2 The Cranial Base Sutures of Patient AY

Anterior Cranial Fossa (Figure 3.32(q)): The spheno-ethmoid synchondrosis (es-cppl, es-cppr) was increased in length. The spheno-frontal suture (cppl-spal, cppr-spar) in the anterior cranial fossa was reduced in size. In the orbit, the spheno-frontal (spal-zfsl, spar-zfsr) and spheno- zygomatic (zfsl-gwll, zfsr-gwlr) sutures were normal.

Middle Cranial Fossa (Figure 3.32(q)): The spheno-petrous temporal sutures were increased in length superiorly (fisl-petal) on the left and inferiorly (fosr-ptsr) on the right.

Posterior Cranial Fossa (Figure 3.32(q)): The superior (petal-jfml, petar-jfrrn) and left inferior

(fml-ptsl) medial temporo-occipital sutures were increased in length. The right occipital mastoid suture (jflr-petpr) was increased in length. The superior spheno-occipital synchondrosis (petal-petar) was normal, while inferiorþ (ptsl-ptsr) and laterally (ptsl-petal, ptsr-petar) the lengths were increased.

Discussion: Significant suture abnormality was found in the cranial base anteriorly with no lateral involvement. Presumably the sutures at this site are less severely involved in the pathological process. Posteriorly, the temporal bone was involved laterally, while medially the spheno-occipital synchondrosis was deformed.

Figure 3.32(q) Z Scores of the Dimensions of the Cranial Base Sutures for Patient AY compared with the 6 Year Old Experimental Standard

Z scote Anterior Cranial Fossa Middle Cranial Fossa Posterior Cranial Fossa 5.00

4.00

3.00 2.00

1.00 0.00 -1.00

-2.00 -3.00 !-L-L ØØddØØ L-k-ÞÞLÈÞ õ. äã H -2.ä F -! LU!CCØØO.Ò-cdØ(cd FFâÊ.\iã"ã. 'ii +.r o o.) o- o, '?'Ìl-!¿Ê.Õ.o.,o.o.qiq!Q.O6-¡ÒOO-O1¡ iÈo.o.r..r ËHtrË-T¿+ZJ¿ oTEFEFR* E E +, tZ (ÊZ ÒO bO l.= t= ç, Ê_"&ËË,ÊËo8,Ëaa

Chapter 3 Page 329 3.4.18.13 The craniofacial Dimensions and Angles of patient ay

Dimensions and Angles (Figure 3.32(r)): The patient's mouth was open during the CT scan

making the measurements of the facial height and SNB angle (s-n-sm) invalid. The SNA (s-n-

ss) angle was reduced. The cranial base angle (ba-s-n) showed a tendency to be more acute in this patient. The cranial base dimensions were not significantly different from the experimental standard.

Discussion: The maxilla was retruded with the cranial base angle borderline reduced in this patient.

Figure 3.32(r) Z Scores of the Craniofacial Dimensions and Angles for patient aY compared with the 6 Year old Experimental standard

Zscore Facial heights Facial Angles Cranial Base 4.00 SNA SNB Angle Dimensions 3.00

2.00

1.00

0.00 -l.00 -2.O0 À -3.00

-4.00

q ç6d I I q frEä É I cl.kl É¿¿' I É CÚ -o ,o I ,.o

Page 330 Crouzon Syndrome 3.4.L9 Clinical and Radiographic Findings for Patient HC

Clinical Features

This patient was frst seen at the ACFU at the age of 12yearc and was reviewed again at the age of 15 years (Figure 3.7). No family history was available due to his orphan status. At the age of 10 he had undergone a fronto-orbital advance elsewhere. The details of the indications and the surgery performed were not available. On review at age 15 years his head shape was brachycephalic with proptosis and mild hypertelorism. A divergent squint and evidence of exposure keratitis were present. He had a moderate degree of conductive deafness with bilateral absent external auditory meati and atresia of the canals. The maxilla was hypoplastic, with a

Class III occiusion and hyponasal speech.

Lateral, Antero-Posterior and Basal Radiographs

Lateral, antero-posterior (AP) and basal radiographs had been performed. The lateral radiograph revealed the bony defect in the region of the coronal sutures as a result of the previous surgery. No cranial sutures were seen on the radiographs. The anterior cranial fossa was steep due to the swept up lesser wings of the sphenoid. The sella was large, with a prominent sphenoid sinus and the appearance of fusion of the spheno-occipital synchondrosis.

The temporal bone did not show the extemal auditory meati. A cervical spine fusion of C2-C3 andcalcif,rcationof the stylohyoid ligament were visible. The occlusion was class III. The AP view revealed the lesser wing swept upwards and prominence of the ethmoid sinuses.

Interosseous wires could be seen above the supra-orbital ridges bilaterally. There was a very mild copper-beaten appearance to the calvaria. The nasal septum was deviated to the right.

3D CT Reconstruction

Calvarial bones: Evidence of previous surgery was again noted by the absence of bone along the coronal sutures, and the evidence of wires above the supra-orbital ridge. No calvarial sutures were seen. The external auditory meati were absent.

Cranial base: The anterior cranial fossa revealed that the cribriform plate and the jugum sphenoidale bones were pushed down and thinned. The right side of the cranial base appeared

Chapter 3 Page 33Ì narower than the left side, although this may have resulted from the angle of the CT scan. The

sella was slightly large and the clivus was steep. The spheno-occipital synchondrosis was not patent. The foramen magnum had a pointed posterior margin.

Orbital: The appearance of the orbital aperture was of a vertical elongation. The medial orbiøl wall, the lacrimal area and the floor of the orbit demonstrated small bony defects. These were small errors of exclusion seen on the 3D CT bone reconstruction.

Maxilla: The right lateral upper incisor was missing. The anterior maxillary wall also contained an error of exclusion.

3.4.20 Features of the CT Scan and 3D Reconstruction for Patient HC that made Landmark Identification diffïcult

The calvarial landmarks (1, as, br, spt, spc) could not be identified nor reliably estimated. The peri-orbital sutures and cranial base landmarks were identified from the regional bony contours and junctions defined in the landmarks (Figures 3.15-3.26). Landmarks for the peri-orbital structures were difficult to identify on the 3D CT reconstructions and the 2D axial slices were relied on.

Page 332 Crouzon Syndrome 3.4.2t Results and Discussion of the Quantitative Analysis of Patient IfC compared with the Adult Experimental Standard

Figures 3.33(a)-(r)

Chapter j Page 333 3.4.2L.1 The Mandible of Patient HC

Distances (Figure 3.33(a)): The majority of distances were not significantly different from the experimental standard. The left anterior superior body distance (id-emlil) was increased, and the left posterior ramal length (cdl-gol) was reduced.

Dimensions and Angles (Figure 3.33(b)): This patient had the largest number of abnormal dimensions and angles of all the patients. The intercondylar distance (cdl-cdr) and intercoronoid base distance (cbl-cbr) were decreased. The anterior symphyseal height (gn-id) was increased. The gonial angles (cdl-gol-gn, cdr-gor-gn) were increased bilaterally along with the coronoid base (ctl-cbl-id, ctr-cbr-id) and coronoid dental angles (ctl-cbl-em1il, ctr-cbr-emlir).

Discussion: The increased anterior symphyseal height was possibly a secondary compensatory change related to the class III occlusion. Deformity at the angle was most pronounced in this patient suggesting a possible primary mandibular deformity. The decreased intercondylar distances suggested a cranial base effect.

Page334 CrouzonSyndrome rã I I I N J- b) (r { u) N) o N) Ø ¡L) ,,! - - te b ir O b Õ ãaci¡àa¡=aca8 =;;ì O O 0a Õ Õ o o o o o o o o= ã oã (D ã G gol-gor 3 .(, id-emlil (, I .Y(, cdl-cdr åor (,te oct emlil-cbl cbl-cbr Â¡ =tv tì i/ em l il-eml ir id-cbl ôu)EN 5Lì cbl-ctl Pv) cdl-ctl o ðo (ÞX Ø Ëo t- gol-cbl I Hq) ctl-mnl {E Ø Þ cdr-ctr 6i Frr gor-cbr ÈF¡ mnl-cdl {o oo cdl-gol gn-id =\J gol-gn =v) gn-cdl iD ;¡ ¡+= (t) - ¡rl t') gn-cdr Px. xiÅ a ct) F!oo ¡l l!5 id-emlir 5(+ cdl-mnl-ctl XÈ emli¡-cbr f+> cdr-mnr-ct¡ c> LÈ loa !¡ cdl-gol-gn id-cbr U)E oo f.àÈ cdr-gor-gn 5u) I cbr-ctr ctl-cbl-id I (hÉ fo I ùc ctr-cbr-id o F Èo' c) Ø ÈrD ctr-mnr ã € ctl-cbl-emlil Èz ß Põ' mnr-cdr Þ ì ctr-cbr-em1ir ctÞ È (Þ gol-gn-id cdr-gor gor-gn-id (D ^9 0a gor-gn o (\ gol-gn-gor Fl (4 3.4.21.2 The Maxitla of patient HC

Distances (Figure 3.33(c)): The left anterior border of the lateral ethmoid plate (nlil-morl)was decreased compared with the experimental standard. The posterior lateral orbital floor (msr- iobfr) was increased on the right. The anterior lateral orbital floor (iobfl-orl, iobfr-orr) was decreased on both sides. The left maxillary orbital rim (orl-nlil) was increased in length. The anterior alveolar margin (emlsl-pr, emlsr-pr) was decreased in length. The right upper pyriform margin distance (alr-inmr) was increased. The anterior alveolar height was increased (pr-ans)' The right posterior alveolar margin (emlsr-mxtr) was reduced in length and the

posterior palatal height (em1sl-gpfl, em1sr-gpfr) was reduced bilaterally.

Dimensions and Angles (Figure 3.33(d)): The dimensions of the lateral height (morr-emlsr) and posterior height (gpfr-msr) on the right side were increased. The width of the nasal aperture was.reduced (all-alr). The superior/occlusal angle (snml-msVemlsl-pr) and the palatayocclusal (ans-pns/emlsl-pr) angle on the left were increased. The maxillary arch angle (gpfl-pr-gpfr) was increased.

Discussion: The maxilla of Patient HC was not small. Most significant measurements showed an increase in the posterior distances. The anterior measurements particularly around the orbit, and the teeth were reduced. The pattern of deformity of the maxilla in patient HC was of a broad orbital region with increased height to the maxilla posteriorly and laterally (right side). The anterior alveolar height was increased. The maxilla confirms the impression of a broad

maxilla with increased height and lacking corresponding anterior projection.

Page 336 Crouzon Syndrome Figure 3.33(c) Z Scores of the Distances of the Maxilla for Patient HC compared with the Adult Experimental Standard

Zscore Orbital Anterior Lateral Palatal 6.00 L R L R L R LR 4.00

2.00 ---o

0.00 o -2.00

-4.00

-6.00

-8.00 ¿i H,¡.! o o ¡! çÊ = iE.ilEE ñ goT À É É i oo = i Ê Êìoo i Êû ø.4 ú ET.9Ñ E i.9 ÍÌiiîE =c ùH C I F1 O dã? ' o -rel¡ r å+ bc! c E E ?E ÈËÉãF" F¿Éco tro i = = -Ê EÐ

Figure 3.33(d) Z Scores of the Dimensions and Angles of the Maxilla for Patient HC compared with the Adult Experimental Standard

Z score Dimensions Angles 4.00

3.00

2.00

1.00

0.00

-1.00

-2.O0

-3.00 qèooo ¡¡oocc ,=Ø ÈÈ iEiEÉEEËþË!ç!õõG,¡-LJ +È99 ¿: iJõ.õ.4øç3?oÉ'- 9tsÈEE ,Í¿ ãbÚqebñoÑ ctròd boooo qa -!¿ø{ oú cc EE i7=ûFIïP+ *ccdñ

Chapter 3 Page 337 3.4.21.3 The Nasal Bones of Patient HC

Distances. Dimensions and Angles (Figure 3.33(e)): The nasal length (na-n) was increased compared with the experimental standard. The other distances and dimensions in this region were not significantly different from the experimental standard. The only significant angle was the nasaVanterior cranial base angle (s-n-na) which was reduced.

Discussion: The measurements of the nasal bones confirmed the trend of the pathology in this region. The increased length of the midline nasal bone and the reduced nasaVcranial base angle were consistent with the maxillary deformity of increased height and lack of anterior projection.

Page 338 Crouzon Syndrome Figure 3.33(e) Z Scores of the Measurements of the Nasal Bones for Patient HC compared with the Adult Experimental Standard

Zscore Distances Dimensions Angles 3.00 L R o 2.OO

1.00

0.00

-1.00

-2.00

-3.00 É h d E E tr Êts d c E ò1 6 d -lb E E trts É ëÉ É E

Chapter 3 Page 339 3.4.21.4 The Frontal Bone of Patient HC

Distances (Figure 3.33(f)) :

Supra-orbital Region: The majorify of the supra-orbital distances were not significantly different from the experimental standard. The supero-medial length of the orbital rim (morr-sorr) was increased on the right with a similar trend seen on the left side. The left lateral fronto-zygomatic suture (2fl-zfsl) was reduced.

Ethmoid Attachment The nasal root projection (n-fc) was significantly reduced while the lateral length of the ethmoid plate at the frontal ethmoid attachment (cpal-cppl, cpar-cppr) was significantly increased in length. The width of the attachment at the ethmoid posteriorly (cppl- ofaml, cppr-ofamr) was reduced as was the orbital frontal ethmoid attachment (morl-ofaml, morr-ofamr).

Sphenoid Attachment: The attachment to the sphenoid bone had distances which were not significantly different from the experimental standard. The parietal attachment (spc-br) and sphenoid attachments (zfs-spc and spc-spa) were not recordable due to the fusion of sutures and hence poor visibility of landmarks in this region.

Dimensions (Figure 3.33(f)): The depth of the anterior cranial fossa (spal-sorl, spar-sorr) was decreased bilaterally. The anterior superior orbital width was increased (sorl-sorr) as was the posterior width between the tips of the lesser wings (spal-spar).

Discussion: This patient had a fronto-orbital advance performed some 5 years previously leading to some distortion of the primary pathology in this region. Despite this, many of the ethmoid and sphenoid distances should be minimally affected by this surgery. The measurements still reveal a broadening of the frontal bone, both anteriorly and posteriorly, with a reduced depth of the anterior cranial fossa, and suggest the deformity is again present.

Medially, however, the projection of the frontal bone was not significantly different from the experimental standard. The overall prominence of the frontal region was normal as measured from the sella to the gnathion. There was an increased length of the frontal ethmoid attachment cranially with reduced width at the orbital level. The narrow frontal ethmoid attachment correlated with a normal interorbital distance (see ethmoid bone).

Page 340 Crouzon Syndrome fn summary, the assessment in this region was complicated by the previous surgery. The measurements confrm the features of a broad frontal bone with a shallow anterior cranial fossa and a shape disturbance in the region of the ethmoid.

Figure 3.33(Ð Z Scores of the Distances and Dimensions of the Frontal Bone for Patient HC compared with the Adutt Experimental Standard

Z score Ethmoid Sphenoid Dimensions 6.00 L R L R LR 4.00

2.00

0.00 oAo -2.O0 o -4.00

-6.00

-8.00

- 10.00 ËÈLLLÉç tr o o o N( o çé L ! Lç.- ù õ ÈÉ É d oc c E o o o Nç: o :,Í'oN:ï F Í.i"8åãå tl_ rã+| !- l7 | t E ?z ¿ I z ' Y Y!! ç! F ä - ÅËEË;È¿ d ! HE=ã ¿*i_? ùdJ-¿ =¡ o. !-ô ñ "EÞE;iEçÈØ N N oo! tro tsôÀ ä9v,3* ÉtrØ 3*bõÉ ,8.- oÈ o o

Chapter j Page 341 3.4.2L.5 T}l.e Zygomatic Bone of Patient HC

Distances (Figure 3.33(9)): Several measurements were outside the experimental standard

range. The zygo-maxillary suture (orl-iobfl, orr-iobfr) was signifîcantly reduced bilaterally. The

anterior height of the inferior orbital fissure (iobfr-gwlr) was increased on the right. The

spheno-zygomatic suture (gwll-zfsl, gwlr-zfsr) was increased in length bilaterally. The height

of the frontal process was decreased (zfr-ztr) on the right side. The inferior length of the

zygomatic arch (parl-zmil, parr-zmir) was reduced bilaterally.

Dimensions (Figure 3.33(g)): The dimensions showed some variance from normal limits. The length of the zygomatic bone (parl-orl) was reduced on the left with a similar trend on the right.

The lateral depth of the zygomatic bone (gwll-ilorl, gwlr-ilorr) was also reduced bilaterally.

Discussion: Lengthening and presumed fusion of the spheno-zygomatic suture produced a pattern of deformity where there was a reduction in the anterior-posterior dimension of the zygomatic bone. Fusion of the zygo-maxillary suture would limit anterior growth of the maxilla and promote increased height.

Figure 3.33(9) Z Scores of the Distances and Dimensions of the Zygomatic Bone for Patient HC compared with the Adult Experimental Standard

Distances t 1.00 Dimensions 9.00 L R 7.00 5.00 3.00 1.00 -r.00 -3.00 -5.00

-7.00 -9.00 È+¡8q:;tsEEÈ!:i E==EEEEEEFEEE.9ÐÐ?iN='T?¿?FÉ Ë r, ã€ i i,? : € i Ë F 3 ÈgR*;FÉEÉ**EF ËË*ç;'ËEËËfËgÊ

Page 342 Crouzon Syndrome 3.4.21.6 The Vomerine Bone of Patient HC

Distances. Dimensions and Angles (Figure 3.33(h)): Most distances were not significantly different from the experimental standard except the ethmoid-vomerine junction (vei-ves) which was reduced in length. The vomerine length (h-ans) was also reduced. The angle of the vomer relative to the cranial base (s-nlh-ans) was significantly increased. This may have resulted from the cranial base deformity.

Discussion: In this patient the vomer showed a tendency to be smaller and angled further inferior from the cranial base. This reflected a lack of forward growth in preference for downward growth which may then have directed the position of the maxilla.

Figure 3.33(h) Z Scores of the Measurements of the Vomer for Patient HC compared with the Adult Experimental Standard

Z score Distances Dimension & Angle 3.00 2.00 l.00 0.00

- 1.00

-2.00

-3.00 Ø I I o o. aú I I I I I À 0) o) Cd I

Chaprer 3 Page 343 3.4.2L.7 The Ethmoid Bone of Patient HC

Lateral Ethmoid Plate (Figure 3.33(i)):

Distances: The lateral ethmoid plate distances, forming the medial orbital wall, were reduced in height and in length. The anterior border of the lateral plate (nlil-morl) was reduced on the left and the posterior border of the lateral plate (ofamr-msr) was reduced on the right. The orbital border of the frontal ethmoid attachment (ofaml-morl, ofamr-morr) was significantly reduced bilaterally. Additionally, the anterior (morl-cpal, morr-cpar) and posterior (cppl-ofaml, cppr- ofamr) frontal ethmoid attachment were reduced in width bilaterally (see frontal bone).

Dimensions and Angles: The inter-orbital dimension (morl-mon) and the posterior superior width between the optif canals (ofaml-ofamr) were not significantly different from the experimental standard however the dimensions between the anterior and posterior inferior lateral plate (nlil-nlir and msl-msr) were reduced. The splay of the lateral plate was decreased posteriorly and anteriorly (nlil-morVmorr-nlir, msl-ofamVofamr-msr).

Page 344 Crouzon Syndrome Figure 3.33(i) Z Scores of the Measurements of the Lateral Ethmoid Plate for Patient HC compared with the Adult Experimental Standard

Z score Distances Dimensions & Angles 2.00 Medial orbital wall Frontal ethmoid attachment LR LR 0.00

-2.00 \ -4.00

-6.00

-8.00

-10.00 !i4! h 2=!É=2 :ã8tr ?È À ïÌEelÌ FbtH E o E hf, o q bcÃ=Y: ÈË tO Éo = Éo a c.d\o oxì ËE =O c '¿, B

Chaprer 3 Page 345 3.4.21.7 The Ethmoid Bone of patient HC (continued)

Cribriform Plate (Figure 3.33O):

Distances: The length of the cribriform plate (cpal-cppl, cpar-cppr) was increased bilaterally.

The cribriform plate posterior width at the spheno-occipiøl synchondrosis (es-cppl, es-cppr)

was increased bilaterally. The right anterior cribriform plate width (fc-cpar) was reduced in length.

Angles: The lateral angle of the cribriform plate was increased on the right side (s-nicpar-cppr) but not on the left and was probably related to the reduced anterior width of the cribriform plate (fc-cpar).

Medial Ethmoid Plate (Figure 3.33O):

Distances: The medial plate had a reduced length at its articulation with the vomer (ves-vei) (see vomer) and in its nasal root projection (n-fc).

Dimensions: The dimensions were within the limits of the experimental standard

Discussion: The lateral plate was reduced in size and contributed to the reduced orbital size. 11re fronto-ethmoid junction was reduced in width and may be related to the decreased lateral plate size and orbital pathology. The decreased size in this region corresponded with a lack of hypertelorism and was adjacent to the previous surgical site. The cribriform plate shows an increase in width posteriorly and an increased length. This may be due to suture abnormality or bone resorption which gives the appearance of a larger cribriform plate region. The medial plate was normal or reduced in its dimensions. Anteriorly, the inter-orbital distance was normal. The findings of the ethmoid bone in this patient may be influenced by the previous surgery.

Distances and dimensions such as the inter-orbital distance, the anterior part of the lateral plate and the anterior region of the cribriform plate such as the foramen caecum may all be distorted. 'Without knowing the exact nature of the original regional pathology, and the precise placement of the surgical cuts in the fronto-orbital advance, and the distance advanced, it was difficult to interpret the anterior results rneaningfully. Regardless of this, the spheno-ethmoid synchondrosis was widened and the size and splay of the lateral plates were decreased, as the principal posterior pathology of the ethmoid bone had not been addressed surgically.

Page 346 Crouzon Syndrome Figure 3.33(i) Z Scores of the Measurements of the Cribriform and Medial Ethmoid Plates for Patient HC compared with the Adult Experimental Standard

Zscore Cribriform plate Medial plate 5.00 Distances Distances Dimensions 4.00 R 3.00 2.00 l 00 0.00 -1.00 -2.00 -3.00 -4.00 -5.00 kkk q) ,e cg ô- ô- Ë.b.€ I Èitit ryÇ I :fß EEEvoo ubo I I 0) ?99 e(J *È ii.s C) €E 8 'c ËHl 0) ol3 33É t¡

Chapter 3 Puge 347 3.4.21.8 The Sphenoid Bone of patient HC

Lesser Wing (Figure 3.33(k)):

Distances: The length of the lesser wing was increased posteriorly (acl-spal, acr-spar) and

anteriorly (spar-es) on the right side compared with the experimental standard.

Dimensions and Angles: The maximum width of the lesser wings (spal-spar) was increased

with an increase in the angle between the lesser wings (spal-es-spar). The other distances and

angles of the lesser wings were not significantly different from the experimental standard.

Pter)¡goid Plate (Figure 3.33(k)):

Distances and Angles: The length of the left lateral pterygoid plate (ptll-fool) was significantly reduced eompared with the experimental standard. The angles of the pterygoid axis were significantly increased (s-n/ptsl-hpl, s-n/ptsr-hpr) implying a lateral and posterior splay to the pterygoid plates.

Greater Wing (Figure 3.33(l)):

Distances: The measured lateral and orbital distances were not significantly different from the experimental standard with the exception of the spheno-zygomatic suture (gwll-zfsl, gwlr-zfsr) which was increased in length bilaterally (see also zygomatic bone). Landmarks on the squamous sphenoid bone (spt and spc) could not be identified bilaterally, due to fusion of the calvarial bone in this region and hence all the distances of the lateral part of the bone could not be measured. The posterior part of the greater wing was increased at the posterior floor of the middle cranial fossa (fosl-petal) on the left side.

Dimensions and Angles: The posterior sphenoid width (fosl-fosr) was reduced. While the angles of protrusion were increased (zfsl-gwmi/gwmr-zfsr, gwll-gwml/gwmr-gwlr), the angle of the floor of the greater wing was normal (zfsl-gwml-ptsl, zfsr-gwmr-ptsr). This would be accounted for by a narrowing of the body of the sphenoid bone posteriorly (see sphenoid body). The posterior angle of the greater wing showed a tendency to be reduced (fosl- petal/petar-fosr).

Page 348 Crouzon Syndrome Figure 3.33(k) Z Scores of the Measurements of the Lesser Wing and Pterygoid Plate of the Sphenoid for Patient HC compared with the Adult Experimental Standard

Z score Læsser Wing Pterygoid plate 8.00 Distances Dimensions & Angles Distances L R L R Angles 6.00

4.00

2.00

0.00

-2.00

-4.00 !lLL O d rl d EE.ç ^ - o. o. -ctt -É o- .o .É ,.8 o. .O tt + ?Ë E äÉ Øô-¡trL!ùr HçB ËÞ* e.r-cä9qÉ= ä-cEE o.o. t¡

Figure 3.33(l) Z Scores of the Measurements of the Greater Wing of the Sphenoid for Patient HC compared with the Adult Experimental Standard

Zscore Lateral Orbital Posterior Dimensions & Angles 12.00 L R L R L R 10.00

8.00

6.00

4.00

2.00

0.00

-2.00

-4.00 ?ç-ã 73 -ú1¿ o ÀÈÈtr,.11 ¿T ço ï' ,! 'd z-! o çÊúúd ,YN ùN ttro -" ã" E €E; .& ú6; 4û .ø.òúúÈi J t aÐ d NNã=ä 43

Chapter 3 Page 349 3.4.21.8 The Sphenoid Bone of Patient HC (continued)

Body of Sphenoid (Figure 3.33(m)):

Distances: The body dimensions were varied between and within regions. The lateral distances

were not significantly different from the experimental standard including the lateral height of the

spheno-occipital synchondrosis bilaterally (ptsl-petal, ptsr-petar). The anterior body showed

increased distances at the spheno-ethmoid synchondrosis (es-cppl, es-cppr), and reduced distances at the posterior frontal ethmoid attachment (cppl-ofaml, cppr-ofamr) and the anterior lateral body (cppl-ofpml, cppr-ofpmr). The right lateral sella length (ofpmr-petar) was increased. The distances of the floor were not significantly different from the experimental standard except the posterior widths which were reduced (ptsl-h, ptsr-h).

Dimensions and Angles: The dimensions revealed a normal anterior inferior body width (gwml- gwmr) and anterior superior body width (ofaml-ofamr). The inferior spheno-occipital synchondrosis (ptsl-ptsr) and the superior spheno-occipital synchondrosis (petal-petar) were reduced in length (the lateral spheno-occipital synchondrosis was normal) (see also cranial base sutures). The height of the body (acr-gwmr) was reduced on the right side. The angles of the lateral protrusion of the body from the midline were reduced superiorly on the right (s-n/ofpmr- petar).

Discussion: This sphenoid bone in this patient had slightly enlarged lesser wings with an increased angle of inferior protrusion. The spheno-ethmoid synchondrosis was elongated, and the sella was enlarged slightly. An increased angle of lateral protrusion of the greater wings was present with lengthening of the spheno-zygomatic sutures and some involvement of the spheno- temporal sutures. The spheno-occipital synchondrosis was reduced in width. This rnay have some bearing on the temporal bone development and the atresia of the auditory canal seen on the right in this patient (see temporal bone).

Page 350 Crouzon Syndronrc Figure 3.33(m) Z Scores of the Measurements of the Body of the Sphenoid for Patient HC compared with the Adult Experimental Standard

Zscore LateraVposterior Anterior Sella Base/floor Dimensions Angles 4.00 L R L RLR 3.00

2.OO 1.00 -o.öio - - 0.00 o -1.00 -2.00 -3.00 -4.00 -5.00

E*E ÞEE E -ØØdd E. E. Oó) + FE!:d > do n =o'o6 õ lÀ; -l ço qooo 9gU*å FåFãE-åEE y È .,^oil å97 Or o.i Fi" ¿ ¿ *+ B. iË ãi J -1. o¿ H bÈ¡¿ F¿iîËÈ-o=E *ÈÈ ¿ F EE É S¿å 5:3 0 qE dÉ È! XE h o t>tsÉ doÈtr ioÈa P,l+ = õH rbo 60 J+.È 3.8 so eoõ,È 5 H-8' c> o: @ã ¿ iq-ÈØ¿

Chapter 3 Page 351 3.4.21.9 The Temporal Bone of patient HC

Distances (Figure 3.33(n)):

Squamous Temporal Bone: The temporal squamous bone was not fully measurable in this child

due to lack of visibility of the asterion (as) and sphenion (spt). The remaining distance (ma-

smf) was not signif,rcantly different from the experimental standard.

External Auditory Meatus: The external auditory meatus was absent on the left. Only an

indistinct outline was visible in the region of the external auditory meatus on the temporal bone

and thus was not recorded. The right superior anterior rim (por-eamar) was decreased.

Zygomatic Process: The zygomatic process was generally within the normal range. The length

of the zygomatic arch (ztl-aul) was decreased on the left and the height of the articular fossa (afl-ael, afr-aer) was normal.

Petrous Temporal Bone (Figure 3.33(o)): The spheno-petrous temporal suture (superior) (fisr-

petar) was significantly decreased in length on the right. The jugular foramen width was not

significantly different from the experimental standard (flI-jfml, jflr-jfmr). lncreased distances

were recorded at the occipital mastoid suture (inferior) (mal-jfll) on the left, along with the left

medial temporo-occipital suture (inferior) Cfml-ptsl).

Dimensions (Figure 3.33(o)): The length of the petrous temporal ridge (petal-petp1, petar-petpr)

was normal bilaterally. The dimension between the internal auditory meati (iaml-iamr) and the

mastoidale points (mal-mar) was decreased. The angle of the zygoma projection (petal-aul-ztl,

petarau-ztr) and the angle between the auditory canals (pol-iamUiamr-por) were reduced. The

petrous temporal bone (petpl-petaVpetar-petpr) angle was within the normal range.

Discussion: The pattern of measurements of the petrous temporal bone differ in this patient with

atresia of the left external auditory meatus from the other patients with Crouzon syndrome. The

sphenoid sutures with the petrous temporal bone were not increased but rather decreased. The jugular foramen was of normal size, (although the trend was for it to be reduced). The sutural

distances laterally were increased or normal. The distance between the petrous temporal bones

was reduced. In summary, the temporal bone measurements demonstrated hypoplasia of the petrous bone with a resultant atresia on the left side.

Page 352 Crouzon Syndrome Figure 3.33(n) Z Scores of the Distances of the Temporal Bone for Patient HC compared with the Adult Experimental Standard

Z score Squamous External Auditory Meatus Zygomatic Process 2 L R L R L R

0 o

-1 o

-J LÈÈ !Ødq !Ødç '=Àoñ'= çoÊÊ5 çoLÈ4 *ddC b É èç ts =Þ.oñ= ä.FÉE CE EtrOÉÈ ç f 8.Ef 3.3. f J-14 q dGjjÈ Í.F k *,8ç õsåE õsåsq E õ 9 Ë- 6 N "€ ç"Êå""å* d= tr= ñi ã ÈE È ã E 9Ñ ËtroÈÈ trtroÈq o ñÉ dd oo oo

Figure 3.33(o) Z Scores of the Measurements of the Temporal Bone for Patient HC compared with the Adult Experimental Standard

Z score Petrous Dimensions Angles 3.00 L R L R 2.00

1.00

0.00

-1.00

-2.00

-3.00

-4.00

-s.00

-6.00

-7.00 qÉ99 ÈèÊÕ.q< EBTS E.À;^q ÉEZZ ;i;ãÈ:aE 9_*ñ Ë Èila úÃño To-r¿ Tb:T !È!Ls's¡P? riÈ+ h¡id+! *F3-,.- E¿çA Ê+ íE E içod * È 8.- I 3 E F sõ E s Qè Ee8,8- !¿a ã. a

Chapter 3 Page 353 3.4.21.L0 The Parietal Bone of Patient HC

Distances: The key landmarks for the parietal bone for Patient HC were not visible due to suture

fusion and could not be reliably estimated. Therefore the parietal bone was not measured and a

pattern profile of Z scores was not generated. The measurement data for the experimental

standard are reported in Appendix2.

3.4.21.11 The Occipital Bone of Patient HC

Distances (Figure 3.33(p)): The distances around the occipital bone and involving the foramen

magnum were not significantly different from the experimental standard except for the medial

temporo-occipital suture-(inferior) (fml-ptsl, jfmr-ptsr), which was increased in length on the

left with a tendency for an increase on the right. The inferior spheno-occipital synchondrosis

length (ptsr-ptsl) was decreased.

Dimensions (Figure 3.33(p)): The dimensions were not significantly different from the experimental standard.

Discussion: The occipital bone suture with the temporal bone was lengthened, the jugular foramen was normal and the spheno-occipital synchondrosis was reduced in length.

Figure 3.33(p) Z Scores of the Measurements of the Occipital Bone for patient HC compared with the Adutt Experimental Standard

Z score Distances 3.00 Dimensions L R 2.00

1.00

0.00

-r.00

-2.00

-3.00

-4.00 o Àq ea.ù Ê I =oJro uo, 'i "l- r+ 31 a a q+.ç* CÚ .*: oo 3Ë+åÊ Þ -o I îo õE.F.E H Þ. o. '-q .- å ¡..8 s.E-3.ts r- o. ç aÀoc)

Page 354 Crouzon Syndrome 3.4.21.12 The Cranial Base Sutures of Patient HC

Anterior Cranial Fossa (Figure 3.33(q)): The spheno-ethmoid synchondrosis (es-cppl, es-cppr) was increased in length. The spheno-frontal sutures in the anterior cranial fossa (cppl-spal, cppr-spar) and orbit (spal-zfsl, spar-zfsr) were normal. The spheno-zygomatic suture (zfsl- gwll, zfsr-gwlr) was increased in length.

Middle Cranial Fossa (Figure 3.33(q)): The sutures were relatively normal with the right inferior sphenoid-petrous temporal suture (fisr-petar) reduced in length.

Posterior Cranial Fossa (Figure 3.33(q)): The Ieft inferior medial temporo-occipital suture

(¡fml-ptsl) was slightly increased in length. Laterally the sutures were not significantly different from the experimental standard. The superior and inferior parts of the spheno-occipital

synchondrosis (petal-petar, ptsl-ptsr) were reduced in length, while the lateral part of the

synchondrosis (ptsl-petal, ptsr-petar) was normal in height.

Discussion: A common pattern of deformity was found in Patient HC, with spheno-ethmoid

synchondrosis length increased medially and zygomatic suture lengthened laterally. The middle

cranial fossa was relatively spared while a mixed pattern of suture deformity was found posteriorly. Lengthening of the spheno-occipital synchondrosis with hypoplasia of the medial

petrous temporal bone was linked with atresia of the external ear canal on the left side.

Figure 3.33(q) Z Scores of the Dimensions of the Cranial Base Sutures for Patient HC compared with the Adult Experimental Standard

Z score Anterior Cranial Fossa Middle Cranial Fossa Posterior Cranial Fossa t2.00 10.00 8.00 6.00 4.00 2.OO 0.00 -2.00 -4.00 -6.00 -8.00

oo-i9RBE3.{iEt siFs*F**-!,¿=Lj

Chapter 3 Page 355 3.4.21.13 The craniofacial Dimensions and Angles of patient HC

Dimensions and Angles (Figure 3.33(r)): The anterior facial height (n-gn) was increased (mouth closed during CT scan). Laterally the height was not significantly different from the

experimental standard. The SNA (s-n-ss) and SNB (s-n-sm) angles were reduced. The cranial

base angle (ba-s-n) was more obtuse in this patient. The cranial base dimensions were not

significantly different from the experimental standard.

Discussion: The cranial base angle was increased in this patient. This may contribute to a reduction in the facial angles. However, the decreased facial angles would be expected due to the maxillary hypoplasia alone. The SNB angle may be decreased due in part to the increased gonial angle of the mandible.

Figure 3.33(r) Z Scores of the Craniofacial Dimensions and Angles for patient

HC compared with the Adult Experimental Standard

Z score Facial heights Facial Angles Cranial Base 4.00 SNA SNB Angle Dimensions 3.00 CI 2.00 r.00 0.00 -l.00 -2.00 -3.00 -4.00 -5.00 k Ê yo o I bo bo \L1 é¿, I _o CÉ -o -o

Page 356 Crouzon Syndrome 3.4.22 Clinical and Radiographic Findings for Patient TS

Clinical Features

This 2l year old man presented from overseas having had no previous surgery and with no family history (Figure 3.8). He had turricephaly, a prominent supra-orbital ridge, with proptosis, hypertelorism, a divergent squint and corneal ulceration with keratitis. Maxillary hypoplasia was present with a class III occlusion. The speech was hypo- and hyper-nasal.

Lateral, Antero-Posterior and Basal Radiographs

LateraI, anterior-posterior and basal views had been performed. The faint outline of the coronal suture could be seen bilaterally. No other cranial sutures were visible. There was a copper- beaten appearance to the calvaria along with a very prominent frontal sinus and frontal gibbosity. The nasal bones were prominent. The lesser wings were swept up with a prominent enlarged sella. The spheno-occipital synchondrosis could not be seen. Extensive aeration of the mastoid air cells was present. The occlusion was class III. The orbital aperture were elongated in the vertical or slightly oblique direction. This was related to the prominent frontal, ethmoid and maxillary sinuses.

3D CT Reconstruction

Calvarial bones: The most striking feature was the prominent supra-orbital ridge, with a relative flattening of the frontal bone above this. The calvarial sutures could not be visualised. The head shape was relatively normal posteriorly.

Cranial base: The cribriform plate and medial frontal bone were clearly very thin and attenuated, and appeared to be pushed down and laterally. This produced the impression of excessive endocranial bone resorption in this region. Anteriorly, there was an impression in the bone of the anterior cranial fossa made by the globes of the orbit, suggesting a constriction of the orbit by the frontal bone. The sella appeared relatively narrowed. Posteriorly the clivus was steep.

The petrous temporal bones were not prominent, and gave the impression of being affected by bone resorption as well. The foramen magnum was unremarkable. The posterior cranial fossa showed areas of thin attenuated bone. The mastoid prominences were enlarged.

Chapter j Page 357 Orbital: The orbital shape was oblique, being narrowed medially by protrusion of the lateral

ethmoid plate into the orbit. Laterally, the opening of the orbit was increased in height. The roof

had a serpentine appearance, being pushed downwards posteriorly and curving upwards and

forwards in its anterior half. The greater wing of the sphenoid was prominent in the lateral wall

of the orbit. The superior orbital fissure was reduced in length.

Maxilla and Mandible: The maxilla appeared to be narrowed with poor anterior projection and

the typical class III occlusion. The height of the maxilla appeared to be normal. The anterior

nasal spine was prominent along with the nasal bones and naso-frontal processes of the

maxilla. The size of the nasal aperture was subsequently reduced. The zygomatic bone appeared

to be small at the region of the zygo-maxlllary suture, while the frontal process was increased in

height. The angles of the mandible were prominent laterally.

3.4.23 Features of CT Scan and 3D Reconstruction of Patient TS that made landmark identification difficult

While this patient showed several areas of bony resorption on the internal cranial skeleton,

increased growth or bony apposition was found externally. Bony prominences included the

frontal supra-orbital ridge, the mastoid processes, para-nasal bones and the gonial angles of the

mandible. The frontal and mastoid regions were associated with increased sinus air cells.

Repeated 3D CT reconstruction at a lower threshold did not remove the bony defects entirely,

implying the bone was thin and attenuated. Lower threshold CT scan reconstruction began to

occlude foraminae in the cranial base and orbit. The calvarial landmarks (1, as, br, spt, spc)

could not be identified nor reliably estimated. The peri-orbital sutures and cranial base landmarks were identihed from the regional bony contours and junctions defined in the landmarks (Figures 3.I5-3.26).

Page 358 Crouzon Syndrome 3.4.24 Results and Discussion of the Quantitative Analysis of Patient TS compared with the Adult Experimental Standard

Figures 3.34(a)-(r)

Chapter 3 Page 359 3.4.24.1 The Mandible of Patient TS

Distances (Figure 3.34(a)): The left superior body distance (id-cbl) was increased, and the left

anterior ramal height (cbl-ctl) was increased compared with the experimental standard. The left

inferior body distance (gol-gn) was increased. The distances on the right hand side were not

significantly different from the experimental standard.

Dimensions andAngles (Figure 3.3a(b)): The intergonial distance (gol-gor) and the distance

between the coronoid bases (cbl-cdr) was increased. The anterior symphyseal height (gn-id)

was increased. The total length of the mandible (gn-cdl) on the left was increased. The right

coronoid base angle (ctr-cdr-id) was significantly reduced. The anterior mandibular angle (gol-

gn-gor) was significantly increased.

Discussion: Deformity around the region of the angle was pronounced in this patient. The

gonial angles were flared out laterally although the measurement of the angles (cd-go-gn)

themselves were not changed. The anterior symphyseal height was increased in a similar

manner to the other three older patients (see Patients LW, Ay and HC).

Page 360 Crouzon Syndrome Figure 3.34(a) Z Scores of the Distances of the Mandible for Patient TS compared with the Adult Experimental Standard

Z score L R 3.00

200

1.00

0.00

-1.00

-2.00 .o.oiEúOL-^ ??JE9PÏ Èë ë Ë EÈ H, t" q) 'õ.i-: I ='=õËËEY"E. 5ËÈëEEtþ" o

Figure 3.34(b) Z Scores of the Dimensions and Angles of the Mandible for Patient TS compared with the Adult Experimental Standard

Zscore Dimensions Angles 6.00

5.00

4.00

3.00

2.00

1.00

0.00

-1.00

-2.00 !ÈÊÊ 't!cÉ.o'ú=.:'o.o! o!,o= a -o o .o .:€r ou{æiT--i19^ @ooa rts ''ÉcçÈï" o!¡q) o ! ÐÉÉ Ë!ã:45 èo o { u {ooJ O il sEiF:T;iåË-? tr rkç€oõo*aðO o úEoõ-É;* o

Chapter 3 Page 361 3.4.24.2 The Maxilla of Patient TS

Distances (Figure 3.34(c)): The anterior lateral orbital floor distance (orl-iobfl, orr-iobfr) was

reduced bilaterally compared with the experimental standard. The maxillary orbital rim distance

(orl-nlil, orr-nlir) was increased bilaterally. The right anterior border of the lateral ethmoid plate

(nlir-mon) was reduced. The left lateral distance (zmil-emlsl) was increased on the left. The

anterior alveolar margin (emlsl-pr) on the left was reduced, but normal on the right. The naso- maxillary suture length (inml-snml, (inmr-snmr) was increased bilaterally. The anterior alveolar height (pr-ans) was increased. The posterior alveolar margin (emlsl-mxtl) on the left was increased in length, but normal on the right. The posterior maxillary wall height (mxtl-msl, mxtr-msr) was significantly increased bilaterally. The palatal distances were normal.

Dimensions and Angles (Figure 3.3a(d)): The dimensions representing the height of the maxilla were significantly increased (n-pr, morl-emlsl, morr-emlsr, gpfl-msl). The widths of the maxilla were normal except for the superior (inter-orbital) width (orl-on) which was increased.

The height of the nasal aperture (na-ans) was reduced. The measured angles of the rnaxilla were normal.

Discussion: The height of the maxilla was generally greater than for the experimental standard.

Measurements recorded in the anterior-posterior direction were normal or reduced. The position of the molar teeth from the prosthion was reduced suggesting crowding of the dental arch. The measurements reflect a lack of anterior development of the maxilla with an over-development in the vertical direction.

Page 362 Crouzon Syndrome Figure 3.34(c) Z Scores of the Distances of the Maxilla for Patient TS compared with the Adult Experimental Standard

Zscore Orbital Anterior Lateral Palatal 6.00 R 5.00 L L R L R LR 4.00 3.00 o 2.00 1.00 0.00 -1.00 -2.00

-3.00 -4.00

E h .H ,.: ,t.! ø o o 6 ô= ô o ¡ ô= ôJ *6 tÈ ! d= É d É x c¡ E Ê tr = ì o oi = Þo È q I E * ¿.8 ã tr '.Y N s+ ¿ ¡:4 ¿ J! E I É ã +.r E I ä¡ J. -:. eJ ) E ã!: N= C dtr N.H =F õ E !ãEg È Ec-Eo E=EÉb- io= ÊEË c Ec Q F" E E E tr

Figure 3.34(d) Z Scores of the Dimensions and Angles of the Maxilla for Patient TS compared with the Adult Experimental Standard

Zscore Dimensions Angles 5.00

4.00

<) 3.00

2.00

t.00

0.00

-1.00

-2.00

-3.00 Þ p¡ d d o o ccchHcc=!PEEEÈ.çËËçI oo4c =,=Ø Àq :¿aqg9Þ Þ Ë+= rÉ¿ ¿E ÉR -a¿q9 i¿ ëcçç õEEEÉ, E E 6õüE Ê fru F !tsoo boo 'iE EE lL4ú EÀ EE =ÉÉdcE!!dd :trÈc'i¿r :cÉdd

Chapter 3 Page 363 3.4.24.3 The Nasal Bones of Patient TS

Distances. Dimensions and Angles (Figure 3.34(e)): The length of the naso-maxillary sutures

(inml-snml, inmt-snmr) were increased bilaterally. The width of the nasal bones was not

significantþ different from the experimental standard, however, the angle from the cranial base

(s-n-na) was decreased.

Discussion: The nasal bones were increased in length and were at an inferiorly placed angle

from the cranial base skeleton. The inferiorly placed angle of the nasal bones corresponds with

the lack of anterior projection of the maxilla and increased vertical height of the maxilla (see maxilla).

Page 364 Crouzon Syndrome Figure 3.34(e) Z Scores of the Measurements of the Nasal Bones for Patient TS compared with the Adult Experimental Standard

Z score L Distances R Dimensions Angles 7.00 a--- 6.00 5.00 4.00 3.00 2.00 1.00 0.00 -l.00 -2.00 -3.00 -4.00 Ê Ê d Þ E E Ei E; É àé É õ h ñ É EE Ê .áâ

Chapter 3 Page 365 3.4.24.4 The Frontal Bone of Patient TS

Distances (Figure 3.3a(Ð):

Supra-orbital Region: The majority of measurements were not significantly different from the

experimental standard with the exception of the increased dist¿nce of the superior lateral orbital rim (sorl-slorl, sorr-slon) bilaterally.

Ethmoid Attachment: Significant discrepancies were found in the region of the ethmoid. The fronto-ethmoid articulation was reduced in length in the anterior cranial fossa (cpal-cppl, cpar- cppr). The width however, was significantly increased anteriorly (fc-cpal, fc-cpar) and posteriorly (cppl-ofaml, cppr-ofamr). These findings were in direct contrast to the findings in Patient HC

Sphenoid Attachment: The lesser wing length was increased on the right (spar-cppr). The remaining suture distances of the fronto-sphenoid junction were not significantly different from the experimental standard. The parietal at[achment (spc-br) and sphenoid attachments (zfs-spc and spc-spa) were not recorded due to the fusion of sutures and hence poor visibility of landmarks in this region.

Dimensions (Figure 3 3a(f): The medial prominence (g-n, s-g) and depth of the anterior cranial fossa (sorl-spal, sorr-spar) of the frontal bone was within the experimental standard range. The anterior supero-lateral orbital width (slorl-slorr) of the frontal bone was significantly increased compared with the experimental standard. The posterior width between the tips of the lesser wings (spal-spar) was significantly increased.

Discussion: The deformity in this patient can be localised to the frontal ethmoid region and antero-laterally to the region of the fronto-zygomatic and calvarial articulations. The role of the sphenoid lesser wing in the production of the frontal bone deformity was not great, as determined from the measurements. The broad frontal ethmoid attachment with a reduced length was not seen in the other patients. Fusion of the sutures lateral to the spheno-ethmoid synchondrosis and cribriform plate at the frontal ethmoid atlachment could produce this pattern of deformity. The calvarial suture abnormalities seen qualitatively, contributed to the distortion of the lateral orbital rim and influenced the morphology of the frontal bone.

Page 366 Crouzon Syndrome raJ N I oa A N) O N) è o\ æØ b b b8 ã O O o l+r (, n-snml I snml-morl I I À morl-sorl - FÚî sorl-slorl U) slorl-2fl ¡oÉ zf7-zfsl I 9N I r-f zfsl-slorl o (h + rlô n-snm¡ V); snmr-morr X^O lt) morr-solr solr-slorr 30 slorr-zfr A¡ r+ zfr-zfsr zfsr-slorr tÌAiD ì! ¡. n-fc o r-. (t

fc-cpal cpal-cppl - (Þi; cppl-ofaml FI morl-ofaml Èa fc-cpar a. cpar-cpp¡ cPpr-ofamr morf-ofamr xË ìõo(DÞ ã(h ofaml-sobfl sobfl-zfsl U) - (t spal-cppl ;¡ o ofarff-sobfr I F è sobfr-zfsr I v)9 Õ spar-cppr Ðo \S cs g-n ì s-g sorl-spal ciã 3 Þ sorr-spaf o sorl-sorr Ø Oa slorl-slorr Ø ({ spal-spar o \o\ 3.4.24.5 The Zygomatic Bone of Patient TS

Distances (Figure 3.3a(g)): The orbital zygo-maxillary suture (orl-iobfl, orr-iobfr) was reduced

in length bilaterally compared with the experimental standard. The inferior orbital fissure height

(iobfl-gwll, iobfr-gwlr) was also reduced. The spheno-zygomatic suture (gwll-zfsl, gwlr-zfsr) was increased in length bilaterally. The lateral height of the frontal process was decreased (zfr-

ztr) on the right side. On the left side, the inferior length of the zygomatic arch (parl-zmil) was reduced and the zygomatico-temporal suture (ztl-parl) was increased. A similar trend was seen on the right side.

Dimensions (Figure 33aGÐ: The height of the zygomatic bone (slorr-zmir) was increased on the right compared with the experimental standard with a similar trend on the left. The lengths of the left and right zygomatic bones (parl-orl, parr-orr) also showed a trend to be reduced, but were not statistically significant.

Discussion: The pattern of morphology of the zygomatic bone appeared to be determined by the spheno-zygomatic suture. This suture was increased in length and was presumed to be fused.

The development of the zygomatic bone was therefore reduced in the AP direction with an increase in dimensions in the vertical direction.

Figure 33a(g) Z Scores of the Distances and Dimensions of the Zygomatic Bone for Patient TS compared with the Adutt Experimental Standard

Distances Dimensions I 1.00 L R 9.00

7.00

5.00

3.00

1.00

-1.00

-3.00

-5.00

ÈLF E=EEFEEEEEEEE EEEbteãbbiã;3 '=.-ÈLLUtitrôôoô .9dæ;+N='ïãlÈñ-l if*.É=l ¡Ë*€+FEEË**ËF Ë 5 å3.E"; ËËt*å*:ËË*sÈË Ø-;q¿Ð

Page 368 Crouzon Syndrome 3.4.24.6 The Vomerine Bone of Patient TS

Distances. Dimensions and Angles (Figure 3.3aft)): The length of the spheno-vomerine junction (h-ves) was reduced. The remaining distances were not significantly different from the

experimental standard. The longitudinal dimension was normal. The angle of the vomer (s-n/h-

ans) relative to the cranial base was significantly increased.

Discussion: In this patient the vomer showed a mild tendency to be smaller and was angled

further inferiorly. This corresponds with a lack of forward growth of the vomer and may direct

the position of the maxilla.

Figure 3.34(h) Z Scores of the Measurements of the Vomer for Patient TS compared with the Adult Experimental Standard

Z score Distances Dimension & Angle 3.00 2.00

1.00

0.00

- r.00

-2.00 -3.00 Efú'03 (! cd pÞ.-cíi'õ??ìiç I I ã>>

Chaprer 3 Page 369 3.4.24.7 The Ethmoid Bone of patient TS

Lateral Ethmoid Plate (Figure 3.3a(i)):

Distances: The lateral ethmoid plate distances, forming the medial orbital wall, were reduced in height but not in length. The height of the medial orbital wall posteriorly (ofaml-msl, ofamr- msr) was reduced bilaterally and the anterior border of the lateral plate (nlir-morr) was reduced on the right side. The posterior frontal ethmoid attachment (cppl-ofaml, cppr-ofamr) was increased in distance bilaterally.

Dimensions and Angles: The inter-orbital distance (morl-mon) and posteriorly between the optic canals (ofaml-ofamr) were significantly increased. The splay of the lateral plate was decreased anteriorly (ulil-morVmorr-nlir), however was increased posteriorly (msl- ofamVofamr-msr).

Cribriform Plate (Figure 3.34j):

Distances: The anterior cribriform plate width (fc-cpal, fc-cpar) was increased bilaterally. The posterior widths at the spheno-ethmoid synchondrosis (es-cppl, es-cppr) were not significantly different from the experimental standard. The length of the cribriform plate was reduced bilaterally (cppl-cpal, cppr-cpar).

Angles: The cribriform plate lateral angles (s-n/cpal-cppl, s-n/cpar-cppr) were increased signihcantly.

Medial Ethmoid Plate (Figure 33a):

Distances: The spheno-ethmoid junction (es-ves) and the septal junction (vei-n) were increased

Dimensions: The height of the medial plate (vei-cg) was increased.

Discussion: The lateral plate was reduced in height. The cribriform plate showed an inc¡ease in width anteriorly and decreased length, while the medial plate was increased in height. The spheno-ethmoid synchondrosis was not involved in this patient however the frontal ethmoid attachment was increased in width (see frontal bone). The splay of the lateral plates anteriorly, but not posteriorly, were decreased. Normal growth at the spheno-ethmoid synchondrosis would fit with the more normal posterior splay to the lateral plate. The spheno-ethmoid synchondrosis, when involved in the pathology, appears to push the superior part of the lateral plates further laterally and thus decreasing the angle of lateral splay.

Page 370 Crouzon Syndronrc Figure 3.34(i) Z Scores of the Measurements of the Lateral Ethmoid Plate for Patient TS compared with the Adult Experimental Standard

Z score Distances Dimensions & Angles 5.00 Medial orbital wall Frontal ethmoid attachment 4.00 ______t R- _I= -R

3.00

z.o0

1.00

0.00

-1.00

-2.00

-3.00

!É2.- xÉ4= E :ãHÊ Eù la È ,r HÊ:ãÊb ,rçV?, J9>á È o E o ?x Ë ÈË Ëq À HEE'E Éo E À ç,õ.-- O tr.d =T E

Figure 3.34(i) Z Scores of the Measurements of the Cribriform and Medial Ethmoid Plates for Patient TS compared with the Adult Experimental Standard

Zscore Cribriform plate Medial plate 6.00 Distances Angles Distances Dimensions L R 4.00

2.00

0.00

-2.00

-4.00 !ã.ã çqd èdÈ VU+Èo oò Jr+,t eb¿Yoo ?Y{ åo äu ìèÈqÉ

Chapter 3 Page 37 I 3.4.24.8 The Sphenoid Bone of Patient TS

Lesser'Wing (Figure 3.3aG)):

Distances: The medial part of the lesser wing (ofaml-acl, ofamr-acr) was reduced in length

compared with the experimental standard. The posterior length of the lesser wing (acl-spal) on

the left and the anterior length of the lesser wing (spal-es, spar-es) bilaterally were increased.

Dimensions and Angles: The distance between the tips of the lesser wing was increased (spal-

spar), with an increase in the angle between the lesser wings (spal-es-spar). The other distances and angles of the lesser wings were not significantly different from the experimental standard.

Pterygoid Plate (Figure 3.3a(k)):

Distances and Angles: The pterygoid plate distances were not significantly different from the experimental standard. The angles of pterygoid axis, however, were significantly increased (s- n/ptsl-hpl, s-niptsr-hpr) .

Greater Wing (Figure 3.3aO):

Distances: The lateral and orbital distances were nonnal with the exception of the spheno- zygomatic suture (zfsl-gwll, zfsr-gwlr) which was increased in length bilaterally (see zygomatic bone). The distance of the anterior floor of the middle cranial fossa was increased (fosr-gwlr) on the right. The length of the inferior orbital greater wing of sphenoid was reduced (gwml- gwll) on the left with a similar trend on the right. The posterior part of the greater wing was increased at the posterior floor of the middle cranial fossa (fosl-petal) on the left side (adjacent the spheno-petrous temporal suture (superior) (fisl-petal). Landmarks on the squamous sphenoid bone (spt and spc) could not be identified bilaterally, due to fusion of the calvarial bone in this region and hence the distances of the lateral part of the bone could not be measured.

Dimension and Angles: While the angles of protrusion of the greater wing were increased (zfsl- gwml/gwmr-zfsr, gwll-gwml /gwmr-gwlr), the angle of the floor of the greater wing was normal (zfsl-gwml-ptsl, zfsr-gwmr-ptsr). The remainder of the distances and angles were normal.

Page 372 Crouzon Syndrome Figure 3.34(k) Z Scores of the Measurements of the Lesser Wing and Pterygoid Plate of the Sphenoid for Patient TS compared with the Adult Experimental Standard

Zscore Lesser rJy'ing Pterygoid plate 6.00 Distances & Angles Distances Angles L R L R 4,00

2.00

0.00

-2.00

-4.00

-6.00 L L kkkk O(d;i O d .r dcdcd¿d- a.É!o Ê. Ê. cÉô-Y cd O. -l o. o. Þ. o. .É ,E o. _O t9 -ato-oll'9 t-clt + ?ã ØØØØlr LL¿r EiF Ø4k I qÊ= Øõ-?H Hç * 89 H H Þ.!-cä o.e -ç o¡ o- o "EHão ØE>> Ë Bå ¿ tt

Figure 3.34(t) Z Scores of the Measurements of the Greater Wing of the Sphenoid for Patient TS compared with the Adult Experirnental Standard

Zscore Lateral Orbital Posterior Dimensions & Angles t2.00 ï R L R L R 10.00

8.00

6.00

4.00

2.00

0.00

-2.00

-4.00

È¡ç ô 'ú?¿ Èord Èo É -"5 5 q vi 'ú4.i ìJ ¡âL FÊ4Úd I ,9, ¿Éã ,Ò9 i < > E> q ùN üN e € - t5øío E5eqa 1 a E * EE -Ë. .Ø.òqúi) L l¿û- .'ln'ñ+ ' .r q @3

Chapter 3 Page j73 3.4.24.8 The Sphenoid Bone of Patient TS (continued)

Body of Sohenoid (Figure 3.34(m)):

Distances: The lateral distances were not significantly different from the experimental standard with the exception of the increased anterior inferior margin of the sphenoid body (gwml-ptsl, gwmr-ptsr). The lateral height of the spheno-occipital synchondrosis bilaterally (ptsl-petal, ptsr- petar) was normal. The anterior body distances at the spheno-ethmoid synchondrosis (es-cppl, es-cppr) were normal, while the anterior superior length (ofamr-gwmr) on the right was reduced. The posterior border of the frontal ethmoid atüachment (cppl-ofaml, cppr-ofamr) was increased. The distances of the floor were increased at the spheno-ethmoid medial plate junction

(es-ves), reduced at the $pheno-vomerine junction (h-ves) and increased in width on the left posterior side (ptsl-h).

Dimensions: The dimensions revealed an increased distance at the anterior inferior body (gwml- gwmr) and the anterior superior body width (ofaml-ofamr) between the anterior optic foramina.

The superior spheno-occipital synchondrosis (petal-petar) was reduced in length while the inferior spheno-occipital synchondrosis (ptsl-ptsr) was norrnal (see cranial base sutures). The height of the anterior body was reduced on the right side (acr-gwmr). The angles of the lateral protrusion of the body from the midline were reduced bilaterally (s-n/ofpml-petal, s-n/ofpmr- petar).

Discussion: This sphenoid bone in this patient had stightly enlarged lesser wings. The spheno- ethmoid synchondrosis was normal, but there was deformity lateral to this with broadening of the anterior sphenoid, frontal and lateral ethmoid junctions. An increased angle of protrusion of the greater wings was present with lengthening of the spheno-zygomatic sutures and some of the spheno-temporal sutures. The region around the spheno-occipital synchondrosis was normal or reduced in length. The pattern of deformity of the body was of an increase in width of the body anteriorly and inferiorly with the posterior portion remaining relatively normal.

Page 374 Crouzon Syndronrc fal 0a I I I I N -l (^ fJ) (¿) urØ O ;-C) ã o O O o (D OJ gwml-Pßl i, Ptsl-petal f. t- l+l A petal-pcl Þ (Þ Þ5 ä Þ¡ pcl-pcr ã.v o Ø r+N gwmr-ptsr o ¡l Ptsr-peta¡ F ú? petar-pcr Xã (t) es-cpPl =oË cppl-ofaml l- Fl ofaml-gwml (!(+ (þ ã ÈÈ'o es-cPPr no cppr-ofamr F i+È ofarnr-gwmr sl !+=ro (t) cppl-ofpml (Dã5Ë ofpml-petal l' (t) o Pã-ô cppr-ofpmr F¡ +ã ofpmr-petar aÞ ct) es-ves N lâ .D xÉ h-ves E(DÉ h-ptsl o FIP h-ptsr I o I I tÞ ttl gwml-gwmr 50 ptsl-ptsr bcL U Ê¡ << ofaml-ofamr 5 o Petal-petar I pcl-ptsl I Ø ?g Õ I I o pcr-Ptsr I t+ I Ø ÊiD acl-gwml !¡ -: acr-gwmr ãv) ({ Èlã es-ves-h o s-n/gwml-ptsl 0q o s-n/gwmr-ptsr o OA(\ s-n/ofpml-petal ({ s-n/oþmr-petar o LI\ ã 3.4.24.9 The Temporal Bone of Patient TS

Distances (Figure 3.34(n)) :

Squamous Temporal Bone: The squamous temporal bone was not fully measurable in this child due to lack of visibility of the asterion (as) and sphenion (spt). The remaining distance of medial mastoid prominence (mal-smfl, mar-smfr) was increased bilaterally.

External Auditory Meatus: The lateral mastoid prominence (mal-eamil, mar-eamfu) from the external auditory meatus was increased. The anterior inferior rim (eamal-eamil, eamar-eamir) bilaterally and the right inferior posterior rim (eamir-eampr) were reduced in length.

Zygomatic Process: The zygomatic process was generally within the normal range and symmetrical. The zygomatico-temporal suture distance (ztl-parl) was increased on the left. The height of the articular fossa (afl-ael, afr-aer) was normal.

Petrous Temporal Bone (Figure 3.34(o)): A trend at the apex of the petrous ridge was identified from the pattern profiles. The sphenoid-petrous temporal suture (fisr-petar) was significantly increased in length on the right, with a relative trend to be increased on the left. The petrous temporal-occipital suture length (petal-jfpl) was reduced on the left with a relative trend to be reduced on the right. The jugular foramen width was not significantly different from the experimental standard (fll-jfml, jfu-jfmr). Increased distance of the occipital mastoid suture

(mal-jfll) was found on the left side.

Dimensions (Figure 3.34(o)): The petrous temporal ridge dimension (petal-petpl, petar-petpr) was increased in length bilaterally. The distances between the internal auditory meati points

(iaml-iamr) and the jugular foramina (fpl-jfpr) were normal, with significantly increased distances between the porion points (pol-por). The measured angles were not signihcantly different.

Discussion: The mastoid process was prominent in this patient with some minor discrepancies in the region of the external auditory meatus. The increased zygomatico-temporal suture length contributes to the increased height and reduced length of the zygomatic bone (see zygomatic bone). The abnormality of the petrous temporal bone was more complex. Increased suture lengths were identihed medially with the sphenoid bone and laterally with the occipital bone.

Tl-re jugular foramen, however, was normal in this patient.

Page 376 Crouzon Syndrome Figure 3.34(n) Z Scores of the Distances of the Temporal Bone for Patient TS compared with the Adult Experimental Standard

Zscore Squamous External Auditory Meatus Zygomatic Process 4 L R L R L R J o o 2

-J

!Ø6ç !ødç ñ= ç0ÊLd çok!á *f E E rddé E tr oË ts =Èci ts dñççñ :-tq cç E tr oÉ ç f 33.f q dçl;e *E ü3Ë"3ü õ E È.s E d 9Ë * ßç! Ñ Ë E 33rã ã+E+ã EÈ ã E 9Ë tr trÈootr ã: o dñ trÈoatr o oo ddoo

Figure 3.34(o) Z Scores of the Measurements of the Temporal Bone for Patient TS compared with the Adult Experimental Standard

Z score Petrous Dimensions Angles 5.00 L R L R

4.00

3.00

2.00

1.00

0.00

-1.00 .A¿

-2.00

ñô=d ñ d.= d qEE*E* -c Èllo õ=,äõ .r' I O o ç'P83.ÊÊ &ÊFF j.dq¿ õ-õ-1-l¿-a LèI -IdÈf EÉylË bG¿9 E,i-ç.9 E Ë E eÊ Ê ddl¿ ùo Ee8"8-\;, li 8-+ E. È

Chapter 3 Page 377 3.4.24.L0 The Parietal Bone of patient TS

Distances: The key landmarks for the parietal bone for Patient TS were not visible due to suture

fusion and could not be reliably estimated. Therefore the parietal bone was not measured and a

pattern profile of Z scores was not generated. The measurement data for the adult experimental standard are reported in AppendixZ.

3.4.24.1L The Occipital Bone of Patient TS

Distances (Figure 3.34(p)): The distances around the occipital bone were not significantly

different from the experimental standard, including the medial temporo-occipital suture (fml-

ptsl, jfmr-ptsr). The spheno-occipital synchondrosis was discussed elsewhere (see sphenoid

bone and cranial base sutures). The foramen magnum appeared to be slightly increased in size,

with significant increases in length of the left anterior and posterior foramen magnum (ba-fmll, fmll-o).

Dimensions (Figure 33a(p)): The width of the foramen magnum (fmll-fmlr) was significantly

increased. The posterior cranial fossa depth (o-iop) was increased in size and the left posterior fossa length (petpl-iop) was increased.

Discussion: The occipital bone was enlarged at the foramen magnum. The lambdoid sutures could not be measured, however, it appeared calvarial distortion would account for the shape changes to the occipital bone shape.

Page 378 Crouzon Syndrome Figure 334(p) Z Scores of the Measurements of the Occipital Bone for Patient TS compared with the Adutt Experimental Standard

Z score Distances Dimensions 3.00 L R 2.00

1.00

0.00 o -1.00

-2.O0 H q k o o AQ -Ê-+Ê I I oo çEÊ,EE* È ç ,t .E '1oo. 3 ËE'ä Ê I I I -o I 0 ¿ k (d .ú q= -r. o. õÉFE KË.åË .o .o o¡ or Èqoo

Chapter 3 Page 379 3.4.24.12 The Cranial Base Sutures of patient TS

Anterior Cranial Fossa (Figure 3.3a(q)): The spheno-ethmoid synchondrosis (es-cppl, es-cppr) was of normal length. The spheno-frontal sutures (cppl-spal, cppr-spar) in the anterior cranial fossa show a tendency to be increased and in the orbit (spal-zfsl, spar-zfsr), tend to be reduced.

The spheno-zygomatic suture (zfsl-gwll, zfsr-gwlr) was increased in length.

Middle Cranial Fossa (Figure 3.3a(q)): The sutures were relatively normal with the right sphenoid-petrous temporal suture (inferior) (fisr-petar) increased.

Posterior Cranial Fossa (Figure 3.3a(q)): The lateral occipital mastoid suture (flI-petpl, jflr- petpr) was increased in length. Laterally the sutures were not significantly different from the experimental standard. The superior part of the spheno-occipital synchondrosis (petal-petar) was reduced in length, while the inferior and lateral parts of the synchondrosis (ptsl-ptsr, ptsl- petal, ptsr-petar) were normal in length and height.

Discussion: The spheno-ethmoid synchondrosis was of normal length. The cranial base sutures were abnormal lateral to the spheno-ethmoid synchondrosis at the frontal ethmoid attachment

(see frontal and ethmoid bones). Laterally the spheno-zygomatic suture was abnormal and likely represented a continuation of the calvarial suture abnormality identified qualitatively.

Posteriorly the sutural abnormality was identified medially at the spheno-temporal and laterally at the occipital mastoid sutures but did not greatly deform the temporal and occipital bones.

Medially the spheno-occipital synchondrosis was deformed with a reduced superior width.

Page 380 Crouzon Syndrome Figure 33a(Q Z Scores of the Dimensions of the Cranial Base Sutures for Patient TS compared with the Adult Experimental Standard

Z score Anterior Cranial Fossa Middle Cranial Fossa Posterior Cranial Fossa 10.00

8.00 6.00 4.00 2.00

0.00 -2.00

-4.00 -6.00 ØØcüdØØLÈ!ÊL çÉ,ØØo.o.(dØ(Ú(Úk-Þ-!9L-L 'Hrtsrq)6)o.o. :.11 :i1 Ê. o. () o a o. () o FsBH.çrãä + È + +J ¿ ú >*ã"EËÉr ã FË È -? 1g+ 3 i 'E +E ** Ë ËÞÈËEÉËäE-g-

Chapter 3 Page 381 3.4.24.13 The Craniofacial Dimensions and Angles of Patient TS

Dimensions and Angles (Figure 3.34(r)): The anterior facial height (n-gn) was increased. The

SNA (s-n-ss) and SNB (s-n-sm) angles were reduced. The cranial base dimensions were not significantly different from the experimental standard. The cranial base angle (ba-s-na) was increased in this patient.

Discussion: The cranial base angle was increased in this patient. The platybasia may reduce the facial angles and was also seen in Patients HC and IP. The cause of the cranial base angle increase is not evident from the measurements.

Figure 3.34(r) Z Scores of the Craniofacial Dimensions and Angles for Patient TS compared with the Adult Experimental Standard

Zscorc Facial heights Facial Angles Cranial Base 6.00 5.00 -sNA - -SN-B- - - - - Angle- _pi_r4e_ngi_o¡g____ 4.00 3.00 ö 2.00 1.00 0.00 -1.00 -2.00 -3.00 -4.00 eÅ -5.00 Þ É bo o o èo Þo I F?ç I I I ,b .8S,h I .o

Page 382 Crouzon Syndrome Table 3.3 Summary of Morphological Findings for Eight Patients with Crouzon Syndrome

Ch.apter 3 Page 383 Table 3.3. SUMMARY OF MORPHOLOGICAL FTNDINGS

BONE & Patient RN Patient SH Patient JS Patient IP REGION . MANDIBLE majority normal . majority normal . majority normal . I intercondylar distance . I gonial angle

MAXILLA . Orbital . I orbital angle . widened orbital . normal . broad frontal process apex (t sup. . I orbital length maxillary splay) . broad orbital rim

Anterior . { depth . normal . I ant. zygo-maxillary o I ant. zygo-maxillary . I rim size suture suture . I heieht of maxilla . . . Lateral 1 post. zygo- normal . I maxillary . 1 post. zygo-maxillary maxillary suture tuberosity height suture . I height of maxilla . t width maxilla superiorly Palatal . I palatal angle . I palatal angles . I palatal length . relatively normal . narrow palatal ansles . NASAL t nasomaxillary . t nasomaxillary . I frontal width . all nasal lengths I length (L) length . broad inferiorly with . broad with J splay & . broad inferiorly ,1, splay inferiorly projection

FRONTAL . Calvarial . not recorded . not recorded . not recorded . not recorded . Supraorbital . mild shape . mild shape . mild shape distortion . severe shape distortion Region d is tortion distortion . sup. lat. orbital . sup. orbital points . sup. orbital . sup. orbital points laterally laterally points laterally points medially .lwidth&{ant.cranial . I naso-frontal fossa depth suture . I fronto- zygomatic suturc Ethmoid . I Iength frontal . normal . I Iength frontal . broad anteriorly Attachment ethmoid ethmoid attachment . J length attachment . I widrh

Sphenoid .f lesser wing .I sup. orbital . normal . I sup. orbital fissure Attachment attachment fissure length . I spheno-frontal suture . . ZYGOMATIC I spheno- 1 fronto- . zygo-maxillary suture . I spheno-zygomatic zygomatic suture zygomatrc suture lengthened suture length length . I fronto-zygomatic suture but less severe

VOMER . normal . normal . normal . ansled inferiorlv ETHMOID . Lateral plate . broad anteriorly . slightly broad . narrow posteriorly . significantly ,l size of . narTow anteriorly . I height and length plate pos teriorly . broad anteriorly

. Cribriform t length frontal . normal . I length frontal . I width anteriorly and plate ethmoid ethmoid attachment posteriorly (spheno- attachment ethmoid synchondrosis) . Medial plate . normal . normal . f length . t height

SPHENOID . Lesser wing . I length swept . minima.l . broad & splayed . I length up anteriorly distortion laterally . swept up . Pterygoid noftnal . normal . normal . ] size (L) plate . splayed posteriorly & laterally

Page 384 Crouzon Syndrome Table 3.3. SUMMARY OF MORPHOLOGICAL FINDINGS continued:

Patient LW Patient AY Patient HC Patient TS

. majority normal . ant. molar . majority normal . laterally displaced gonial . I symphyseal height . narrow ant. mandible . I intercondylar dist. angles . I symphyseal height . ,1, intercoronoid base dist . (f intergonial distance) . I gonial angles . I symphyseal height . (gonial gibbosity) . I gonial angles . I symphyseal heieht

. short broad frontal . broad frontal process . 1 inf. orbital fissure length . I inf. orbital fissure process . 1 lat. orbital length . broad orbital rim medially length . hypoplastic orbital rim . broad orbital rim . broad orbital rim . I orbital floor ansle (L) . I orbital ansle (L) . I ant. zygo-max. suture . ant. molar . ant. molar . I ant. alveolar height . prominent naso-maxilla . I height of nasal aperture . I height of nasal aperture . I heisht of maxilla . I ant. alveolar heisht . t height of maxilla . I post. height (R) . I lat. & post. maxillary . I lat. & post. heights . broad superiorly . I sup. dimension heights (R) . I ant. sup. width of . 1 post. maxillary angle . I post. maxillary angle . I angles between sup., maxilla (L) oalatal & occlusal olanes . I palatal length . ant. molar . I maxillary arch angle . normal measurements . J palatal angle . . J, naso-max. le¡gth (R) t naso-frontal length (R) . I length of midline . I naso-maxillary length . narrow superiorly . borderline ,1, widths . nasal bones angled . t angle nasal prominence . ¡ nasal/cranial base angle inferiorly (f nasal/cranial . I lateral splay base angle)

. not recorded . not recorded . not recorded . not recorded . mild shape disto¡tion . minimal shape distortion . mild shape distortion . mild shape distortion . I fronto-maxillary suture . widening of naso & . sup. orbital points laterally . sup. lat. orbital points . sup. orbital points lateral maxillary frontal region . 1 width anteriorly & laterally . t width anteriorly & . I fronto-zygomatic posteriorly in ant. cranial . I width anteriorly & posteriorly in ant. cranial suture fossa posteriorly in ant. cranial fossa . I width anteriorly . I depth foss a

.t length frontal ethmoid . normal . I length frontal ethmoid . I length frontal ethmoid attachment attachment but narrowed attachment . slightly narrow . I width anterior oosterio¡lv cribriform plate . I sup.orbital fissure . I sup.orbital fissure (L) . J borderline sup. orbital . I spheno-frontal suture . I spheno-frontal suture . { spheno-frontal suture fissure (L) (cranial R) (cranial) . ¡ spheno-frontal suture (cranial) . I fronto-zygomatic suture . I fronto-zygomatic . t spheno-zygomatic suture . I spheno-zygomatic . I spheno-zygomatic and suture . j zygo-maxillary suture suture zygo-max. suture length . t zygo-temp. suture (R) . { projection of zygoma . (f height l, length of . I lat. height of zygoma zygomatic bone)

. aneled anteriorlv . ansled slishtly ant. . aneled inferiorlv . ansled inferiorlv

. J height & sup. length . { height . I length superiorly . I height of lat. plate . I inf. length . broadly separated . ¿ width of fronto-ethmoid . t height of frontal . plates broadly separated attachment ethmoid attachment by cribriform plate . J separation inferiorly . I separation superiorly . relativelv broad suoeriorlv . relatively narrow post. . t lat. cribriform plate . I width post. (spheno- . I lat. cribriform plate . I anterior width . I width post. (spheno- ethmoid synchondrosis) length . I length of plate ethmoid synchondrosis) . I width post. (spheno- . pl¿te depressed ethmoid svnchondrosis) . nofTnal . normal . majority normal . I height of medial plate . foramen caecum ant. (previous surgery)

. t length . relatively normal . I length . I tength . splayed posteriorly . prominent (L) anterior . splayed more inferiorly and . splayed more inferiorly clinoid posteriorly and posteriorlv . splayed anteriorly & . normal . normal size . normal size medially . splayed posteriorly & . splayed posteriorly & laterallv I aterally

Chnpter 3 Page 385 Table 3.3 BONE & Patient RN Patient SH Patient JS Patient IP REGION SPHEN0ID cont. . Greater Wing . I length spheno- . J sup. orbital . I lat. splay of bones . I length spheno- zygomatic suture fissure zygomatic suture . I sphenofrontal . I sup.orbital fissure suture . sphenofrontal suture . I lat. splay of normal or I bones . t lat. splay of bones . . Body constricted . 1 post. clinoid . constricted orbital . I length body superiorly orbital apex width apex & inferiorly . hyperplastic . ant. clinoid | (R) . I widths anteriorly . t spheno-occipital base . hypoplastic base . I spheno-occipital synchondrosis (lat.) synchondrosis (sup.) . I ant. heighr . ,l angles of body . t spheno-ethmoid splay from midline (ie. synchondrosis narrowed) . I width slightly TEMPORAL . Squamous abnormal . normal . incompletely recorded . incompletely recorded temporal bone . Ext. auditory . shape distortion . shape distortion . normal . severe shape distortion meatus (f post. Iat. (f post. Iat. distance) distance) Zygomatic . I length . J length .flength.fheight . I length process .1 heieht . angled late¡ally . ansled laterallv . . Petrous normal I spheno-petrous . J jugular foramen (R) . I jugular foramen temporal temporal suture . I occipital mastoid . t occipital mastoid suture suture . I petrous ridge lengths . I petrous ridge length . 1 widths of bones . splay of bones more . I splay of bones post. & narrowed pos terior

PARIETAL . not recorded . not recorded . not recorded . not recorded OCCIPITAL . Calvarial . not ¡ecorded . not recorded . not recorded . not recorded . . Cranial base minor deformity . normal . J jugular foramen (R) . J jugular foramen . foramen magnum . I temporo-occipital suture shape asymmetric (inf.) . foramen magnum shape asymmetric CRANIAL BASE SUTURES . Anterior Fossa . 1 frontal ethmoid . normal . I frontal ethmoid . I spheno-ethmoid . { spheno-frontal attachment synchondrosis . I spheno- .j spheno-frontal (orbital) zygomatic suture (R) . I spheno-zygo suture Middle Fossa normal .I spheno-petrous . t spheno-squamous . I spheno-squamous temporal suture temporal suture (L) temporal suture (L) (sup.)

Posterior normal . I temporo- . I temporo-occipital . I temporo-occipital suture Fossa occipital suture suture (sup.) (R) (inf .) (sup.) .J sup. spheno- . f occipital mastoid suture .f inf. spheno- occipital . t spheno-occipital occipital synchondrosis synchondrosis (lat.) synchondrosis CRANIOFACIAL DIMENSIONS and ANGLES . Facial Heights . not measurable . not measurable . not measurable . not measurable . Facial Angles SNA . borderline I . normal . normal . decreased SNB . not measurable . not measurable . not measurable . not measurable . C-Base Angle . normal . acute . normal . obtuse . C-Base . normal . normal . normal . I length Dimensions

Page 386 Crouzon Synclrome Table 3.3 continued:- Patient LW Patient AY Patient HC Patient TS

..t spheno-zygomatic suture . rel normal distances . I spheno-zygomatic sutu¡e . I spheno-zygomatic .l sup.orbital fissure . borderline I sup. orbital . I lat. splay of bones suture . sphenofrontal (orbital) fissure . I petrous temporal suture . ¡ width of greater wing (L) suture normal .f lat. splay of bones (sup. L) . . t lat. splay of bones I lat. splay of bones . I spheno-petrous . narrowed posteriorly . t petrous temporal suture .I spheno-petrous temporal temporal. suture (inf. R) (sup. L) suture (suo.) (sup. L) . I body length . I body length . body length normal . t body length . t spheno-occipital . I spheno-occipital . I spheno-ethmoid . I ant. length synchondrosis (lat.) synchondrosis (lat.) synchondrosis . (sella enlarged) . orbital apex ant. . I spheno-ethmoid . sella I in size .f spheno-occipital . I spheno-ethmoid synchondrosis .f spheno-occipital synchondrosis (sup.) synchondrosis . b¡oad anteriorly synchondrosis (sup. & inf.) . broad anteriorly . broad anteriorly . sella I in size (narrow posteriorly) . J height anteriorly (R) . t spheno-occipital svnchondrosis (inf.)

. incompletely recorded . incompletely recorded . incompletely recorded . incompletely recorded . Drominent mastoid . prominent mastoid . slight shape distortion . shape distortion . atretic EAM (L) . shape disto¡tion . (l sup.ant. disiance (R)) . (1 sup.ant. distance) . shape distortion (R) . (l inf, distances) . (I sup. ant. distance) . I length . relatively normal . I length (L) . relatively normal . minimal asvmmetrv . angled medially . I jugular foramen (R) . borderline J jugular . borderline I jugular foramen . jugular foramen distorted . I spheno-petrous foramen .I spheno-petrous temporal . t spheno-petrous temporal suture (sup.) (R) . I spheno-petrous suture (sup.) (R) temporal suture (sup.) (R) . t occipital mastoid suture temporal suture (sup.) (L) . I occip. mastoid suture (L) . 1 occipital mastoid suture . I temporo-occipital suture . I occipital mastoid suture . I temporo-occipital suture (L) (inf.) (L) . I temporo-occipital (inf.) (L) . I length petrous ridge . t length petrous ridge suture (inf.) (L) . petrous ridge normal length . I distance between . I length petrous ridge temporal bones . I distance between EAM . not recorded . not recorded . not recorded . not recorded

. not recorded . not recorded . not recorded . not recorded . I jugular foramen (R) . I jugular foramen . I jugular foramen (L) . jugular fo¡amen distorted . I temporo-occipital suture . 1 temporo-occipital . I temporo-occipital suture . sutures & synchondroses (inf.) (L) suture (inf.) (L) (inf.) (L) normal . I spheno-occipital . t spheno-occipital . except I spheno-occipital synchondrosis (inf.) synchondrosis (inf.) synchondrosis (sup.)

. I spheno-ethmoid . t spheno-ethmoid . I spheno-ethmoid . t spheno-frontal (ant. synchondrosis synchondrosi s synchondrosis fossa) suture (R) . t spheno-frontal (ant. .f spheno-frontal (ant .{ spheno-frontal (orbital) . I spheno-frontal (orbital) fossa) suture fossa) suture suture (R) suture (L) .l spheno-zygomatic suture . I soheno-zvsomatic suture . I spþeno-zygo suture . I spheno-petrous . I spheno-petrous .f spheno-petrous tcmporal . I spheno-petrous temporal suture (sup.) (R) temporal suture (sup.) (L) suture (sup.) (R) temporal suture (sup.) (R) o I spheno-petrous temporal suture (inf.) (R) . I temporo-occipital suture . I ternporo-occipital . I temporo-occipital suture . I occipital mastoid suture (inf .) suture (sup., inf. & L) (inf.) (L) .J spheno-occipital . f occipital mastoid sutu¡e . I occipital mastoid suture . occipital mastoid suture synchondrosis (sup.) . I spheno-occipital (R) normal synchondrosis (lat.) . I spheno-occipital .f spheno-occipital synchondrosis (inf. & lat.) synchondrosis (inf. & sup.)

. not measurable . not measurablc . increased . increased

. normal . decreased . decreased . decreased . normal . not measurable . decreased . decrea^sed . acute . borderline acute . obtuse . obtuse normal . normal . normal . normal

Chapter 3 Page 387 Page 388 Crouzon Sywlrome 3.5 Quantitative Analysis by Anatomical Unit in the Eight Patients with Crouzon Syndrome

3.5.1 The Morphology of the Mandible in the Eight Patients with Crouzon Syndrome

Distances: The majority of the distances measured from the 3D CT reconstructions of the mandibles in this group of patients with Crouzon syndrome were not significantly different from the experimental standard although many of the measurements were above the mean suggesting a tendency towards enlargement of this bone. Of the total number of 128 distances measured (16 measurements per patient), 13 were significantly increased and 7 were decreased compared *itt tt" appropriate age-matched control. Many abnormal measurements resulted from an anterior position of first molar suggesting crowding of the dentition.

Dimensions and Angles: The majority of the dimensions of the mandible were not significantly different but a similar trend towards larger mandibles was again suggested by the majority of measurements being greater than the mean. There was no consistent increase or decrease in the widths of the mandible. Ramus dimensions were generally larger than the mean. The anterior mandibularheightat the symphysis was significantly greater in the 4 older patients. This may reflect either a compensatory overgrowth, to obtain a functional occlusion, or a primary growth abnormality. The gonial angle was increased in 3 patients. The angles based around the coronoid base and first molar showed the widest positive and negative significant Z scores.

This was in part due to the variable anterior position during growth of the molar in the patients.

In general, the width of the mandible at the level of the gonial angles was decreased, with a reduced anterior mandibular angle, except in the oldest patient (Patient TS) in which these dimensions and angles were increased. Clinically, this patient had very broad and coarse features associated with a frontal gibbosity and flaring of the mandibular angles, not seen in the other patients. The distances between the condyles in all patients were not significantly different from the experimental standard or reduced, except in the patient with the most markeci clinicai deformity (Patient IP), where this measurement was increased. The significant distortion of the temporal bone in this patient would appear to make the greatest contribution to the condylar

Chapter 3 Page 389 position. These 2 patients may represent different subtypes of Crouzon syndrome. In the majority of patients, there was a tendency towards a minimally longer and more slender mandible, with an increased gonial angle and compensatory symphyseal growth. The changes became more apparent in the older patients.

Discussion: Major growth disturbance of the mandible does not typically occur in Crouzon syndrome. Minor abnormalities of shape and position along with either prognathism or retrognathism have been described in case reports, and in greater detail in quantitative studies

(Kreiborg, 1981 ; Costaras-Volarich and Pruzansky, 1984).

Kreiborg's cephalometric measurements of the mandible revealed three main findings in patients with Crouzon syndrome. Firstly, the gonial angle was slightly greater than in the controls but still within the normal range. This finding was confirmed in the patients studied here, using slightly different definitions of the landmarks, where the measurements were often found to be statistically increased. Kreiborg also found that the mandibular length and height were significantly smaller than controls in the female Crouzon population, but normal in the male population. The sample of patients studied here was too small to determine any differences with respect to sex. Both mandibular length and height were within, and evenly spread across the normal range. The significant findings were one patient with a short left ramus and another with a long left body. Despite a slightþ more obtuse gonial angle, the total mandibula¡ length was not increased.

In a cephalometric analysis of 30 Crouzon syndrome patients, Costaras-Volarich and

Pruzansky (1984) found that the mandibular body length was significantly shorrer and the mandibularramus tended to be long but not statistically so. They described the ratio of ramus heighttobody length approaching 1:1, compared with 2:3 in the normal population. The total mandibular length was not significantly different from the experimental standard but tended to be short. This finding was not confirmed in this study.

Kreiborg also found that the mandible was retrognathic in relation to the cranial base. This relationship was not investigated in this study. It is possible that a posterior position of the mandible contributes to a narrow upper airway in many cases.

Page 390 Crouzon Syndrome It is clear the mandible undergoes subtle changes in patients with Crouzon syndrome. Based on this study,3 patterns of mandible were identified (Figure 3.35).

1. Primary Crouzon Mandible (Patients RN, SH, HC, JS, LW and A)): This is the commonest form of mandible and is represented by the majority of studies which show a slightly increased gonial angle, and tendency to increased symphyseal height. The ramal and body lengths are usually not significantly different from the experimental standard. The gonial angle increase may be a primary growth abnormality or related to the cranial base and soft tissue attachments. The symphyseal height may be compensatory for the increased angle and deficient maxilla.

2. Secondary Crouzon Mandible (Patient IP): This mandible is distorted due to cranialbase deformity directly affecting the position of the mandibular condyles. This presents with a broad condyle and ramus and increased intercondylar distances.

3. Gibbous Mandible (Patient TS): This deformity is due to a localised overgrowth of bone in the region of the mandibular angle and may be associated with a frontal gibbosity and bony overgrowth in other areas.

3.5.2 The Morphology of the Maxilla in the Eight Patients with Crouzon Syndrome

Distances: The measurements of the distances between the landmarks of the maxilla extended above and below the normal range, with such variability as to make it difficult to find any recurrent patterns. This is somewhat surprising as a hypoplastic maxilla is one of the major features of Crouzon syndrome and some uniformity of the distances might be expected. The size and shape of the maxilla is also influenced by the secondary deforming forces of the cranial base and the surrounding bony structures such as the zygomatic, frontal and nasal bones.

Variable distortions of growth in these regions contributes to the variable pattern of deformity of the maxilla.

Dimensions and Angles: The majority of dimensions were either enlarged or not significantly different from the experimental standard. An increase in vertical height was found at the

Chapter 3 Page 391 expense of anterior growth. The height and width of the maxilla were generally greater than for

the experimental standard, while measurements in the anterior-posterior direction were reduced.

Discussion: The maxilla in Crouzon syndrome is clinically described as hypoplastic. This refers

to the flat appearance of the midface and is due to the reduced anterior growth of the maxilla.

This is most commonly evident during late childhood and early adolescence when maxillary

growth is maximal. The infants,2 year old children and 6 year old children would therefore be

expected to have most variables within the normal range. In this study the infants showed

minimal deformity of the maxilla, as did one of the} year old children (Patient JS). The other 2 year old child, Patient IP, showed marked involvement which correlated with the severe clinical deformity. The 6 year old children also showed marked measurement abnormalities. The 2 adult patients would be expected to show predominantly hypoplasia of the mandible. The adult patients demonstrated some reduced anterior distances with increased lateral and posterior distances. The pattern was one of a broad and tall posterior maxilla with a small anterior maxilla.

The relationship with the cranial base was not examined in this study and would have provided additional information about the posterior maxilla. In Kreiborg's study (1981), the maxilla was found to be retrognathic and inclined upwards and backwards and the lateral and Ap widths were reduced, as well as the height.

Many posterior measurements in cephalometric analysis of the maxilla rely on points not found on the bone itself, such as the sella and the apex of the pterygomaxillary fissure. This latter point commonly belongs to the junction of greater wing of the sphenoid with the pterygoid. The true highest point of the maxilla in the deformed skull of Crouzon syndrome is more medial and often higher than can be identified on cephalograms. The landmark can be readily be seen on the CT coronal slices. This problem may account for the reduced posterior dimensions of the maxilla described by Kreiborg, conflicting with the data in this study. On the other hand, it enables Kreiborg to make valid statements about the relationship of the position of the maxilla to the cranial base. The broad and high posterior maxilla described in this study, often with normal or increased dimensions, is clearly related to the development of the ethmoid and cranial base and will be discussed in the relevant sections.

Page 392 Crouzon Syndrome Growth of the palatal sutures in the normal maxilla have been shown to occur up until adolescence (Persson, 1973). Kreiborg found the maxilla of Crouzon syndrome was smaller in all the dimensions measured and he related this to premature synostosis of the maxillary sutures. Previous studies (Kreiborg and Bjork, 1982) on a dried skull with Crouzon syndrome showed premature synostosis of the transverse and mid palatal sutures and of the vertical squamous sutures between the palatine bones. Early synostosis was also seen at the fronto- maxillary and zygo-maxillary sutures. In this study, increased suture length suggesting premature fusion was found at the fronto-maxillary, naso-maxillary and zygo-maxillary sutures. No common pattern was found implying that sutures were involved with variable severity.

Eight patients in Kreiborg's series had merallic implants inserted to allow assessment of maxillary sutural growth. Premature sutural arrest was found in 7 of these cases, occurring as early as 2 yearc of age in 1 patient (1 - 12 years in remaining patients). Lack of anterior growth with an overall decrease of downward growth was characteristic. Remodelling of the maxilla as a result of this process was observed but was not assessed statistically. Characteristics described by Kreiborg included: decreased bone apposition at the maxillary tuberosity, increased bone apposition at the maxillary spine, resorptive lowering of the posterior nasal floor and excessive alveolar height. The orbital surface of the maxilla revealed signs of bone resorption and the relative width of the dental arch decreased with growth. In this study, increased anterior alveolar height (pr-ans) was found in 1 adult with a tendency to be increased in the other. The maxillary dental arch width (gpfl-gpfr, ecsl-ecsr) was normal, although the anterior maxillary angles (gpfl-ans-gpfr, gpfl-pr-gpfr) were increased in 3 patients (including the 2 adults) and decreased in 2 patients.

It is suggested, based on data from this study, that the maxilla in patients with Crouzon syndrome has 3 predominant features (Figure 3.36) although a larger number of patients are needed to confirm this.

1 . Increased maxillary height

2. Increased maxillary width

Chapter 3 Page 393 3 . Reduced anterior-posterior distances and dimensions.

This deformity was measurable in the adult patients, children at 6 years of age and in a severely

affected child aged 2.The maxilla was found to be extending up into the inter-orbital region at

its junction with the ethmoid resulting in an increased height posteriorly. Increase in inter- orbital distances also makes the maxilla broad at its superior margin. In addition, the increased intra-orbital component of the maxilla contributes to the proptosis and hypertelorism. This leaves a reduced volume of sub-orbital maxilla, a feature which is seen clinically and encountered at surgery. The majority of the sub-orbital height of the maxilla is made up of alveolar bone, with a close relationship of the palate to the cranial base.

3.5.3 The Morphology of the Nasal Bones in the Eight Patients with Crouzon Syndrome

Distances. Dimensions and Angles: The measurements of the nasal bones in this group of patients with Crouzon syndrome demonstrated increases in the lengths of the naso-maxillary sutures, suggesting some prominence to the lateral part of the nasal bones (Figure 3.36). In many patients, the bones were broad inferiorly and also splayed laterally and inferiorly. In several patients the projection of the nasal bones was also reduced (Patients IP and TS). The only patient with a normal or decreased maxillary suture length with a prominent nasal angle had a correspondingly normal clinical appearance to the nose (Patient LW, Figure 3.5).

Discussion: The typical feature of the nasal structures in Crouzon syndrome is the so-called

"parrot beak" deformity. This is characterised by a lack of cartilaginous projection for the nose.

This produces a retruded tip with overhang, giving a beaked appearance to the structure.

Clearly the nasal deformity in Crouzon syndrome is a component of both nasal bone structure as well as cartilaginous support. The nasal bone deformity has been described above and usually shows some downward and lateral growth characteristics. The growth of the septal cartilage is directed by the medial plate of the ethmoid and the vomer. In this study, these structures were relatively normal but showed a tendency for downward angulation, particularly in the older patients (Patients AY, HC and TS). It is interesting to note that the patient with the more norrnal nasal bones and in particular, the prominent nasal angle (s-n-na) had a conespondingly more normal appearance and therefore presumably a more normal cartilaginous

Page 394 Crouzon Syndrome framework support @atient LW). The position of the nasal tip is also influenced by the lack of anterior projection of the maxilla. The relationship of the fronto-nasal and naso-maxillary sutures may alter the role of the nasal bones in determining the extent of parrot beaking but this cannot be definitely concluded from this study. In summary, the nasal deformity is related to the length and prominence of the nasal bones, the size and angle of projection of the medial ethmoid plate and vomer, and the amount of anterior growth of the maxilla. The variation in appearance of the nose may be attributed to the severity of involvement in each bony region, and of the sutures between these structures.

3.5.4 The Morphology of he Frontal Bone in the Eight Patients with Crouzon Syndrome

Distances: For the purposes of this study, the frontal bone was analysed as 4 separate regions: the frontal bone; the calvarial component, which contributes to the atypical head shape; the supra-orbital region, which typically provides inadequate superior cover for the globes in these patients; the junction with the ethmoid bone medially and the junction with the sphenoid bone posterioriy and laterally. Deformity of this bone is part of the classical presentation of Crouzon syndrome and its analysis is particularly important.

Calvarial Region: Premature fusion precluded identification of the sutures and as a result the calvarial distances and dimensions were not measured. The range of clinical calvarial abnormalities found in this study is presented in Chapter 2 and the deformity in each patient is presented with the qualitative data in Chapter 3. Fusion of the calvarial sutures influences the shape and position of surrounding structures such as the supero-lateral orbital rim of the frontal bone, the zygomatic bone, the temporal bone and the sphenoid greater wing. While this region is important in the overall deformity this study has focussed on the cranial base and facial bones.

Supra-orbital Region: All patients exhibited some shape distortion of the supra-orbital region.

The typical finding was a more rectangular shape to the superior orbital rim. Either the superior orbital point or the supero-lateral orbital point was more laterally placed and accounted for this deformity. (The angle of the superior orbital rim was not measured and may have provided greater information on the discrepancy in this region). The deformity of the supra-orbital region

Chapter 3 Page 395 was mild in some cases but was very severe in others where the lateral wall was greatþ swept

up and the height of the lateral orbital wall was increased (Patients RN and Ip). This deformity

was found in conjunction with the spheno-zygomatic pattern of the zygomatic bone (Section

3.5.5 Zygomatic Bone). A moderate deformity was also seen in Patient HC. Increased width

across the frontal supra-orbital ridge was recorded in the older and severely involved patients

(Patients IP, RN, AY, HC, TS) and was related to pathology of both the medial and lateral

orbital walls (Figure 3.37) and corresponded with the predominant pattern of deformity of the maxilla.

Ethmoid Attachment: The frontal ethmoid attachment was represented by the lateral part of the

cribriform plate and the supero-medial part of the orbit. Tluee patterns were identified:

1 Lengthening of the frontal ethmoid attachment with a corresponding constriction

in dimensions at the orbital apex (Patients RN, JS, LW and HC).

2. Normal frontal ethmoid attachment (Patients SH and AY)

J Reduced frontal ethmoid attachment length with a broad anterior attachment

(Patients IP and TS).

The increase in the frontal ethmoid attachment length appeared to be related to the increased dimensions of thecribriform plate. The overall ciinical deformity in the patients with a normal ethmoid junction was less severe. A greater degree of significant pathology in the region of sphenoid bone was found in those patients with reduction in the length of frontal ethmoid attachment (Section 3.5.8 Sphenoid bone).

Sphenoid Attachment The principal finding in the majority of patients was a reduction in the lengthof the superiororbital fissure. This usually occurred in those patients with an increased frontal ethmoid attachment length. Those with a reduced frontal ethmoid attachment length had significant increase or tendency to be increased in the superior orbital fissure length (Patients Ip and TS).

Discussion: Fusion of the frontal and parietal sutures with extensions into the zygomatic bone have been previously demonstrated (Kreiborg and Bjork, 1982). The concept of a coronal ring

Page 396 Crouzon Syndrome of sutures extending into the cranial base was suggested by Burdi et al. (1986). In this study several patterns of deformity of the supra-orbital, ethmoid and sphenoid sections of the frontal bone emerged from the measurements. It was unfortunate this could not be conelated with measurements of the calvarial deformity. The involvement of frontal and zygomatic bones altered the superior orbital rim laterally and produced a more rectangular appearance. Medially and posteriorly, along the junction of the ethmoid and sphenoid bones, a range of deformity was seen. Lengthening of the ethmoid attachment and shortening of the superior orbital fissure was identified in one group of patients. A normal or less severe type of this deformity was seen in another, smaller group. In the third group, shortening of the ethmoid attachment with lengthening of the superior orbital fissure was found. The pattern of the medial deformity here did not appear to be related to the clinical or measured deformities in the region of the facial skeleton, but appeared to be more a product of the cranial base pathology. As with the calvarial pathology, it may be that the type of deformity is determined by which region of sutures is involved and to what extent. Due to the complex nature of the frontal bone, posterior deformities (that is, in the region of the sphenoid bone) may influence the position of other anterior structures. The effects of intracranial pressure, which are noted to be significant in the region of the sella (Kreiborg et a1.,1993),may also exert deforming forces on the ethmoid, the wings of the sphenoids and the frontal bone directly.

3.5.5 The Morphology of the Zygomatic Bone in the Eight Patients with Crouzon Syndrome

Distances: The distances measured in this region are very informative as they are made up of a large number of sutures and reflect the position of the lateral orbital wall and the prominence of the cheek. Two dominant patterns emerged, depending upon whether the spheno-zygomatic suture or tl're fronto-zygomatic suture was involved. Four patients (Patients RN, IP, HC and

TS) had increased distances at the spheno-zygomatic suture. These patients included the children with the more severe disease and the 2 adults with the established deformity, ail with greater clinical deformity around the orbit. The other group (Patients SH, LW and AY) had increased distances at the fronto-zygomatic suture and normal or decreased distances at the spheno-zygomatic suture. These sutural measurements were normal in one patient (Patient JS) with correspondingly normal zygomatic bone measurements and dimensions. Only 2

Chapter 3 Page 397 measurements were increased in this patient, one related to the height of the lateral orbital wall and the other associated with the zygo-maxillary suture on one side.

Dimensions: The dimensions reflected, to some extent, the abnormal suture patterns. The spheno-zygomatic group tended to have increased zygomatic height and decreased length. The fronto-zygomatic group tended to have normal overall dimensions. This may have been predicted given their young age and lack of severity.

Discussion: The patterns of deformity of the zygomatic bone (Figure 3.38) were, in order of severity:

I . Minimal change (Patient JS)

2. Fronto-zygomatic suture pattern (Patients SH, LIV and AY)

3 . Spheno-zygomatic suture pattern (Patients RN,IP, HC and TS)

The morphology of the zygomatic bone demonstrates very well the role of adjoining bones and the interplay of the sutures in determining the size and shape of the bone. A strong association between suture dimension and bone shape was shown. The sutures with the sphenoid and frontal bones appeared to be more relevant than the sutures with the maxilla or temporal bone as variable involvement of the zygo-maxillary suture and zygomatico-temporal suture (Section

3.5.9 Temporal Bone) was present.

3.5.6 The Morphology of the Vomer in the Eight Patients with Crouzon Syndrome

Distances: All distances were not significantly different from the experimental standard in the younger children. In the adult patients the vomer tended to be smaller than the experimental standard

Dimensions and Angles: The angle of the vomer relative to the cranial base was significantly increased in the severely affected and olcler patients (Patients IP, HC, TS). This may be partly a result of the influence of the cranial base deformity on the angle however, the inferiorly angled

Page 398 Crouzon Syndrome vomer strongly suggests the lack of forward growth in favour of downward growth (Figure 3.39).

Discussion: Studies have suggested that the lack of midface growth is due to a lack of nasal septal drive (Enlow , I97 5). V/hile it is difficult to determine if the disturbed vomerine growth is a primary or secondary event, it would appear to make up an important contribution to the characteristics of the Crouzon midface. The increasingly significant results with increasing age suggest a primary developmental problem in view of the timing of midface growth and the importance of nasal septal development in maxillary development.

3.5.7 The Morphology of the Ethmoid Bone in the Eight Patients with Crouzon S-yndrome

Deformity of the ethmoid bone in Crouzon syndrome has classically been described as broad with depression of the cribriform plate (Bertelsen, 1958). As the name suggests (ethmoid:

Greek ethmos sieve; sievelike), most attention has been focused on the cribriform plate. This study has examined other areas and divided the ethmoid into the lateral plate, the cribriform plate and the medial plate and examined the relationships with the surrounding bones.

Lateral Ethmoid Plate: The lateral plate comprises the medial wall of the orbit. A typical finding was a reduction in the size of the plate, in particular the height. The separation of the two lateral plates was variable, with the overall tendency to be broadly separated. A wedge shape to the ethmoid was found when the lateral plates were separated broadly anteriorly, but were more narrowly separated posteriorly (Patients RN, SH, JS, TS).

Cribriform Plate: In the majority of cases the cribriform plate was increased in its dimensions with respect to length and width. An increase in the posterior width represents lengthening of the spheno-ethmoid synchondrosis and was found in 4 patients (Patients IP, LW, AY, HC).

These patients did not sl'row the wedge shape to the ethmoid bone. The frontal ethmoid attachment was discussed with the frontal bone (Section 3.5.4).

Medial Ethmoid Plate: The medial plate was normal in the infant and 6 year old age groups and in one adult (Patient HC). In the 2 year old patients and the adult patient TS, increased dimensions of the medial plate was seen.In the oldest patient (TS), the height of the plate was

Chctpter 3 Page 399 increased and corresponded to an increase in the vertical dimensions of the medial plate of the

ethmoid and the vomer, with a relative lack of AP growth.

Discussion: The findings of the ethmoid bone are consistent with what is known about this

structure from previous studies (Bertelsen, 1958; Kreiborg, 1981). The ethmoid bones were broad and contributed to the hypertelorism and the reduction in orbital volume and had a secondary effect of increasing the overall breadth of the face (Figure 3.40). Along with the sphenoid and frontal bones, this bone directs the growth of the roof and lateral wall of the orbit and, along with the maxilla, influences the shape and angle of the floor. Involvement of the spheno-ethmoid synchondrosis has been suggested by other authors (Burdi et al., 1986). This study was able to confirm this in some but not all patients. In those patients without lengthening of the spheno-ethmoid synchondrosis a wedge shaped ethmoid bone was found.

The medial orbital wall was generally reduced in its height and length but with some minor discrepancies in terms of which regions were shortened (that is, anterior-posterior, superior- inferior). The medial plate was less severely involved. The depression of the cribriform plate was not measured along the lines of Bertelsen and Kreiborg. Additional angles representing the splay of the plate and separation from the midline were identified in this study and confirmed the broad and lateral position of the ethmoid. The reduced dimensions of the lateral plate contributed to create the impression of the ethmoid being depressed and protruding into the medial wall of the orbit. The reduced lateral plate size was associated with the increased inter- orbital component of the maxilla. Hence the maxilla may have a greater role in the development of reduced orbital volume and proptosis.

In the case of the ethmoid bone, pathology is related to the sutural and synchondrosis abnormalities between the frontal, sphenoid and ethmoid bones along with deforming bony and soft tissue forces such as increased intracranial pressure.

Patterns of deformity of the ethmoid bone in this study are summarised as

1 Lateral plate

. normal (Patients RN, SH)

. reduced size (Patients JS,IP, LW, AY, HC, TS)

Page 400 Crouzon Syndrome 2. Posterior ethmoid

. spheno-ethmoid synchondrosis lengthened (Patients IP, LW, Ay, HC)

. wedge shaped bone (Patients RN, SH, JS, TS)

3. Frontal ethmoid attachment (Section 3.5.4 Frontal bone)

4 Cribriform plate

. not depressed relative to anterior cranial base (all patients)

5 Medial plate

. normal (Patients RN, SH, LU/, AY, HC)

. increased size (Patients JS,IP, TS)

3.5.8 The Morphology of the Sphenoid in the Eight Patients with Crouzon Syndrome

The sphenoid is the most intricate and complex bone of the cranial skeleton. The name is derived from the Greek for "wedge". This may be due to its shape, but also to its position between the other craniofacial bones. Via its elaborate processes, the sphenoid articulates with or is in contact with 9 other craniofacial bones. The measurement and determination of its shape is correspondingly complex. In this study the anatomy of the sphenoid bone was subdivided into four regions; the Lesser Wing, the Pterygoid Plate, the Greater Wing and the Sphenoid

Body. These regions may present with different patterns of distortion. The summary of major trends is listed.

Lesser V/in& The lesser wing measurements varied (Figure 3.41).The moderate deformity was represented by prominent anterior clinoid processes and relatively normal size of the lesser wing. The more severe deformity showed a reduction in the anterior ciinoid presumed due to bone resorption in the region of the sella. The lesser wing was longer and was associated with sweeping up of the lesser wing. This resulted in greater lateral protrusion of the bone contributing to a broad head shape.

Summarv of Deformitv:

I . Moderate Deformity (Patients RN, SH, JS, LW and Ay)

Clnpter 3 Page 401 Prominent anterior clinoid

Normal or reduced length of lesser wing

Angles variable

2 Severe Deformity (Patients IP, HC and TS)

Small anterior clinoid

Increased length lesser wing

Increased distance between tips of wings

Angles variable

Pter)¡goid Plate: The size (distances and dimensions) of the pterygoid plate was generally not

significantly different fro,m the experimental standard. The angle of the pterygoid plate from the

sella-nasion line was increased in the most severe clinical presentation (Patient IP) and the adult patients (Patients HC and TS) (Figure 3.42). A lateral and posterior position of the pterygoid axis in these patients reduced the anterior position of the maxilla, and accounted for the greater severity of facial deformity in these patients. Muscle development in this region may subsequently be affected and produce deforming forces on other structures such as the mandibular ramus and gonial angle (Section 3.5.1 Mandible).

Summary of Deformi[t

1 No deformity (Patients RN, SH, JS, LW and Ay)

Normal dimensions and normal axis

2. Deformity (Patients IP, HC and TS)

Normal dimensions

Increased angle of pterygoid axis (lateral and posterior)

'Wing: Greater The sphenoid greater wing was splayed more laterally than in the control population (Figure 3.42).The curve of protrusion into the orbit was not measured specifically.

The lateral protrusion may be accounted for by the effect of surrounding squamous suture fusion preventing forward growth. Additionally, lateral growth of the ethmoid bone may push the orbit and subsequently the greater wing laterally. Fusion of the spheno-temporal suture may

Page 402 Crouzon Syndrome also contribute to holding back the greater wing. As has already been discussed, the

surrounding suture lengths were variably involved , atypical feature of Crouzon syndrome.

Summary of Deformitv:

1 Spheno-zygomatic suture involvement (Patients RN,IP, HC and TS - the more

severe cases)

2 . Distortion of orbital component of greater wing (Patient IP)

3 . Increased lateral protrusion of greater wing (A11 Patients)

4 Spheno-temporal suture involvement (5 older Patients) (Section 3.5.I2 Cranial

base sutures)

Sphenoid Body: The dimensions of the sella \¡/ere generally increased as a result of increased bone resorption (Figure3.43). The spheno-occipital synchondrosis showed 2 patterns. Firstly an increase in lateral height and normal width and secondly, a normal lateral height and reduced width. The measured deformrty of the spheno-occipital synchondrosis makes its shape consistent, but size variable. The impact of this shape on the growth of the synchondrosis is not clear, but a reduced or distorted pattern of growth could result. Qualitative examination shows the spheno-occipital synchondrosis to be patent radiographically in the 6 children in this study.

The synchondrosis was not visible in the 3D CT reconstruction of any except the 2 youngest patients.'What is happening at a cellular level in the cartilage is the most pertinent question, but cannot be answered from this study.

Summary of Deformity:

1 . Lateral body tended to be larger (All Patients)

2. Lateral spheno-occipital synchondrosis lengthened (Patients IP, L'W and AY)

a J Spheno-occipital synchondrosis (superior, inferior) normal or reduced in length

(All Patients)

Chapter 3 Page 403 Discussion: The features of the sphenoid in Crouzon syndrome have been described in the

literature from dried specimens and cephalometric examination. Findings have included

sweeping up of the lesser wing, increased protrusion of the greater wing into the orbit,

enlargement of the sella turcica and variation in the cranial base angle (a feature not solely

determined by the sphenoid bone) (Kreiborg, 1981; Kreiborg et al., 1993). Sutural

involvement of the spheno-zygomatic, spheno-temporal (calvarial) sutures has also been

described (Kreiborg and Bjork, 1982). The spheno-occipital synchondrosis has been shown to not be visualised on 3D CT reconstructions (Kreiborg et al., 1993).

In this study, several features of the natural history of Crouzon syndrome have emerged which are typified by the sphenoid bone (Figures 3.41 - 3.43). The sphenoid bone may be involved in

4 ways. Firstly, the primary growth of the sphenoid may be abnormal. Secondly, the sutures and synchondroses of the sphenoid may influence its subsequent growth. Thirdly, the sutures of other bones and regions may exert distorting influences on the sphenoid. Finally, the pressure effects of the brain will influence the extent of bony apposition and resorption, particularly in the region of the cranial base. Consequently, a range of deformity is seen, with the features being more marked in older patients and those with the more severe disease.

Measurement of the distances, dimensions and angles cannot necessarily separate these influences but demonstrate the result of these forces.

The following list comprises the major findings of the sphenoid bone in this study

I . The spheno-ethmoid synchondrosis is often abnormal

2. Lengthening of the lesser wings

3 . Laterai protrusion of the greater wings

4. Variable involvement of the spheno-zygomatic suture and spheno-temporal

sutures

5 . Tendency for increased size of sella

6 Variable involvement anteriorly at the junction of the sphenoid, frontal and

ethmoid bones.

Page 404 Crouzon Synclrome 3.5.9 The Morphology of the Temporal Bone in the Eight Patients with Crouzon Syndrome

Temporal Squamous Bone: The temporal squamous bone was only fully measurable in the infants where the landmarks asterion (as) and sphenion (spt) were visible. Premature fusion of sutures and,/or reduced visibility of the sutures made the analysis of the superior part of the squamous temporal bone impossible in the other patients. Of the distances that could be measured the distance from the stylomastoid foramen to the mastoid process tip (ma-smf) was increased in 3 of the older 4 patients suggesting increased prominence of this process.

External Auditory Meatus: The external auditory meatus measurements were symmetrical in nearly all patients. Increased distances were usually adjacent to decreased distances, implying a distortion or tilting of the external auditory meatus. In summary, the external auditory meatus measurements showed increased distances in 4 patients (Patients RN, SH, IP and AY), equal increased and decreased distances in 2 patients (Patients JS and LW) and reduced distances in 2 patients (Patients HC and TS). One patient (Patient HC) had atresia of the external auditory meatus and an associated abnormality of the adjacent petrous temporal bone.

Zygomatic Process: The zygomatic process was also symmetrical. The zygomatic arch distance

(auI-ztI, aur-ztr) was reduced in the majority of patients and the height of the articular fossa was increased in some patients.

Petrous Temporal Bone: Analysis of the petrous temporal bone revealed that the petrous temporal ridge distance (petar-petpr) was increased in the majority of patients. Suture lengths at the apex of the bone (fis-peta, peta-jfp) varied greatly (Figure 3.44). Distances of the jugular foramen were reduced, to a greater degree on the right side (Figure 3.45). The occipital component of the jugular foramen (fl-jfp, jfp-jfm) showed a similar trend in the majority of patients. The petrous temporal-occipital suture was reduced on the left with non-significant reduction on the right. Increased distances from the mastoid to jugular foramen were found and rnay reflect the prominence of the mastoid process in the population as well as the narrowing of the jugular foramen.

Chapter 3 Page 405 Dimensions: The dimensions between the temporal bone were slightly increased, with the

exception of Patient HC who had left external auditory canal atresia, and showed reduced

distances between the left and right bones, as well as reduced angles. Several other patients

showed an increased distance between the internal auditory meati points, the porion points and

the jugular foramina. The angles of the petrous temporal bone were normal in 5 patients

(Patients SH,IP, LW, AY and TS).

Discussion: The temporal bone in patients with Crouzon syndrome has been described as

hypoplastic (Nager and de Reynier, 1948). Fusion of the squamous temporal sutures has been reported (Kreiborg and Bjork, 1982). There is little information in the literature about the

detailed pathology of the temporal bone in Crouzon syndrome. In this study, 2 pattems have emerged. The first is the typical pattern, the features of which are listed below. This pattern reflects the dysmorphic growth of the Crouzon cranium. The mechanisms by which the abnormality of the sutures determine the shape of the temporal bone are less clear due to the complex shape of the bone. The shape and position is also influenced by the growth distortion of the surrounding bones.

The sutural patterns of the temporal bone were more difficult to identify than any other bone, particularly laterally where the cranial base meets the calvaria due to their complex pattern. For this reason it was difficult to implicate the sutures as being distorted, although it seems likely that they are.

Narrowing of the jugular foraminae was a consistent finding and may have several effects such as producing a reduced intracranial outflow with reduced reabsorption of cerebrospinal fluid contributing to ventriculomegaly or hydrocephalus. Other extracranial-intracranial venous communications may become more prominent. Bleeding from these regions and from the venous sinuses may be more pronounced during surgery in this population. This has not been clinically recorded, however, brisk bleeding in the region of the orbits and from the dura has been our experience in some cases. [t is probable that any changes to intracranial dynamics are relatively subtle and these changes are difficult to measure.

The second pattern of the temporal bone is proposed due to the atypical findings in Patient HC with atresia of the external ear canal. The relevant feature about this patient was that while

Page 406 Crouzon Syndrome deformity was found in all regions of the bone, the dimensions of the bone were reduced. The sutures of the spheno-occipital synchondrosis were shortened and the temporal bones were closer together. The anterior petrous temporal sutures were reduced in length while the posterior sutures were increased, implying a more profound posterior process. The pattern profile was similar to the other patients but translocated to a reduced size position implying hypoplasia of the bone. This may reflect a primary growth abnormality of the petrous bone along the lines of a clefting process. Clearly, analysis of further patients with atresia or stenosis of the external auditory canal is required to determine whether this pattern holds true for others.

Summary of Deformitv:

I Typical Pattern

Calvarial suture involvement

Normal or prominent mastoid process

Distorted external auditory meatus (with increasing age)

Zy gomatic proces s s hortened

Narrowed j ugular foramen

Cranial base sutures lengthened or normal (variable combinations)

Generally broad inter-temporal distances

Variable angles of splay of the bones

2 Atretic Pattern

Calvarial suture involvement

Normal or prominent mastoid process

Stenotic or atretic external auditory meatus

Zygomatic process normal or lengthened

Normal or narrow jugular foramen

Cranial base sutures shortened anteriorly, lengthened posteriorly

Narrow inter-temporal distances

Variable angles of splay of the bones

Chapter 3 Page 407 3.5.10 The Morphology of the Parietal Bone in the Eight Patients with Crouzon Syndrome

The sutures outlining the parietal bone could not be identified in the Crouzon population due to

the pathology.No reliable landmarks could be identified adjacent to allow any measurements to

be accurately recorded. As a result no data has been produced for a region which clearly has pathology.

3.5.11 The Morphology of the Occipital Bone in the Eight Patients with Crouzon Syndrome

Distances: The majority_ of the measured distances were nonnal. All the distances in the

2 infants were all in the normal range. Increase in the length of the petrous temporal-occipital

suture was found in 4 patients, either bilaterally or unilaterally, with the trend to be increased on

the other side. The foramen magnum was reduced in size in 1 patient, yet nearly all patients tended to have reduced distances in this region. The foramen magnum was distorted in 2 patients with some asymmetry of shape.

Dimensions: The internal occipital protuberance was usually normally positioned. On 3 occasions the position was atypical, and reflects some shape variation in the posterior cranial fossa.

Discussion: The occipital bone is a large curved squamous bone which articulates with the

sphenoid, temporal and parietal bones. Measurement is made difficult due to difficulty

identifying the calvarial sutures. From plain radiographs and qualitative data, the lambdoid suture is the least commonly involved in Crouzon syndrome. Measurement of the dimensions of the posterior fossa is unreliable due to difficulty in landmark location on the large curved surface. The measurements therefore concentrate on the cranial base, the sutures with the temporal bone and the foramina. The relationship with the temporal bone determines the majority of the measurements.

The petrous temporal-occipital suture tended to be variable in length, and was considered in conjunction with the other distances representing the suture (fm-peta, peta-pts) which are

Page 408 Crouzon Syndrome described in the temporal bone, sphenoid bone and the cranial base sutures (Sections 3.5.8, 3.5.9, 3.5.12 respectively).

The spheno-occipital synchondrosis tended to be reduced in length and increased in height in the older patients (Patients IP, L'W, AY, HC and TS). A complete description of the synchondrosis is given in the description of the sphenoid bone (Section 3.5.8) and cranial base sutures (Section 3.5 .12).

The jugular foramen consistently had reduced distances, representing narrowing of the foramina. This was also seen qualitatively. Reduction in venous outflow has been considered a possible cause of raised intracranial pressure, hydrocephalus or ventriculomegaly in Crouzon syndrome. Narrowing of the foramina has been statistically demonstrated in some patients.

Collection of more data and comparison with ventricular findings may further elucidate any correlation.

Variable asymmetry was seen at the foramen magnum and appeared to represent a distortion of the lateral margins of the foramen. There is no clear explanation for this but bone resorption may be involved and may be increased with raised intracranial pressure. Underlying central nervous system abnormalities such as tonsillar herniation (David et a1., 1982) may also distort bony shape. In this study CNS abnormalities were not detected in this region in these patients.

Summary of Deformity:

I . Petrous temporal-occipital suture length variable.

2. Spheno-occipitalsynchondrosisshapedistorted.

3 . Narrow jugular foramen

4. Variable asymmetry at foramen magnum

3.5.12 The Morphology of the Cranial Base Sutures in the Eight Patients with Crouzon Syndrome

Anterior Cranial Fossa: The commonest region of deformity was at the spheno-ethmoid synchondrosis. This was demonstrated in 4 patients (Patients IP, LW, AY and HC). These

Chapter 3 Page 409 patients were 4 of the 5 oldest in the group. The oldest patient (Patient TS) had no spheno- ethmoid involvement but involvement laterally in the region of the fronto-ethmoid suture was found (Sections 3.5.3 Frontal bone, 3.5.7 Ethmoid bone). The spheno-frontal sutures measured in the anterior cranial fossa and in the orbit showed only slight and infrequent variation from normal. Laterally the spheno-zygomatic suture was increased in length in 4 patients and is discussed in patterns of zygomatic suture involvement (Section 3.5.4 Zygomatic

Bone).

Middle Cranial Fossa: The sutures were relatively normal in the floor of the middle cranial fossa, with increased spheno-petrous temporal suture length the commonest finding in the older patients.

Posterior Cranial Fossa: The sutures were lengthened either medially (Patients SH and HC), laterally (Patients JS and TS) or with a combination of both (Patients IP, LW and AY). Patient

RN had normal suture lengths. In the older patients, the spheno-ethmoid synchondrosis involvement occurred in a particular pattern. The region was reduced in width and increased in height. This was reflected in the measurements in 2 ways. Firstly, the height was increased and the width was normal (Patients IP, LW and AY). Secondly, the height was nonnal and the width was reduced (Patients HC and TS), These measurements produce a similar shape but a relative size reduction.

Discussion: A pathological process in Crouzon syndrome occurs both at the suture and synchondrosis. What drives this event is not clear. Its timing and severity are also poorly understood. The cause and effect relationship between the role of cranial bone growth and the sutural fusion in Crouzon syndrome has yet to be determined. Variability of calvarial suture involvement,however, typically occurs. The same can be said of the cranial base sutures and synchondroses. The spheno-ethmoid synchondrosis appears to be involved, and is thought to be instrumental in normal midfacial development (Enlow, 1975; Burdi et al., 1986). The distance representing the spheno-ethmoid synchondrosis was lengthened in 4 patients (Z score

> 1.96). The clinical effect of this lengthening and presumed premature fusion was the reduction of the forward growth of the ethmoid with deflection of growth laterally. Thus, the relationship of maxilla with the ethmoid shows it to be broad and positioned superiorly in

Page 410 Crouzon Syndrome Crouzon syndrome when compared with the experimental standard. Clinically the maxilla develops downward to produce a functional occlusion but has reduced growth in the AP direction.

The distance representing the spheno-zygomatic suture was significantly increased in 4 of the patients (Z score > 1.96). Fusion at this suture would account for the lack of AP growth and subsequent increased vertical length of the suture and contribute to the lack of bony support for the globe and thus proptosis. It would also contribute to the lack of forward growth of the greater wing of the sphenoid which may be a primary growth event or related to the involvement of the surrounding sutures such as the spheno-zygomatic, spheno-squamous temporal and, to a lesser extent, the occipital mastoid suture.

Examination of all the cranial base sutural measurements produced a picture of primarily anteriorandperipheralsutural involvement (Figure 3 46). The spheno-zygomatic and occipital mastoid sutures are essentially an extension of the calvarial sutures and anteriorly, the sphenoid-ethmoid synchondrosis is intimately related to maxillary development. The spheno- occipital synchondrosis proper, a site thought to play a major role in the cranial base pathology, was distorted but not greatly lengthened.

There was variation in which sutures were involved. This method of analysis allows specific identification of this variation in each patient producing a profile of involved regions. It should be noted that the more severe the deformity (Patient IP) and the older the patients (Patients LV/,

AY, HC and TS) the greater the chance of identifying abnormai sutural distances. Further population-based study with improved experimental standards is currently needed and provides

the focus of ongoing research.

3.5.13 The Morphology of the Craniofacial Dimensions and Angles in the Eight Patients with Crouzon Syndrome

Dimensions: The facial height from nasion to gnathion was increased in the older patients where

the landmarks could be reiiably assessed. Laterally, the height was closer to normal. The cranial

base dimensions were generally not significantly different from the experimental standard, with

the exception of Patient IP, who had the most distorted skull.

Clnpter 3 Page 411 Angles: The SNA angles were low-normal or reduced and reflected the midface hypoplasia.

Additionally, the cranial base angle and the subsequent position of the sella-nasion line,

influenced the angle. The SNB angles appeared to follow a similar pattern, although they could not be assessed in the younger patients.

The cranial base angles varied from increased (Patients IP, HC and TS), to normal (patients

RN and JS) to reduced (Patienrs SH, LW and Ay).

Discussion: The cranial base angles vary. This finding has been described previously by others (Kreiborg, 1981). This interesting feature highlights two points. Firstly, the evolution of the pathology may occur at different rates and with different severity at different locations, in a

similar way to the varied pathology of the cranial sutures and resultant calvarial shapes.

Secondly, we need to look for not a single pattern of clinical and measured deformity in

Crouzon syndrome, but rather for a range of patterns. It is probable that some pattems of the

deformity are more common than others. This thesis attempts to identify some of these patterns.

The significance of the cranial base pathology should be related to the surrounding pathology

and resultant deformity. The primary growth of the cranial base may be distorted by a primary

growth disturbance of the bones or synchondroses and sutures. Secondary distorting forces

include the effect of adjacent bone deformity and the intracranial pressure.

3-6 Theory of Pathogenesis of Craniofacial Morphology in Crouzon Syndrome

The pathogenesis of the deformities in Crouzon syndrome is not fully understood. Two main theories currently exist. The first theory evolved from initial observations of deformity in the simple craniosynostoses and proposes that the primary defect is at the level of the suture. Premature suture fusion results in bony deformation which is readily demonstrable at the calvarial level. In contrast to simple craniosynostosis disorders, the premature suture fusion extends into the cranial base having a compounding effect on the morphology at this level. In addition, raised intracranial pressure exerts forces that alter the dynamic morphology of the cranial base bones. The resultant cranial base changes have a secondary effect on the orbital and maxillary manifestations. Recent 3D CT qualitative descriptions by Kreiborg et al. (1993) have postulated a sutural abnormality and demonstrated secondary cranial base changes from

Page 412 Crouzon Syndrome pressure. This is in contrast to Apert syndrome where a primary defect of cartilaginous bone has been implicated.

The second theory proposes that the premature suture fusion occurs in response to external forces. The postulated primary event is a spatial malpositioning or abnormal dural stresses acting on the calvarial sutures. This theory is based on animal studies and fetal examinations where typical calvarial deformities may be present, but the cranial sutures are patent (Moss,

19s9).

This study has demonstrated, by quantification, the pathology of Crouzon syndrome. The results are summarised in Table 3.3 and are represented diagrammatically in Figures 3.35 -

3.46 (comparisons of each patient with the experimental standard are to scale, comparisons between the age groups are not to scale).

The interpretation of the morphological quantification identified the pathology at the level of the suture but at the same time found regions of primary bony dysplasia. Differentiation between the 2 theories of pathogenesis cannot be conclusively demonstrated by qualitative and quantitative assessment, particularly at the level of the cranial base. Primary bone growth and suture function are intimately related and both contribute to morphology. Both of these features can be considered primary abnormalities in Crouzon syndrome (Figure 3.47). The premature suture fusion accounts for the typical shape distortion of the calvarial bones, however, dysplasia of bony elements in the cranial bones has also been identified and is less clearly the result of pathology of adjacent sutures and synchondroses. In addition, the present study identified pathology at some but not all cranial base sutures. In addition, the pattern of distortion of the cranial bases is not uniform. In this study, for example, external auditory meatus atresia seen in 1 patient was correlated with hypoplasia of the petrous temporal bone.

In addition reduced size of foraminal openings was a prominent feature of the disorder. As mentioned above the external auditory meatus may be stenosed or atretic. The jugular foramen was found to be narrowed in virtually all patients. Similarly the superior orbital fissure was shortened in the majority. The diameter of the optic canai was not assessed, due to difficulty in visualisation, but clearly is a relevant dimension in relationship to the progressive optic atrophy

Chapter 3 Page 413 that is found in Crouzon syndrome and of the risk of the optic nerve traction at the time of surgical manipulation.

The abnormal shape of the bones appears to be related to both primary developmental and

secondary deforming factors (Figure 3.47). Secondary morphological features complicate the

dysmorphology in Crouzon syndrome and these are considered as the interactions between

structures. Deformity of one bone exerts a deforming force on its adjacent neighbour not only

by its sutural attachment but by its bulk and direction of growth. This is most clearly seen in the

zygomatic bone where its position and shape are affected not only by the adjacent sutures but

by the projection of the greater wing of the sphenoid and calvarial deformities. The effect of the

brain on adjacent bones either at normal or raised intracranial pressure exerts some deforming

effect. Endocranial bony resorption and scalloping has been well described. The enlargement of

the sella turcica in the body of the sphenoid can be demonstrated on CT scans (Kreiborg et al.,

1993) and is presumed due to bony resorption secondary to pressure. Thirdly the effect of the

functional matrix (Moss and Salentijn, 1969; Moss, I9'7I,1975) has relevance particularly at

the occlusal level. Increased alveolar height, and the retroclined position of the mandibular

symphysis attempt to form a functional occlusion.

Added to this complex picture are the effects of growth. Calvarial growth is more rapid in

infancy and greater deformities are seen at this time. Later in childhood maxillary deformity becomes more evident.

In conclusion, the nature of primary bony abnormality influencing sutural development cannot be determined without histochemical analysis. Several features, however, suggest this

interaction exists. Calvarial deformity may exist with the absence of sutural fusion and the pattern of sutural fusion is variable. The growth and development of the cranial base bone is not

normal and at times produces deformity not conelated with any detectable suture abnormality.

The assessment of the cranial bones is affected by the secondary forces which alter the primary pathology. Further study of all facets of Crouzon syndrome both clinical, radiological, histological, and genetic will lead to the determination of the fundamental pathological process.

Page 414 Crouzon Syndrome Crouzon syndrome

Patient LW Patient IP Patient TS 6 years 2 years Adult

minimal deformity increased intercondylar increased intergonial distance distance

Experimental standard

6 years 2 years Adult

Figure 3.35 Pattern of deformity of the Mandible in Crouzon syndrome. (Each age group independently scaled.)

Crouzon syndrome

Patient IP Patient TS Increased height Adult 2 years Reduced AP dimension

Experimental standard

2 years Adult

Figure 3.36 Pattern of deformity of the Maxilla in Crouzon syndrome. (Each age group independently scaled.)

Frontal-ethmoid attachment Viewed from above

posterior

Crouzon syndrome

Patient TS w Adult 6 years increased width and reduced increased width and length length

Experimental standard

anterior 6 years Adult

Figure 3.37 Pattern of deformity of the Frontal bone in Crouzon syndrome. (Each age group independently scaled.)

Crouzon syndrome

Patient LW Patient HC 6 years Adult Fronto-zygomatic pattern Spheno-zygomatic pattern

Increased width Increased vertical height Reduced AP length

Experimental standard

6 years Adult

Figure 3.38 Pattern of deformity of the Zygomatic bone in Crouzon syndrome. (Each age group independently scaled.)

Crouzon syndrome

Patient LW 6 years Adult Vomer relatively normal Vomer angled inferiorly

Experimental standard

6 years Adult

Figure 3.39 Pattern of deformity of the Vomer and Ethmoid bone in Crouzon syndrome. (Each age group independently scaled.)

Viewed from behind

Crouzon syndrome

Patient LW Patient TS 6 years Adult Reduced height of lateral plates Increased width frontal ethmoid attachment

Experimental standard

6 years Adult

Figure 3.40 Pattern of deformity of the Ethmoid bone in Crouzon syndrome. (Each age group independently scaled.)

Anterior aspect

Crouzon zl syndrome

Patient LW 6 years

Lesser wing position variable Lateral projection of greater wing

Experimental +- standard -

6 years

Figure 3.41 Pattern of deformity of the Sphenoid bone in Crouzon syndrome.

Patient LW Patient TS 6 years Adult Crouzon syndrome

Lateral projection of greater wing from origin at body Posterior angulation of pterygoid plate

rl Experimental I standard 6 years Adult

Figure 3.42 Pattern of deformity of the Sphenoid Greater Wing and Pterygoid Plate in Crouzon syndrome. (Each age group independently scaled.)

Crouzon syndrome

Patient TS Adult Increased width Decreased height Increased sella size

Experimental standard Adult

PA view Lateral view From above

Figure 3.43 Pattern of deformity of the Sphenoid Body in Crouzon syndrome.

Crouzon syndrome Experimental standard Patient I{C Patient TS Adult Adult Adult Posterior View

pattern synchondrosis Lateral View Variable at spheno-occipital

Figure 3.44 Pattern of deformity of the Sphenoid Body and Temporal bone in Crouzon syndrome.

Left Right

Patient HC Reduced size Adult F { Crouzon syndrome

Patient TS Shape distortion Adult f Borderline reduced size

Experimental standard Adult q

Figure 3.45 Pattern of deformity of the Jugular Foramen in Crouzon syndrome.

Lateral aspect Crouzon syndrome Experimental standard Patient HC Adult Adult

anterior anterior

posterior middle posterior middle

Superior aspect anterior anterior

middle middle

posterior posterior , - -

Figure 3.46 Pattern of deformity of the Cranial Base Sutures in Crouzon syndrome.

Primary Events

Primary bone dysplasia Premature synostosis and Growth

Calvarial distortion

Cranial base bone hypoplasia/dysplasia

Stenosis of cranial meati (EAM, jugular, sup. orb. fissure)

Secondary Events

Distortion from adjacent bones (indireclnon-sutural)

Brain and intracranial pressure effects (endocranial resorption)

Functional matrix factors (occlusion)

Figure 3. 47 Theory of Pathogenesis of Morphology in Crouzon Syndrome

CHAPTER 4

THE THREE DIMENSIONAL QUANTITATIVE ANALYSIS OF THE CRANIOF'ACIAL MORPHOLOGY BEFORE AND AFTER SURGERY IN CROUZON SYNDROME

4.1 Introduction

Dysmorphology of the craniofacial skeleton in Crouzon syndrome has been extensively examined in the preceding chapter with the aim of analysing the underiying pathology. The quantitative analysis was based on the determination of the position of anatomical landmarks in

3D. This method of analysis has 2 other main applications. These are the assessment of craniofacial growth in this (and other) conditions as well as the normal population and the analysis of the effects of surgical intervention which aim to release sutures and advance craniofacialbony elements. In the group of patients studied, there were no serial CT scans of patients to allow anaiysis of growth. However, CT scans were performed routinely tbllowing surgery and hence this data was available for analysis. The alteration of the craniofacial morphology by surgery, for either functional or aesthetic indications, is assessed in this chapter.

The techniques of craniofacial surgery were pioneered by Paul Tessier, and have since been expanded by many others. Many procedures have been described for functional and aesthetic indications. The broad principles and outline of surgical intervention are described in Chapter 2.

The priority of surgery is functional correction of the deformity. The aesthetic correction of the deformity a is desirable but secondary objective. In general, the age of the patient and the extent of the deformity will determine the type and timing of surgery. In infancy the fronto-orbital

advance is used to release the calvarial suture and provide protection for the globes. The

concept of the floating forehead (Marchac and Renier, 1919) aims to maximise the anterior

advancement by allowing brain growth to expand the calvarial bones. After 3 years of age brain expansion is less rapid and the effect of the floating forehead is less

dramatic. The fronto-orbital advance is also used in childhood for raised intracranial pressure

and globe protection. Mid-facial surgery is also possible in this age group (McCarthy et al.,

1e90).

In adults the definitive correction of the aesthetic deformity may be attempted. This has been

predominantly done using fronto-facial and [æ Fort III advancement. Variable osteotomy sites

lrave been suggested (Gillies and Harrison, 1951; Tessier, I9llb; Tessier, 1916; Ortiz-

Monasterio et al., 1978).

Problems with craniofacial surgery in Crouzon syndrome include relapse in the position of bony elements, recurrent synostosis with the growth of the patient and a failure to adequately correct a complex deformity with simple osteotomies. This last problem is highlighted by the difference between the good result in the simple craniosynostosis patients compared with the less satisfactory results in the syndromal synostosis patients.

In the past, assessment of surgery in Crouzon syndrome has been measured by cephalometry

(Bachmayer and Ross, 1986; Kaban et al., 1986; Kreiborg and Aduss, 1986; Ousterhout et al,

1986; Tulasne and Tessier, 1986; Ousterhout and Vargervik, 1987; David and Sheen, 1990) and more recently by two dimensional CT (Posnick et al., 1993).

Using the method and experimental standard data described in Chapter 3 of this manuscript, CT analysis was undertaken to provide further information on the craniofacial proportions following surgery. In particular, the pathology of the patient and the region undergoing surgery were analysed. The distance of movement of the surgical region was determined from the post- operative CT scan and the relationship of this new position was compared with the experimental standard data

This study represents the development of a new method of morphometric analysis of surgery utilising 3D CT reconstructions. The accuracy and the limitations of the method are determined.

The analysis aims to provide insights into the pathology ancl surgical manipulation for a greater understanding of the complex deformity.

Poge 432 Crouzott Syndrome 4.2 Materials

4.2.I Patient Selection

Five of the 8 patients whose craniofacial morphology was measured in Chapter 3, had conective surgery with post-operative CT scans, enabling analysis of the operative procedures.

A fronto-orbital advance had been performed in 3 patients (Patients SH, JS, IP). Another patient (Patient LW) had an extended fronto-orbital advance and a 15 year old male (Patient

HC) had analysis of a fronto-facial advance (Figures 3.2,3.3,3.4,3-5 and3.7).

The other 3 patients were not suitable for analysis. The post-operaúve CT scan for Patient RN was performed at age 10 months while the pre-operative scan was performed at 1 month and these were not considered comparable due to the gro\üth changes during this time period

(Figure 3.1). Patient AY had had no surgery due to a mild degree of deformity and Patient TS did not have a satisfactory post-operative CT scan (Figures 3.6 and 3.8). Details of the patients

and the sugery performed are shown in Table 4.1.

Table 4.1 Details of 5 Patients with Crouzon Syndrome undergoing Surgery Ages

Category Name Sex Surgery Age at CT Surgery Post-op scan CT scan

6 months SH F FOA 5 months 7 months 8 months

2 years JS F FOA 21 months 21 months 22 months

2 years IP M FOA 21 months 21 months 22 months

6 years LV/ M Extended 5.5 years 5.7 years 6 years FOA

Adult HC M FFA 15 years 15 years 15 years

Chapter 4 Page 433 There was inadeqùate CT data available for long term follow up. This was relevant in the adult patient studied where degree of relapse and long terrn outcome could not be fully assessed. In children and especially in infants assessment of long term follow up may be confounded by growth. Despite these difficulties the assessment of surgery in this study provides immediate information about the surgery performed and allows analysis of whether the surgical aim was achieved in the short term.

4.2.2 Experimental Standard

The experimental standard used in Chapter 3 was utilised for comparison with the pre- and post-operative positions.

4.3 Method

4.3.t CT Scan Protocols and Reconstructions

The pre- and post-operative CT scans and the experimental standard CT scans were performed accordingtotheprotocolsoutlined in Chapter 3 (Sections 3.3.1 CT Scan Plotocols, 3.3.2 3D

CT Sc¿ur Reconstruction and Interpretation).

4.3.2 Definition of Surgical Units

The bony structure of the region undergoing surgery is represented by the relevant landmarks and lines drawn between the landmarks. This diagrammatic representation is termed the

"surgical unit" and are described in the following Sections 4.3.2.1-3 and in Figures 4.1-3.

4.3.2.1 Fronto-orbital Advance

The fronto-orbital advance entails a forward shift of the frontal bone with part of the ethmoid.

The aim is to gain a forward advance of between l-2 cm, thereby releasing the cranial sutures and providing protection for the globes. This is usually in 2 pieces: the frontal bone plate and the fronto-orbital bar (the supra-orbital ridges). Part of the nasal bones, the ethmoid, the zygomatic bone and their relevant sutures may be involved in the surgical cuts to a greater or lesser extent. The area involved cannot be simply described using the previous landmark definitions from Chapter 3. In order to compare the pre- and post-operative structures,

Page 434 Crouzon Syndrome landmarks were identified whioh could be seen on both pre- and post-operative images and were representative of the surgery performed. It is diffrcult to visualise the calvarial landmarks of the frontal bone fully, due to fusion of the sutures at the fronto-zygomatic, fronto-sphenoidal and fronto-parietal regions and this region was excluded in this study. However, the supra- orbital ridge has readily reproducible landmarks on pre- and post-operative CT scans and also on the normal standards. A comparison of the position of these landmarks also provides the best guide to the functional success of the operation as the surgical movement of the supraorbital ridge aims to cover the proptosed globes and provide room for forward brain expansion and growth. The fronto-orbital bar was used as the bony component representing the fronto-orbital advance. Landmarks on this area are defined and shown in Figure 4.i. Lines were drawn between the landmarks to provide an outline of the bone component to enable visualisation of the surgical unit.

During surgery remodelling of the shape of the fronto-orbital bar occurs. At operation, the frontal bar is divided in the middle and in the region of the lateral corner of the supra-orbital rim. It is rejoined with a more obtuse angle, centrally and a more acute angle, iaterally. This brings the lateral segments forward to a greater extent than the central parts. A change in shape is therefore expected in the post-operative surgical unit.

4.3.2.2 Extended Fronto-orbital Advance

The extended fronto-orbital advance is defined, for the purposes of this project, as the surgical

advancement of the supra-orbital ridge, the frontal bone and also the bodies of the zygomatic

bones. This procedure has the effect of advancing the lateral orbital wall and the mala¡

eminence, along with the supra-orbital region. The aim is similar to that of the fronto orbital

advance in gaining a forward advance of between I - 2 cm. The fronto-orbital bar and the

zygomatic bones combine to make the bone component of the extended fronto-orbital advance.

The frontal bone plate has again been excluded due to diff,rcuit calvarial landmark identification.

The landmarks for this surgical unit are defined and shown in Figure 4.2.

Chapter 4 Page 435 4.3.2.3 Le Fort III Advance

The Le Fort III advance is ¿ur advancement of the maxilla and upper dentition at the level of the orbits and the ethmoid. For the analysis of the læ Fort III advance, landmarks from the facade of the maxilla were recorded to represent the surgical unit. The landmarks are dehned and shown in Figures 4.3a and 4.3b. One patient (Patient HC), underwent a fronto-facial advance derived from the addition of the landmarks for the Le Fort III advance to those of the fronto- orbital advance. This procedure was planned using standard orthognathic techniques with an anterior shift at the occlusal level of 14 mm.

4.3.3 Alignment of Surgical Units

Alignment of the surgical units on each other for comparison, required the definition of landmarks which were not involved in the surgical process. These were found most readily in the cranial base.

4.3.3.1 Cranial Base Unit

The cranial base landmarks selected for alignment were readily identifiable points which were equally spaced across the cranial base. These include the foramen magnum, the foramen ovale, the mastoid process, the porion and auriculare points. The landmarks for alignment for the cranial base alignment unit are defined in Figures 4.4a and 4.4b. Virtually any alignment points selected are involved in the pathology in Crouzon syndrome, as demonstrated in Chapter 3. The cranial base points were chosen as they were readily identifiable, remote from the surgical location and therefore not affected by it. They do, however, reflect the cranial base pathology.

Compared with the experimental standard, small discrepancies at the level of the cranial base may manifest themselves as larger, more extreme changes, when the alignment is used as the reference for the anterior craniofacial surgical units. This limitation exists whatever landmarks are used for comparison due to the generalised pathology of the craniofacial skeleton in

Crouzon syndrome.

Page436 CrouzonSyndrome 4.3.4' Landmark Identification and Accuracy

The method and the determination of the accuracy of the landmark identification for the surgical units is the same as that used in Chapter 3 (Sections 3.3.6 Method of Landmark ldentification,

3.3.7 Landma¡k Accuracy). Landmark accuracy for all points is listed in Appendix 1.

4.3.5 Analysis of CT Data

For each of the five patients, landmarks representing the relevant surgical unit for the patient, along with the craniat base alignment unit were recorded from the pre- and post-operative CT scans and from the CT scans of age-matched normal skulls (as discussed in Chapter 3).

A longitudinal study, in three pafts, was made by comparing: a) The pre-operarive shape and position of the surgical unit of the patient with that of the

corresponding surgical unit of the averaged normal skulls (experimental standard). This

analysis provided additional visual and measurement data on the pathological

morphology of Crouzon syndrome, described in Chapter 3. b) The pre-operative shape and position of the surgical unit with the post-operative surgical

unit. This assessed the direction and maintenance of the surgical manoeuvre. c) The post-operative shape and position of the surgical unit with the surgical unit of the

experimental standard. This was to determine whether the surgical manoeuvre had

shifted the surgical unit any closer to the ideal structure, as represented by the data for

the normal skulls.

4.3.6 Comparison of Surgical Unit Data

The data from the measurement of the landmarks of the six normal conEol dried skulls were

averaged, taking into account the error of landmark identification. This produced 1 set of

landmark data which was used in the visual and statistical assessments of the surgical

comparisons. The CT scan landmarks of each patient were aligned with those of the relevant

experimental standard using the cranial base alignment unit (Figure 4.5). This was performed

using the least squares (procrustes method) and repeated median methods of alignment (Rohlf

Chapter 4 Page 437 and Slice, 1990; Èookstein, 1991). Having aligned the skulls on their cranial base units, the surgical units being compared were then viewed which enabled immediate appreciation of surgical shifts In addition to visualisation of the surgical units (Figures 4.5 - 4.11), the differences between the surgical units was measured.

Measurements were made in 2 ways. Firstly, the distance between the same landmark on each surgical unit was measured with the greater differences representing a greater degree of deformity from either normal or from the pre-operative position. Secondly, registration to "best fit" the two surgical units together was performed, using the least squares and repeated median methods. By performing this function, the averaged or mean translocation for one surgical unit to move and align itself on the other was represented. This translocation analysis has been used as an index of misrnatch of the two surgical units under comparison. The registration provides the orientation and translation differences. The rotation matrices are near normal (rotations of only a few degrees). The translations are given in Appendix 3. The vectors of displacement are positive when to the right, anterior or superior. Negative displacement vectors are to the left, posterior or inferior. This analysis was performed for the 3 comparisons that were described in the previous section.

In the first analysis (pre-operative surgical unit vs standard surgical unit) the distances and translation represent the deviation of the pre-operative surgical unit from the standard surgical unit. In the second analysis (pre-operative surgical unit vs post-operative surgical unit) the distances and translation represent the movement of the surgical unit following surgery. In the third analysis (post-operative surgical unit vs standard surgical unit) the distances and translations represent the residual deformity of the surgical unit compared with the standard surgical unit.

Page43B CrouzonSyndrome Figures 4."1, - 4.4 Diagrammatic representations of the Surgical Units and Alignment Units showing the Landmarks identified

Chapter 4 Page 439 Legend for Figure 4.1 Fronto-orbital Advance

û b glabella: The most prominent point in the mid-sagittal plane between the eyebrow ridges (see frontal bone).

sorl/sorr superior orbitale left/right: The most superior point on the supra-orbital margin (see frontal bone).

s I orsl/slorsr supero-lateral orbitale superius left/right: The same point as the superoJateral orbitale in the unoperated state ie The intersection of the fronto-zygomatic suturè with the lateral orbital rim (almost the intersection of the curve of the supra-orbital rim with the lateral orbital rim (see frontal and zygomatic bone). In the post-operative state the point is annotated as 'superius' to differentiate it from the inferior region which may not ñave been shifted surgically.

smorl/smorr supero-mediale orbitale left/right: The most superior and medial point on the orbital rim midway between the superior and medial orbitale points.

zfsl/zfs r zygo-frontale superius left/right: The same point as the zygo-frontale in the unoperated state ie the point located at the posterior extremity of the fronto-zygomatic suture (see frontal and zygomatic bone). In the post-operative state the point is annotated as 'superius' to differentiate it from the inferior region which may not have been shifted surgically.

Legend for Figure 4.2 Extended Fronto-orbital Advance o glabella: The n-rost prominent point in the mid-sagittal plane between the eyebrow ridges (see frontal bone). ilorl/ilorr infero-lateral orbitale left/right: The point is determined approxinrately mid-way between the sutures lirniting the zygomatic bone or, alternatively, at the intersection of the anterior projection of the maxillary border of the inferior orbital tìssure with the lateral orbital rim. orl/orr orbitale left/right: The most inferior point on the infraorbital margin. parl/parr pre-articulare left/right: The most superior point on the lower border of the zygomatic arch located anterior to point articular eminence sorl/sorr superior orbitale left/right: The most supelior point on the supra-orbital margin (see frontal bone). sloll/slorr supero-lateral orbitale left/right: The intersection of the fronto-zygomatic suture with the lateral orbital rim (almost the intersection of the curve of the supra-orbital rim with the lateral orbital rim. smorl/smorr supero-mediale orbitale left/right: The most superior and medial point on the orbital rim midway between the superior and medial orbitale points. zil/zfr zygo-frontale left/right: The point located at the posterior extremity of the fronto- zygomatic suture. zmillznir zygomaxillare inferius left/right: The lowest point on the exte¡nal suture between zygomatic and maxillary bones.(in the region of the craniometric landmark, zygomaxillare). ztllztr zygo-temporale lcft/right: The mid-point of the bony concavity forn-red between the frontal and temporal processes of the zygomatic bone.

Page 440 Crouzon Syndronte Figure4.L: Fronto-orbitalAdvance (anterior aspect) Surgical Unit

s sorf o sorl

Figure 4.2: Extended Fronto-orbital Advance (anterior aspect) Surgical Unit

I sorr a sorl

porf

zmill

Chapter 4 Page 441 Legend for Figure 4.3 Le Fort III Advance

all/alr alare left/right: The most lateral point on the anterior nasal aperture.

ans anterior nasal spine: The apex of the anterior nasal spine. (Also known as spinal point (sp) or acanthion (ac)).

cs l/csr canine superius left/right: The tip of the buccal cusp of the maxillary canine.

dmsl/dmsr disto-molare superius left/right: The disto-buccal cusp of the maxillary first molar. ecsl/ecsr ecto-canine superius left/right: The most anterior point on the alveolar ridge, opposite the centre of the maxillary canine. eicsl/ei csr ecto-incision central superius teft/right: The most anterior point on the alveolar ridge, opposite the centre of the maxillary central incisor. emlsl/em1sr ectomolare lst superius left/right: The most lateral point on the alveolar ridge, opposite the centre of the maxillary first molar. gpfl/gpfr greater palatine foramen left/right: The centre of the greater palatine fbramen. isl/isr incision superius left/right : The mid-point of the incisal edge of the maxillar-y central incisor. i I o rl/ilorr infero-lateral orbitale left/right: The point is determined approximately mid-way between the sutures limiting the zygomatic bone or, alternatively, at the intersection of the anterior projectiou of the maxillary border of the inferior orbital fissure with the lateral orbital flm.

I orl/lorr lateral orbitale left/right: The nost lateral point on the orbital rim. mxtl/mxtr maxillary tuberosity left/right: The most postero-inferior point in the midline of the maxillary tuberosity. morl/morr medial orbitale left/right: The most medial point on the orbital rnargin in the region of the fronto-lacrimal suture. (Located near the craniometric point Dacryon). mmlsl/mmlsrmedio-molare lst superius left/right: The tip of the medio-buccal cusp of the maxillary first molar. na nasale: The tip of the nasal bone. n nasion: The most anterior point of the frontonasal sutul'e. (If suture not clearly identified then the deepest point on the nasal notch can be substituted in the midline.) nlil/nlir naso-lacrimal inferius left/right: The most antero-inferior point on the margin of the naso-lacrimal gloove as iL exits ihe orbit (usually this point is located at the small spicule of bone covering the lateral wall of the naso-lacrimal groove ancl the inferior orbital rim)- orl/orr orbitale teft/right: The most inferior point on the infraorbital margin. pns posterior nasal spine: The apex of the posterior nasal spine. pr prosthion: The most antero-inferior point on the maxillary alveolar malgin in the mid- sagittal plane. ss subspinale: The most posterior point on the anterior contour of the rnaxillaly alveolar process in the mid-sagittal plane. (Also known as Down's Point A). snml/snmr superior ¡raso-¡naxillare left/right: The most superior point on the naso-maxillary s uture. slorl/slorr supero-lateral orbitale left/right: The intersection of the fronto-zygomatic suture with the lateral orbital rirn (almost the intersection of the curve of the supra-orbital rim with the lateral orbital rim.

Page 442 Crouzon Syndronrc Figure 4.3(a): Le Fort III Advance (anterior aspect) Surgical Unit

ou c qrr qll '

zm[ zmil ecsf pr

Figure 4.3(b): Le Fort III Advance (left lateral aspect) Surgical Unit

ons mxll ss zmil ecsl eml sl pr

Chøpler4 Page443 Legend for Figure 4.3 Le Fort III Advance (continued)

zil/zfr zygo-frontale left/right: The point located at the posterior extremity of the fronto- zygomatic suture.

zmillzmir zygomaxillare inferius left/right: The lowest point on the extemal suture between zygomatic and maxillary bones.(in the region of the craniometric landmark, zygomaxillare).

ztllztr zygo'temporale left/right: The mid-point of the bony concavity formed between the frontal and temporal processes of the zygomatic bone.

Legend for Figure 4.4 Cranial Base Atignment Unit acl/acr anterior clinoid left/right: The most posterior point on the anterior clinoid of the lesser wing of the sphenoid bone. In the cases of bridging between the anterior and posterior clinoid the point is determined at the anterior prominence mid-way along the bridge. aul/aur auriculare leflright: The most superior point on the root of the zygomatic arch nearest to craniometric point porion. ba basion: The mid-sagittal point on the anterior margin of the foramen magnum (determined as the point of maximum convexity on the clivus of the skull at the anterior margin of the foramen magnum). pol/por external auditory meatus superius (ie porion) left/right: The most superior point on the margin of the external auditory meatus. fmll/fmlr foramen magnum lateralis left/right: The most lateral point on the margin of the foramen magnum. foil/foir foramen in ovale leflright: The mid point of the internal opening of the foramen ovale. fool/fo o r foramen out ovale left/right: The mid point of the extemal opening of the foramen ovale, at the level of the skull base. mal/mar mastoidale leflright: The most inferior point on the mastoid process. o opisthion: The mid-sagittal point on the posterior margin of the foramen magnum. pcl/pcr posterior clinoid left/right: The most superior and lateral point on the posterior ctinoid s sella: The centre of the sella turcica.

Page 444 Crouzott Syndronrc Figure 4.4(a): Cranial Base Alignment (superior cranial base) Landmarks

ocr

Figure a.aþ): Cranial Base Alignment (inferior cranial base) Landmarks

a s

T \' e. /t, /\\ J \ I ì \"/ f _J \_

Chapter 4 Pøge445

6 months Patient SH

2 years Patient JS Patient IP

6 years Adult Patient LW Patient HC

AP Preoperative Legend: I Lateral I Standard

Figure 4.5 Cranial base alignment and surgical units for fÏve patients with Crouzon syndrome. Alignment performed on cranial base unit showing relative position of pre-operative (Crouzon) surgical unit (green) and experimental standard unit (red).

4.4 Results

4.4.1 Analysis of the Pre- and Post-operative Morphology of Patient SH

4.4.1.L Alignment of the Cranial Base Unit for Patient SH

For this patient, the post-operative scan was taken at 8 months of age, approximately 1 month after the surgery and 3 months after the pre-operative CT scan (Figure 4.5). This represents closer age-matching than for patient RN in the same age group.

Chaprer4 Page449 4.4.I.2 Comparison of the Surgical Units for patient SH

Pre-operative Surgicat unit vs standard Surgical unit (Figure 4.6a)

Thp cranial base angle in this patient was significantly reduced compared with the experimental

standard (Figure 3.5). Alignment of the surgical units using the cranial base resulted in an

inferior position of the surgical unit for Patient SH. Measurement distances between corresponding surgical unit points were between 8.0 mm and 15.1 mm (Appendix 3). The index of mismatch had a magnitude of 11.8 mm where the pre-operative surgical unit was displaced 2.9 mm to the left,0.3 mm anteriorly and 11.4 mm inferiorly from the standard surgical unit.

Pre-operative Surgical Unit vs Post-operative Surgical Unit (Figure 4.6b)

As seen on the lateral view and view from above, the post-operative surgical unit was advanced anteriorly a short distance only, relative to the pre-operative position. Measurements of between

4.'/ mm and 13.8 mm were recorded, but the index of mismatch had a magnitude of 8.5 mm and was predominantly due to a superior displacement of 7 .6 mm (Appendix 3). There was a

3.3 mm anteriordisplacement and a 1.5 mm displacement to the right. The lateral points were moved further than the medial points due to intra-operative bone reshaping. Due to the short delay between pre- and post-operative CT scans, the cranial base alignment units were very similar.

Post-operative Surgical Unit vs Standard Surgical Unit (Figure 4.6c)

The post-operative surgical unit was anterior to the standard surgical unit by between 8.2 mm and 12.3 mm with a mismatch of magnitude 10.0 mm (Appendix 3). This was comprised of an anterior displacement of 9.3 mm with 3.7 mm to the right and 0.1 rnm superiorly. Based on the images seen here, the surgical manoeuvre appeared to have advanced the supra-orbital bar into a satisfactory position. The superior surgical advancement compensated for the reduced cranial base angle.

Page 450 Crouzon Syndronte a) versus

AP Lateral

From Above Oblique

b) versus

AP Lateral

Above Oblique From

c) versus

AP Lateral

Oblique From Above

Figure 4.6 Comparison of Surgical Units for Fronto-Orbital Advance in Patient SH.

4.4.L.3 Summary of the Surgical Findings for Patient SH

The analysis in this patient was more successful than for Patient RN as the pre- and post- operative CT scans were performed temporally closer together. The size of the patient's pre- and post-operative surgical units were close to the experimental standard, tending to improve the comparison. The relationship between the cranial base pathology and the surgical unit resulted in the craniofacial facade being positioned below the experimental standard. However, surgery shifted the facade up (and forward) and could therefore be considered to have resulted in a more favourable anatomical result, although not necessarily clinically apparent. The superior displacement of the surgical unit may have been due to operative positioning of the surgical unit, the stability of the fixation method and/or the effects of scalp closure. Surgery altered only the facade of the craniofacial skeleton. The cranial base deformity persists and may further distort growth.

4.4.2 Analysis of the Pre- and Post-operative Morphology of Patient JS

4.4.4.1 Alignment of the Cranial Base Unit for Patient JS

The alignment of the cranial base in this patient was good with respect to both size and position

(Figure 4.5).

Chapter 4 Pctge 453 4.4.2.2 Comparison of the Surgical Units for patient JS

Pre-operative surgical unit vs standard surgical unit (Figure 4.7a)

The pre-operative surgical unit lay posterior and slightly superior to the standard surgical unit.

Distancesbetweenthelandmarksof thesurgicalunits of 4.9 mmandT.4mm wererecorded

(Appendix 3). The index of mismatch had a magnitude of 5.1 mm, where the pre-operative

surgical unit was displaced by 0.2 mm to the left,4.3 mm posteriorly and2.l mm superiorly.

Pre-operative Surgical Unit vs Post-operative Surgical Unit (Figure 4.7b)

The position of the post-operative surgical unit was anterior to the pre-operative position. A slight superior displacement of the supra-orbital ridge was also seen. Measurements of between

7.1 mm and 18.6 mm were recorded (Appendix 3). The index of mismatch had a magnitude of

10.5 mm, where the post-operative surgical unit was displaced by 0.7 mm to the right, 10.0 mm anteriorly and 3.0 mm superiorly.

Post-operative Surgical unit vs Standard surgical unit (Figure 4.7c)

The post-operative surgical unit lay anterior and superior to the normal or standard surgical unit. This represented an improvement from the pre-operative position where the supra-orbital bar was behind the standard surgical unit. Measurements were between 6.3 mm and 13.3 mm, with an index of mismatch of 7.8 mm (Appendix 3), where the post-operative surgical unit was displaced by 0.7 mm to the right, 6.5 mm anteriorly and 4.2 mm superiorly from the standard surgical unit.

Page 454 Crouzon Syndronte a) versus

AP Lateral

From Above Oblique

b) versus

AP Lateral

From Above Oblique

c) versus

AP Lateral

From Above Oblique

Figure 4.7 Comparison of Surgical Units for Fronto-Orbital Advance in Patient JS.

4.4.2.3 Summary of the Surgical Findings for Patient JS

The posterior position of the pre-operative surgical unit was advanced by surgery beyond the standard surgical unit. This was at the expense of some superior displacement. A satisfactory overcorrection \ryas achieved and was demonstrated in the post-operative photographs (Figure 3.3).

The discrepancies seen in the post-operative positioning demonstrate several points. The fronto- orbital advancement, while it advances the supra-orbital ridge, may also raise it up superiorly, perhaps worsening the degree of superior displacement of this region, compared with the normal. In addition, the lateral wings of the supra-orbital bar are advanced further forward than the medial part, that is, the supra-orbital bar is divided and the lateral elements swung forward.

In effect, this over-corrects the situation. In the pre-operative versus the standard figure, the shapes of the supra-orbital bars can be seen to be relatively similar, particularly when viewed from above. When the post-operative position is compared with the standard, the lateral elements are lateral and more anterior as a result of the surgical manoeuvre. Clinically, this structural change results in squaring of the frontal region. This feature was also seen in the pre- and post-operative comparison where the anterior movement was recorded. Fixation was maintained with miniplates and screws and more closely matches the desired anterior translocation of 1-2 cm.

4.4.3 Analysis of the Pre- and Post-operative Morphology of Patient IP

4.4.3.1 Alignment of the Cranial Base Unit for Patient IP

This patient had severe calvarial and cranial base deformities and the cranial base angle was increased. Subsequently, the alignment of the cranial base posteriorly was reasonable, but anteriorly, the increased cranial base angle resulted in the anterior craniofacial skeleton being well superior to the standard surgical unit (Figure 4.5).

Chapter 4 Page 457 4.4.3.2 Comparison of the Surgical Units for patient Ip

Pre-operative Surgical unit vs standard surgical unit (Figure 4.ga)

As mentioned previously, the pre-operative surgical unit lay superior to the standard surgical unit. It was also posterior to the experimental standard. The measurements between the landmarks were between 18.0 mm and 34.5 mm (Appendix 3). The index of mismatch had a magnitude of 24.5 mm where the pre-operative surgical unit was displaced by 2.9 mm to the right, 12.2 mm posteriorly and2l.0 mm superiorly.

Pre-operative Surgical Unit vs Post-operative Surgical Unit (Figure 4.8b)

The pre-operative surgical unit had been advanced a significant distance anteriorly to a position represented by the post-operative surgical unit. Measurements between 19.7 mm ap to 27 .4 mm were recorded (Appendix 3). The index of mismatch had a magnitude of 22.6 mm and was made up of a displacement from the pre-operative to post-operative position of 3.8 mm to the left, 18.1 mm anteriorly and 13.0 mm superiorly.

Post-operative Surgical unit vs standard Surgical unit (Figure 4.8c)

The post-operative surgical unit was superior and anterior to the standard surgical unit. It was also significantly larger than the standard surgical unit. Measurements between the landmarks were between 33.0 mm and 37.3 mm (Appendix 3). The index of mismatch had a magnitude of an average of 33.6 mm and was made up of a displacement of the post-operative surgical unit from the standard surgical unit of 0.6 mm to the left, 7.5 mm anteriorly and 32.8 mm superiorly.

Page 458 Crouzon Symlrome a) versus

AP Lateral

From Above Oblique

b) versus

AP Lateral

From Above Oblique

c) versus

AP Lateral

From Above Oblique

Figure 4.8 Comparison of Surgical Units forFronto-Orbital Advance in Patient IP.

4.4.3.3 Summary of the Surgical Findings for Patient IP

There was gross deformity of the craniofacial skeleton in Patient IP. The supra-orbital region was significantly enlarged and lay superior and posterior to the experimental standard. This region was advanced by surgery but the underlying cranial base pathology was not corrected and considerable deformity remained. Clinically, correction of raised intracranial pressure and protection for the globes was achieved (Figure 3.4). Release of the raised intracranial pressure may also have helped to maintain the anterior position of the frontal advance, although the extent of this effect cannot be quantified.

4.4.4 Analysis of the Pre- and Post-operative Morphology of Patient LW

4.4.4.1 Alignment of the Cranial Base Unit for Patient LW

Cranial base unit alignment was satisfactory (Figurc 4.5) with good correlation in the region of the foramen magnum and sella and other points. However, the cranial base angle was reduced, which was demonstrated by the relative anterior position of the basion, compared with the standard. Due to the comparable alignment of the remaining points of the cranial base unit, the projections of the pre-operative surgical unit and standard surgical unit showed close alignment medially, in the region of the nasion. This suggests that the pathology in this region was less severe and is confirmed clinically when viewing the prominent nasion in this patient (Figure

3.5).

Chapter 4 Page 461 4.4.4.2 Comparison of the Surgical Units for patient LW

Pre-operative surgical Unit vs standard surgical Unit (Figure 4.9a)

The pre-operative surgical unit was anterior to the standard unit in the midline, however

posterior to the standard surgical unit laterally. Measurements between the landmarks ranged

between 3.6 mm and 16.2 mm (Appendix 3). The forehead was broader and slightly larger than

in the control. Despite the often large measurements, the index of mismatch had a magnitude of

1.6 mm where the pre-operative surgical unit was displaced by 0.5 mm to the right, 1.3 mm

posteriorly and 0.7 mm inferiorly. Despite achieving a best fit by a translocation of only 1.6

mm, there were many points which were large distances from the corresponding point in the

control but which could not be accommodated due to the differing shapes of the structure.

Pre-operative Surgical Unit vs Post-operative Surgical Unit (Figure 4.9b)

A comparison of the position of the post-operative surgical unit with the pre-operative position highlighted the anterior shift of the supra-orbital ridge with a greater anterior shift of the extended part of the fronto-orbital advance, that is, the zygomatic bodies. The distances between landmarks were 1.6 mm for the glabella and up to 20.5 mm for the pre-articulare point on the right.

The majority of the measurements were between 3 and 10 mm with the greater distances occurring lateraily (Appendix 3). The surgical objective of advancing the lateral elements a greater distance anteriorly was achieved. However, the index of mismatch had a magnitude of

6.1 mm with a 0.8 mm displacement to the right,5.3 mm anteriorly and 3.0 mm superiorly.

Post-operative Surgical unit vs Standard Surgical Unit (Figure 4.9c)

The post-operative surgical unit was anterior to the standard surgical unit, and was seen best on the lateral view and in the view from above in Figure 4.9c. The lateral orbital walls and the zygomatic bodies were advanced some distance anteriorly to the standard surgical unit. The distances between the landmarks were between 5.4 mm and 16.1 mm (Appendix 3). The index of mismatch had a magnitudeof 4.2 mm (1.8 mm to the right, 3.5 mm anteriorly and 1.4 mm superiorly). There appeared to be a discrepancy due to the significant change in shape of the surgical units so that matching was not as complete as it might otherwise be.

Page 462 Crouzon Syntlrome a) versus

AI' Lateral

From Abovc Oblique

b) versus

AP Lateral

From Above Oblique

c) versus

AP Lateral

From Above Oblique

Figure 4.9 Comparison of Surgical Units for Extended Fronto-Orbital Advance in Patient LW.

4.4.4.3 Summary of the Surgical Findings for Patient LW

The pre-operative position of the surgical unit of Patient LW was relatively similar to the position of the standard. Clinically, the relatively normal anterior position of the supra-orbital ridge was demonstrated medially (Figure 3.5), with a more pronounced deficiency seen in the lateral orbital wall. The lateral orbital wall of Patient LW lies at the level of, or just posterior to, the lateral orbital wall of the standard (Figure 4.9a).In this situation, proptosis may have been a result of reduced orbital volume rather than due to deficient anterior growth of the bony orbital rim. At surgery, advancement of the fronto-orbital bar with osteotomy and overcorrection of the lateral elements, was performed.

Plate fixation was also used in this patient, but appeared to have held the lateral elements advanced at the expense of the medial part of the supra-orbital ridge. While the lateral orbital wall and body of the zygomas were brought forward during surgery, the post-operative position demonstrates they were also swung outwards. This resulted in the effect of widening thefacewitha "less than optimal" result. There are 2 ways to prevent this. Firstly, advancing the zygomatic bodies and lateral orbital walls to the same degree as the supra-orbital ridge would lessen this effect. Alternatively, when the zygomatic bodies are advanced forward they are brought medially as well as anteriorly. Resection of part of the supra-orbital bar and a medial translocation of the zygomatic bodies would readily accommodate this manoeuvre.

4.4.5 Analysis of the Pre- and Post-operative Morphology of Patient HC

4.4.5.1 Alignment of the Cranial Base Unit for Patient HC

The cranial base angle of Patient HC was more obtuse than the standard and had the effect of raising the position of the anterior craniofacial skeleton relative to the standard (Figure 4.5).

The pre-operative position of the basion lay anterior to the standard cranial base position. The obtuse cranial base resulted in even fuither superior movement of the nasion.

Chapter 4 Pctge 465 4.4.5.2 Comparison of the Surgical Units for Patient HC

Pre-operative Surgical unit vs standard Surgicat unit (Figure 4.10a)

The pre-operative surgical unit lay superior to the standard. It also lay in a significantly posterior position and accounted for the class III occlusion in this patient. Measurements varied greatly from 7.6 mm to 27.9 mm (Appendix 3). The index of mismatch between the pre- operative and standard surgical units had a magnitude of 17.3 mm and this was made up of displacement of the pre-operative surgical unit 2.1 mm to the left, 12.4 mm posteriorly and

11.9 mm superiorly, relative to the surgical standard.

Pre-operative Surgical Unit vs Post-operative Surgical Unit (Figure 4.10b)

Significant advancement of the post-operative surgical unit compared with the pre-operative unit was found (best demonstrated in the lateral and superior views). Of note, the lateral view of the surgical shift produced images similar to the cephalometric analyses readily derived from plain radiographic data. Measurements of the surgical advance ranged from 12.6 mm to 22.t mm

(Appendix 3). The index of mismatch was 16.5 mm and was made up of a displacement of 2.3 mm to the left, 15.9 mm anteriorly and 4.0 mm superiorly.

Post-operative Surgical Unit vs Standard Surgical Unit (Figure 4.10c)

The position of the post-operative surgical unit was again distorted by the effect of the cranial base alignment causing it to be positioned superior to the standard. At the occlusal level, the distances between the surgical units were shorter than at the level of the superior orbital ridge.

Lengthening of the anterior face during surgery would account for this. The lengthening may be intentional to assist the occlusal relationship, or may be the inadvertent result of surgical osteotomies and manipulation. Measurements made between corresponding landmarks ranged from 8.7 mm to 31.1 mm (Appendix 3). The index of mismatch had a magnitude of i7 .2 mm and consisted predominantly of a superior displacement of the post-operative surgical unit of

15.7 mm with displacement 3.2mmanterior and6.4 mm to the left.

Page 466 Crr,¡uzon Syndrome a) versus

AP 0bliclue Later¿rl From Ahove

b) versus

AP Oblir¡ue L¿rtcral Fronr Abovc

c) versus

AI' Oblique l,¿rteral F'ronr Above

Figure 4.10 Comparison of Surgical Units for Fronto-Facial Advance in Patient HC.

4.4.5.3 Summary of the Surgical Findings for Patient HC

Analysis of the data relevant to the fronto-facial advance, in this patient, provided information in 3 main areas. Firstly, variation in the cranial base angle altered the positioning of the anterior craniofacial skeleton. In anterior translocation orthognathic surgery this effect persists in the post-operative and standard surgical unit comparisons. Secondly, the surgical shift was well demonstrated using this method with graphic pictures showing anterior displacement.

Measurement analysis of the occlusal relationship had not been performed but was seen on the clinical images and CT scans (Figure 3.7). The final feature to emerge was the increase in the facial height which can be appreciated on the wire frame images. Variation from the standard surgical unit ¿t the supra-orbital ridge level was greater than the variation at the occlusal level and this was due to the increase in facial height. Given the premorbid increased facial heights in most patients with Crouzon syndrome this surgical alteration should be considered unfavourable relative to the standard.

4.5 Discussion of the Surgical Analysis

Analysis of the comparisons in 3D between the pre-operative, post-operative and standard surgical units in the patients undergoing corrective surgery of Crouzon syndrome demonstrated many new features relevant to the underlying pathology, the type of surgery performed and the effectiveness of this surgery with respect to overall patient appearance (Table 4.2 - 4.4).

4.5.1 Features of Pathology in Crouzon Syndrome determined from Comparison of Pre-operative and Standard Surgical Units

The cranial base was described by Enlow (1975) as the template for the face. Numerous studies have associated the cranial base abnormality with the craniofacial abnormality in Crouzon syndrome (Bennett, 1967: Rosen and'Whitaker, 1984). Pathology of the cranial base was demonstrated in cephalometric examinations (Rune et al., 1979; Kreiborg, 1981) and 3D CT scans (Kreiborg et al., 1993) and is more fully described in Chapter 3.

In this study the cranial base angle piayed an important role in determining the position of the surgical unit. When the cranial base angle was increased, the surgical unit was in a superior

Chapter 4 Page 469 position, compared with the more nonnal or inferior position of the surgical unit, when the

cranial base angle is decreased (Table 4.2, Figure 4.5). This finding highlighted the extent of

the pathology involving the cranial base. The widespread involvement of the craniofacial

skeleton in the pathology of Crouzon syndrome precluded the identification of any normal

reference points to allow a direct comparison with normal points on a standard model.

It could be argued that alternative points should be included and others deleted. Any variable

points selected would have had an effect on the alignment position of the surgical unit due to

their intrinsic pathological position. In this study, alarge number of widely spaced cranial base

landmarks were selected as the cranial base unit for alignment.

In the main, the sizes of the pre- and post-operative surgical units compared with the standards

were increased. In the patients with the mild to moderate deformity, the "shape" of the fronto-

orbital region was relatively normal. Its size and position varied greatly between patients. This

becomes relevant when surgical manipulations altered the shape during the fronto-orbital

advance procedure. There was very little asymmetry seen.

Table 4.2 Cornparison of Pre-operative and standard surgical units

PATIENT SH JS IP LW HC

Age at CT scan 5mo 2l mo 2l mo 5'5 yrs 15 yrs

Cranial base angle smaller normal larger smaller larger

Surgical unit - Size normal normal much larger slightly larger normal

- Shape good good distorted slightly good, slightly superiorly broad laterally nanow anteriorly

- Position left left right right left (mean translation (2.e) (0.2) (2.e) (0.5) (2.r) of patient relative to standard (mm)) postenor postenor very postenor posterior very postenor' (0.3) (4.3) (r2.2) (1.3) (t2.4)

inferior supenor very supenor inferior very supenor (l1.4) (2.1) (21.0) (0.7) (r r.e)

Page 470 Crouzon Syndrome 4.5.2 Results of Surgery in Crouzon Syndrome determined from Comparison of Pre-operative and Post-operative Surgical Units

At operation, several factors may have altered the result as measured in this analysis. The age at

which the post-operative CT scan was performed was significantly more important in the infant population due to the rapid bony growth of the calvaria. The results of Patient RN were

strongly influenced by this phenomenon with the pre-operative scan taken at 1 month and the post-operative scan at 10 months. The results for this patient were therefore excluded.

Reshaping the fronto-orbital bar by swinging the lateral elements anteriorly, following a medial

osteotomy,hadtheeffectof flatteningthe supra-orbital bar and producing a square appearance

to the fronto-orbital region. This surgical procedure was performed with the intention of

providing increased coverage for the globes. The effect of this reshaping was seen when

examining the position of the post-operative surgical unit compared with the standard (Section

4.5.3). When considering the effect on the directional shifts of the surgical unit, the reshaping

increased the lateral distances shifted compared with the midline. In the summary table (Table

4.3) the mean distances of the directional shifts are recorded.

Bonyfixationwaswithwirein2patientsand plates in the other 3. In general, wire fixation is

preferred in the young to maximise the floating forehead principal (Marchac and Renier , 1919). The use of plates in young patients has been a subject of controversy due to the inward

migration of plates with growth (Munro, 1993). Plate and screw fixation is more rigid and

particulariy useful for orthognathic work. It may contribute to the stability of the peri-orbital

surgical shift, particularly when anchoring 3 points such as the temporal region to the lateral

orbital rim bilaterally and at the nasal bones medially. In this small group of patients, plate

fixation resulted in a reduced surgical shift superiorly with a preference for an anterior

maintenance of position. (Table 4.3; Patients JS and LW.) The long term effects of the plates

and the positions of fixation are unknown.

The precise positioning of the surgical unit at the time of surgery, rather than the type of

fixation performed, may be equally relevant. This analysis was not able to address this issue,

although this data suggested that this might be an area of further study. Similarly, the effects of

soft tissue closure on the bony position have not been determined.

Chapter 4 Page 471 Table 4.3 Comparison of Pre-operative and Post-operative Surgical Units

PATIENT SH JS IP LW HC

Surgery FOA FOA FOA Extended FFA FOA

Reshaping of Yes Yes Yes Yes Yes lateral bar

Method of bony wue plates wre plates plates fixation

Age at post-op 8mo 22 mo 22 mo. 6 yrs 15 yrs CT scan

Surgical unit right right left right left (mean translation (1.5) (0.7) (3.8) (0.8) (2.3) of pre-operative to post-operative - anterior anterior anterior anterior anterior position (mm)) (3.3) (10.0) ( l8.l ) (5.3) (15.e)

supenor supenor supenor supenor supenor (7 .6) (3.0) ( 13.0) (3.0) (4.0)

4.5.3 Residual Deformity in Crouzon Syndrome determined from Comparison of Post-operative and Standard Surgical Units

The results of surgery, as demonstrated by the comparison of the post-operative surgical unit with the standard surgical unit, revealed 3 main features. In each patient, the size of the surgical

unit was essentially unchanged. Secondly, the shape of the surgical unit was altered by the swingof thelateral wings anteriorly. This had the effect of providing further coverage for the orbits as can be seen in the figures of the wire frame diagrams of the patients' skulls (Figures

4.6 - 4.I0). The manoeuvre changed the shape of the fronto-orbital bar away from the normal standard. Based on this limited data, consideration should be given to advancing the lateral orbital walls and/or zygomatic bodies to the same degree as the rest of the supra-orbital ridge in order to lessen this effect. Alternatively, they may be brought medially following osteotomy, as well as forward, to reduce lateral splaying of the lateral orbital wall.

Thirdly, as demonstrated in the surgical directional shift measurements, all the landmarks of the post-operative surgical units lay anterior to the standard with minor asymmetry. The position of the supra-orbital bar was generally superior, in patients where the cranial base angle was

Page 472 Crouzon Synclrome decreased. When wire fixation was used (Patient SH), the surgical shift placed the supra-orbital bar in a position at the level of the normal experimental standard (Table 4.4 andFigwe 4.7).

Table 4.4 Comparison of Post-operative and Standard Surgical Units

PATIENT SH JS IP LW HC Surgical unit - Size increased slightly greatly increased normal increased increased

- Shape broad slightly less more broad slightly broader Iaterally broad laterally distorted laterally laterally

Position right right left right left (mean translation (3.1) (0.7) (0 6) (1.8) (6.4) of patient relatiye to standard (mm)) anterior antenor antenor antenor antenor (e.3) (6.s) (7.5) (3.5) (3.2)

supenor supenor supenor supenor supenor (0.r) (4.2) (32.8) (1.4) ( l5 .7)

In summary, the present study used the cranial base for alignment to enable assessment of the region undergoing surgery. Not only the relative size of the pre-operative surgical unit, but its shape and position in space, were determined from the 3D CT analysis. The shape, size and position of the surgical unit following the surgical shift have also been assessed. The comparison of the post-operative position with the experimental standard data was performed in the early post-operative phase. At this stage, an improvement in the position of the surgical unit has been demonstrated.

Based on the trends identified in this study, a new set of questions may be asked, challenging the current surgical techniques to produce a reconstruction which is individualised for each patient's variable pathology, accurate in its execution with an appropriate method of fixation and with limited morbidity.

Chapter 4 Page 473 Page 474 Crouzon Syndrome CHAPTER 5

DISCUSSION AND SUMMARY OF MAJOR FINDINGS

5.1 The Clinical and Radiographic Features of a Population with Crouzon Syndrome

This thesis has contributed to the understanding of the variation and severity of the clinical manifestations of Crouzon syndrome by the analysis of the clinical and radiographic pathoiogy and the natural history and treatment of a population of 59 patients.

Crouzon syndrome is clasically described as having fusion of the calvarial sutures, shallow orbits with proptosis and maxillary hypoplasia leading to a class III malocclusion, all with variable severity. These findings and others in this population are summarised in Table 2.21.

Many are similar to those described by Kreiborg (1981) in the only other large population studied, such as variation in head shape, suture patency and copperbeaten appearance.

New findings from this study were a birth prevalence of 24.2 per million which was higher than other studies of 15,5 per million (Martinez-Frias et al., 1991) and 16.5 per million (Cohen and Kreiborg, L992). Seventy-five percent of patients presenting represented new mutations of

Crouzon syndrome whtle 257o had a positive family history. The new mutation rate is much higher than other studies (567o in Kreiborg's series (1981)) and while increased paternal age may be a factor the exact cause of this is not clear.

For the first time CT examination of the central nervous system of a large population of patients witlr Crouzon syndrome was reviewed and revealed a high rate of ventriculomegaly, a distortion and dilation of the ventricles which is not necessarily a functional problem. This was considered mild in 5I7o of patients, moderate in lIVo and severe with functional significance in

97o of patients (Proudman et al., 1995). Schizencephaly in one patient was a finding not previously reported in Crouzon syndrome. These findings differ from Apert syndrome central nervous system findings (Cohen and Kreiborg, 1990) where structural abnormality of brain matter and mental retardation is more common and further confirm the difference between these two syndromes.

Ophthalmological review confirmed the well established findings of proptosis, strabismus,

optic atrophy, exposure keratitis, decreased acuity, nystagmus and coloboma of the iris. In

addition, ophthalmological findings not usually associated with Crouzon syndrome were found

such as orbital dystopia in I07o of patients and ptosis in l4%o.

The findings by Kreiborg (1981) of abnormality of the ear, stenosis or atresia of the external

ear canal with middle ear disease and hearing loss were confirmed, however only 1 palatal

deformity (bifid uvula) was found in this population compared with up to l\Vo in other studies

(Kreiborg, 1981). Occlusal abnormalities were also examined confirming the established high

incidence of class III occlusion.

For the.first time in a large population with Crouzon syndrome, examination of the speech

highlighted the high rates of articulation disorder (907o), hyponasality (887o) and hypernasality

(I07o). Abnormality of the nasopharyngeal airway was manifest in the extreme by obligatory

moutlr breathing in 38Vo of patients, similar to the findings of Kreiborg (1981). In addition,

oxygen desaturation was recorded in 8Vo of patients and may be of significance in infants where

it may not be detected. Further detailed longitudinal studies of the airway in all Crouzon patients

will provide the necessary data on which appropriate treatment may be based.

Investigation of non-craniofacial features of Crouzon syndrome confirmed cervical spine

fusions, predominantly in the upper cervical spine (C-2,3) compared with Apert syndrome in

the lower cervical spine (Kreiborg, 1987; Hemmer et al., 1987). Stylohyoid ligament

calcification, elbow stiffness with radius subluxation and ankylosis were also seen in this

study. Minor hand abnormaiity was found in IOTo of patients, a finding rarely reported before

(Garcin et al., 1932; Kaler et al., 1982).

The surgical intervention in this population with Crouzon syndrome was also recorded (Section

2.4.10) and documents the indications, types of procedures, secondary procedures and complications. This follows the regimens outlined by Tessier and others (Tessier, I9JIa,

L97lb, Davidetal., 1982). All patients survived surgery. At this stage, [æ Fort III osteotomy

Page 476 Crouzon Syndrome in childhood is justifred for medical reasons. Further investigation will determine whether it

should be routinely implemented for psycho-social reasons.

Four patients of the 59 patients studied died. One suffered atlantoaxial subluxation with spinal cord compression and 3 infants with severe deformity died from respiratory difficulties.

This population data collected represents a large addition to the body of information of the

natural history and treannent of the condition. These data are consistent with the concept that

Crouzon syndrome is a dysplastic condition which affects chondral and bone growth. The

condition shows great variation in presentation. This may be related to the timing of, and

possibly the rate of synchondrosis and synostosis. The late onset of the calvarial deformity and

the early onset of the maxillary involvement seen in some patients support this concept. The

gradual onser of the cervical spine fusion, elbow deformity and stylohyoid calcification suggest

that the dysplastic bony condition is progressive. What directs the synchondrosis is not clear.

Crouzon syndrome shares many features with other cmniostenotic conditions. It would seem

that while they each have a distinct genetic pattern, and possibly pathological processes at the

level of the bone and cartilage, the resultant structural abnormalities produce similar functional

and aesthetic problems.

The concept of a primary abnormality of bone and cartilage development producing all the

features is a valid hypothesis. Some evidence does suggest, however, the CNS and the soft

tissues of the face and palate may also be primarily affected. The genetic and embryological

implications of this are not readily apparent.

5.2 The Three Dimensional Quantitative Analysis of the Craniofacial Morphology of Crouzon Syndrome

Developments in CT imaging and analysis enabled the va¡iable and complex clinical

presentation of this disorder to be defined by detailed measurement of the craniofacial skeleton

(Abbott, 1988). 3D CT reconstructions of I patients with Crouzon syndrome were analysed

using Persona 3D medical imaging and anaiysis software. Landmarks representing each

craniofacial bone were identified, allowing measurement of distances, dimensions and angles

for each bone (anatomical units). The measurements were compared with age-matched

Chapter 5 Page 477 experimental data and statistically significant regions of deformity were identif,red in each patient. This study enabled, for the first time, the identification of patterns of deformity for each craniofacial bone in Crouzon syndrome. The results should be reviewed in light of the small number and varying age of the patients studied. These new findings are sulrrnarised here.

This study identified a typical pattern of deformity of the mandible with increased gonial angle and increased symphyseal height. An increased gonial angle supported Kreiborg's findings of a tendency to an increase in the angle (1981). In addition to the typical findings it was found that the position of the condyles of the mandible could also be disto¡ted by deformity of the cranial base. Localised overgrowth at the gonial angles was also identified in one patient.

The maxilla in Crouzon syndrome is clinically described as hypoplastic, however in this study the maxilla was hypoplastic only in its anterior-posterior dimensions, and increased in its height and width. This finding was more common in the older patients and is in contrast to the findings of others (Kreiborg, 1981). This increased height and width was identified in the interorbital region, a site usually considered to be broad due to downward displacement of the ethmoid bone. CT examination and measurement clearly identified the maxilla and its atltrurÌl encroaching into the interorbital region.

The nasal bones tended to be increased in length and angled inferiorly, which was consistent

with the length and facial form of the maxilla and mandible.

Prior studies have focussed on the calvarial dimensions of the frontal bone which was not

measured in this study. In this study the supraorbital ridge, ethmoid and sphenoid attachments

have been quantified for the first time. The frontal bone supraorbital ridge was increased in

width in the majority of patients. The frontal ethmoid attachment length varied geatly and was

related to deformity in the surrounding bones. An increase in the frontal ethmoid attachment

length appeared to be related to increased dimensions of the cribriform plate. The overall clinical

deformity in the patients with a normal frontal ethmoid junction was less severe. A greater

degree of pathology in the region of the sphenoid bone was found in those patients with

reduction in the length of the frontal ethmoid attachment (Section 3.5.8 Sphenoid bone). The

superior orbital fissure was commonly reduced in length.

Page4TB CrouzonSyndrome Deficiency of the lateral orbital wall has been described and related to the posterior position of

the zygomatic bone due to fusion of the squamous and temporal calvarial sutures (Kreiborg and

Bjork, 1982)'Theinvolvementof suture fusion and the resulting pattern of the bone has been

further described in this study as presenting with minimal involvement (1 patient) or as one of 2

distinct patterns. The fronto-zygomatic pattem was characterised by suture lengthening

producing a normal or slightly wide zygomatic bone. The spheno-zygomatic pattern, a more

severe deformity with lengthening of the suture, produced a decrease in length but increase in

height of the zygomatic bone.

The vomerine bone has not previously been considered in isolation but as part of the deveioping

nasal capsule. In this study the vomer was often smaller and angled inferiorly, particularly in

the older patients, consistent with downward growth at the expense of anterior growth of the

lacial skeleton and supports the previously held concepts of the development of this bone.

Deformity of the ethmoid bone in Crouzon syndrome has classically been described as broad

with depression of the cribriform plate (Bertelsen, 1958). In this study the ethmoid bone was

examined by region and again demonstrated variable patterïs of deformity. The size of the

lateral ethmoid plate was normal in some patients but more often was reduced in size.

Involvement of the spheno-ethmoid synchondrosis has been suggested by other authors (Burdi

etal., 1986). This study was able to confirm this in some but not all patients. The posterior

ethmoid was increased in width at the spheno-ethmoid synchondrosis in half the patients, but

normal or reduced in width in the other half, producing a wedge shaped bone in the latter

group. The frontal ethmoid atcachment was reported with the frontal bone (see above). The cribriform plate was broad and the medial ethmoid plate was normal or increased in size.

The sphenoid bone has been well described qualitatively from cephalometric radiographs and

3D CT reconstructions (Kreiborg, 1981;Kreiborg et al., 1993).In this study, the sphenoid bone was again divided into regions. Severity of abnormality of the sphenoid bone correlated with the degree of clinical severity of Crouzon syndrome. In cases with mild clinical involverncnt the lesser wing showed a rnoderate deformity with pronrinent anterior clinoids arrd normal or reduced length of the lesser wing. The more severely involved patients showed a reduced size of the anterior clinoid and increased length of the lesser wing. The pterygoid plates

Chapter 5 Page 479 were generally normal in size and position. An increased lateral and posterior angle of the

pterygoid plate was identified in those patients with more severe clinical deformity and may

influence the position and projection of the maxilla. The greater wing of the sphenoid was

angled laterally. Lengthening of the spheno-zygomatic and spheno-temporal sutures was

commonly identified, consistent with fusion as described by Kreiborg and Bjork (1982). The

measurements of the sphenoid body were larger in size than the experimental standard in most

cases. This finding was consistent with raised intracranial pressure causing endocranial

resorption of the sella turcica and distortion of the lateral walls and confirmed the qualitative

findings of Kreiborg et al. (1993). The spheno-occipital synchondrosis was distorted in shape

(increased height with normal width or normal height with reduced width) but the significance

of this finding remains unclear.

There is little information in the literature about the detailed pathology of the temporal bone in

Crouzon syndrome. The temporal bone in patients with Crouzon syndrome has been described

as lrypoplastic (Nager and de Reynier, 1948). Fusion of the squamous temporal sutures has been reported (Kreiborg and Bjork, 1982).In this study several new findings emerged. The

shape of the external auditory meatus of the temporal bone was distorted. The zygomatic process was often reduced in length with an increased height of the afticular fossa. The jugular foramen was narrowed with lengthening of the surrounding cranial base sutures. One patient with atresia of the external auditory meatus exhibited a similar pattern to the other patients but with reduced measurements implying a degree of hypoplasia of the petrous temporal bone.

The parietal bone and squamous temporal bone were not analysed fully in this study, while limited measurements of the remaining basal occipiøl bone showed minimal additional abnormality.

The major cranial base sutures were measured for the first time to determine what, if any,

pattern emerged. While the pattern of suture involvement was variable, the sutures were

lengthened primarily anteriorly and laterally. Suture lengthening may imply suture fusion with

grorvthalongthelineof the suture, not always matching the involvement seen clinically in the

calvaria but allowing a suture profile to be determined for each patient.

Page 480 Crouzon Syndrome The craniofacial dimensions and angles confirmed the increase in facial height with a reduction in the maxillary projection anteriorly. The cranial base angles were quite variable, consistent with previous studies (Kreiborg, 1981) and confirmed that the morphology of this region reflects both primary and secondary forces.

From the data generated from this study and based on the theories previously postulated

(Virchow, 1851; Moss, 1959; Kreiborg, 1981) craniofacial morphology in Crouzon syndrome is due to a combination of primary and secondary pathological events. The craniofacial bones have a primary developmental abnormality with premature suture fusion of variable severity that becomes manifest with time. As with the variable calvarial shapes in Crouzon syndrome, different regions of the craniofacial bones are affected, producing the patterns of deformity in these bones described above. Moqphology of these bones is secondarily affected by 3 factors: the deformity in adjacent growing bones, raised intracranial pressure causing endocranial bone resorption and the effect of the functional matrix on the occlusion (Figure 3.41).

5.3 The Three Dimensional Quantitative Analysis of the Morphology before and after Surgery in Crouzon Syndrome

Three-dimensional measurement studies of surgical manoeuvres in infants and children with

Crouzon syndrome are infrequent in the literature. Previous studies of cephalometric radiographs (Kreiborg, 1981; Kreiborg and Aduss, 1986) and dry skull examinations

(Kreiborg and Bjork, 1982; Burdi et al., 1986) demonstrated the pathology in the fronto-orbital and zygomatic regions. Carr et al. (1992) made CT scan-based measurements of the cranial orbital zygomatic region in unoperated Crouzon and Apert infants. A detailed description of the craniofacial pathology in patients with Crouzon syndrome is reported in Chapter 3 of this manuscript. Attempts at measurement of forehead morphology was performed by Friede et al.

(1986) using digitised cephalometric radiographs.

A more recent study by Posnick et al. (1993) examined 14 measurements in 14 patients with

Crouzon syndrome who underwent surgery. The measurements were all in the cranio-orbito- zygornatic region and were measured by callipers from 2D axial CT scan images. No analysis of cranial base pathology was incorporated in the study. The findings suggested that whilst

Cho¡tter 5 Page 48) anterior movement of landmarks was performed, the post-operative measurements at one year were still significantly abnormal.

3D CT reconstructions of 5 patients with Crouzon syndrome undergoing fronto-orbital or fronto-facial surgery were extensively analysed. The fronto-orbital bar and Læ Fort III components (surgical units) were analysed using Persona 3D medical imaging and analysis software.

The position of the pre-operative and post-operative surgical units were compared with each other and with age-matched experimental standard data. This was performed by alignment of the surgical units using cranial base landmarks not in the operative field, and least squares and repeated median methodg to measure the distances between the surgical units. The severity of the pathology, the effect of the surgical manipulation and the residual deformity were all examined

The effect of the cranial base pathology on the alignment of the pre-operative and standard surgical units demonstrated that the pathology in Crouzon syndrome extended throughout the craniofacial skeleton. In general, the pre-operative surgical units were posterior to the experimental standard. The superior or inferior relationship of the pre-operative surgical unit to the standard surgical unit was related to changes in the cranial base angle.

Assessment of the surgery to the pre-operative surgical unit demonstrated an anterior translocation in allpatients. However, several new findings emerged from the analysis. When this anterior translocation was small, it was at the expense of superior translocation of the post- operative surgical unit. The degree of superior displacement of the post-operative surgical unit varied, occurring with both wire and plate fixation and may have been related to the effects of soft tissue closure.

In addition, reshaping of the fronto-orbital bar with increased lateral orbital advancement to assist in globe projection, accentuated the broad and flattened appearance of the forehead which may not be desirable aesthetically. Fronto-facial surgery however, in adults, resulted in a more reliable anterior translocation of the bones, but with a slight increase in the facial height.

Page 482 Crouzon Synclrome Further analysis is required to determine the degree and rate of relapse. Posnick et al. (1993) do not comment on possible factors influencing the degree of relapse. Extended population studies, possibly in the form of controlled trials, may help unravel this multifactorial dilemma.

In conclusion, this study correlates cranial base position with that of the surgical unit and vividly demonstrates that surgery in Crouzon syndrome (and other craniosynostosis syndromes) is a surgery of the facial facade. Variables affecting the facial surgery and which may be manipulated, are osteotomy of the lateral orbital walls, the 3D positioning of the bone, the method of fixation and the tightness of skin closure. A more complete analysis of a large population of pre- and post-operative patients with Crouzon syndrome would help define these variables further as well as the patterns of deformity in both operated and unoperated patients.

5.4 Scope for Further Studies

The analysis of 3D CT reconstructions of other populations with Crouzon syndrome would help to confirm or add to the patterns of deformity found in this study. The analysis of the craniofacial skeleton of other craniofacial deformities using this method, including a comparison with Crouzon syndrome would provide additional information on the range of craniofacial deformity. Further collection of data for the experimental standard would provide more information about the craniofacial skeleton of the normal population and enable greater statistical power for comparison studies.

Specific studies which could be addressed in Crouzon syndrome include structural, growth and surgical analyses. Regions of structural abnormality of interest not addressed in detail in this study include the dimensions of the optic foramen, calvarial abnormalities and occlusal relationships. Further measurement of the spheno-occipital synchondrosis and temporal bones may help define the dysmorphology of these regions. Narrow slice CT data would be needed for close examination of some of these areas.

Growth studies in Crouzon syndrome, by the collection and analysis of serial CT scans, would produce fr:rther information on primary developmental changes in Crouzon syridrorne as r,¿ell as on growth following surgery. Parallel detailed growtli studies of the normal population could also theoretically be undertaken.

Chapter 5 Page 483 The assessment of surgical intervention could also be extended. Using the analysis as a pre-

operative assessment of the individual patient deformity, surgery could be tailored to the sites of

pathology identified. The results of this surgical intervention could then be analysed.

The present investigation has demonstrated the detailed clinical and radiographic features of the

craniofacial morphology of Crouzon syndrome. Quantification from 3D CT reconstructions provides a greater understanding of the pathological morphology and enables analysis of the effects of surgical manipulation. This detailed analysis of the pathology and present day

surgical management of Crouzon syndrome expands our current understanding and provides the framework for future developments in this field.

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Page498 CrouzonSyndrome Appendix 1

Accuracy of Landmark Identification

Double Determinations of the landma¡ks were performed for:

I Crouzon Syndrome Population (n=8)

Pooled landmark relocation srror = 1.3 mms Median landmark relocation error = 1.0 mms Minimum = 0.4 mms for sphenion t left Maximum = 5.3 mms for vertex 2 Sample of Dried Skull Population (n=10)

Pooled landrn¿uk relocation srror = 1.2 mms Median landmark relocation error = 0.9 mms Minimurn = 0.3 mms lor crista galli Maximum = 2.8 mms for sphenion t left Appendix 1 Accuracy of Landmark Identifïcation:

Crouzon Syndrome Patients:

Landmark Rclocation Lanclmark n x v z lxvzl

alare left 8 0.5 0.9 0.9 1.4 alare right 8 0.3 0.6 0.4 0.8 anterior clinoid lefi 8 0.4 0.3 0.8 0.9

anterior clinoid righL IJ 0.3 0.3 0.8 0.8 anterior nasal spine 8 0.3 0.3 0.4 0.6

arúcuia r eminence left IJ 0.4 ol 03 0.8 articular emirence right 8 0.3 0.4 0l 0.6

arlicular fossa left 8 06 I TJ.J t2

articular fossa righr IJ 0.4 0.6 0.4 0.8 asterion in¡ìer lefl 2 0 0.4 03 0.5 asterion inner right 2 0.4 0 0.6 o.1 asterion left 2 0 0.8 0.3 0.8 asterion right a 0 0.4 0.6 o.1

auriculare lefr 8 0.3 0.9 0.5 1.1

auriculare right 8 n') 0.9 0.5 I

basion 8 06 0.4 l.t 1.3 bregma 1.8 1.6 0.5 )<

canine inferius left .5 0-2 0.4 0.3 0.5 canire inferius righr ) o2 0.2 0.2 0.4 canine superius left 6 0.4 a2 0.3 0.5 canine superius right 6 03 0.4 0.5 o1 condylion laterale lefi ti 0,3 0.3 0.5 o.1 condylion laterale righL 8 0.2 0.3 0.5 0.6

coronoid base left 8 0.6 0.6 0.6 1.1

coronoid base right 0.1 0.5 ll 1.4 coronoid tip left 04 0.3 0l 0.5 coronoid tip right o4 0.6 0.3 0.8 cribrilorm plate anterius left 8 1.4 o1 o.l t.7 cribriform plate anterius right 8 0.7 0.1 o.1 t.2 cribriform plate posterius lefi I 0.3 01 0.5 0.9

cribrifonn plate posterius right 8 03 0.4 0.8 1 crisra galli l 0.1 0.3 0.5 0.6 disto-molare inferius left 6 0.4 0.6 0.3 0.8 disto-molare inferiu s right 6 0.5 0.4 0.6 0.9 disto-molare superius left 6 05 0.5 0.4 0.8 disto-molare superius right 6 05 0.3 0.8 I ecto-cauine inferius left 8 0.6 04 03 0.8

ecto-canine inferius right 8 0.1 0.3 08 I ecto-canine superius left 8 04 0.5 0.9 l.l eclo-canine superius right I 0.9 0.7 0.9 1.4 ecto-ircision central interius lefr ti 0.2 0.5 I t.z ccto-incision central inferius righL 03 o7 09 t.2 ecto-incision central superius left 03 0.6 08 I ecto-incision central superius right 8 o4 0.6 0l I cctomolare lsL Llferius lefL tÌ 0.1 0.5 0.1 0.9 ectornolare I sL inferius righr 8 0.4 0..5 0.6 0.9

I'age ii Crouzon Synd.rome Appendix 1 Accuracy of Landmark ldentification:

Crouzon Syndrome Patients (continued):

Landmark Relocation Error Landmark n x v z lxvzl eclomolare 1st superius [efL 0.5 0.8 o.1 1.2 ectomolare lsr superius right 0.7 0.8 0.8 1.3 ethmoid spine 0.4 o;7 0.3 0.8 eu ryion left 0 t5 0.6 1.6 euryion righr 0.1 0.8 0.6 I cxtemal auditory rncatus antcrius lclt I 03 0.1 1.2 extemal auditor¡, rnoatus anterius right ll 08 0.5 1.5 extemal auditorl, lneaLus inferius left 0.1 09 0.1 1.3 extemal audirory meatus inferius righL l.l 0.5 I 1.6 extemal auditory rìleatus poslerius left l5 0.3 0.7 t.6 external auditory rneatus ¡rosterius right l.l 04 0.1 t.4 ext aud meatus sr.rperius (ie porion) L 01 0.1 0.3 1.1 ext aud n'lætus superius (ie porion) [l 0.7 0.5 0.1 0.9 foramen caecum 0.3 03 0.5 0.6 foramen in ovale lefi 0.7 0.5 0.5 I forârnen in ovalc right 0.6 09 0.6 1.3 foramen in spirosum left 0.2 03 o.4 0.5 forarnen in spìnosur.rr right l.l 0.8 o.7 1.6 foramen magnum lateralis left 0 0.5 0.5 0;t foramen mâgnurn laLeralis right 0.3 0.5 o.4 o;7 foramen ouL ovale lcft 05 05 1 1.2 foramcn out ovale righL 0.6 0.5 0.6 0.9 foramen out spinosum lolt 0.3 06 0.9 1.1 foramen out spinosurn right 0.8 0,5 I t.4 glabeÌla 0..5 0.3 0.4 0-1 gnaLhion o.1 03 0.3 0.8 gonion left 0.3 0.4 0.5 0.7 gorúon right o.2 05 oo I greater palatine forarnen lclt 08 0.5 0.9 t.-1 greater palatine forarnen righL t2 04 1.2 1.1 greater wing laterale lelt o.4 04 0.3 0.6 greater wing laterale right 0.5 01 0.8 1.2 greater wing medjale left 03 0.5 o.1 0.9 greater wing mediale right 0.1 04 o.4 0.9 harnular notch lefL 0.4 05 0.4 0.8 hamular noLch rìght 0.3 0.5 0.3 o.7 hamular process lelt 0.5 0.4 0.4 0.1 hamular process righL 0.6 04 0.8 1.1 honn ion 03 07 0.4 0.8 incision üll-erius lclt 0.3 0.4 0.2 0.5 i¡rcision mtènus nghL o.4 02 0.2 0.5 incrsron superius lcft 0.5 o4 0.6 0.9 incision superius ri ght 0.3 0.4 0.5 o.1 inferior naso-maxiÌlarc lel L o.2 0.4 o;l 0.8 inferior nasornaxillarc righL 0.(r 08 l.l 1.5 infcrior orbiLal fissLrre lcft 0.3 0.4 0.6 0.8 inferior orbital Iissurc right 0l 07 0.4 l1

Appendix I Page ur Appendix 1 Accuracy of Landmark Identification

Crouzon Syndrome Patients (continued):

Landnrark Rclocation Error Landmark n x v z lxvzl

infero-lateral orbitale left 8 0.5 04 0.5 0.8 infero-Iateral orbitale right 8 I 0.3 0.6 t.2 infradentale 8 o.4 0.5 U.J o.7 infra-orl¡ital foramen inferior left 2 0.8 0.4 0.8 t.2 infra-orbiral foramen inferior righL 2 0.4 0.8 0.3 0.9 infra-orbital foranlen laLeral IefL 2 0.8 1.9 0.3 2 infra-<¡rbital forameu laLeral righr 2 0.8 1.5 ll 2.t infra-orbital foramen left z 0.3 0.2 0.3 0.5

infra-orbital foramen medial lefi 2 o4 0.8 0.5 I

infra-orbiLal foranren medial righL 2 0.4 0.4 0.9 I infra-orbiral foramen right 2 0.2 04 0.4 0.6 infra-orbital foramcn superior left 2 04 0.5 08 I infra-orbital forame¡r superior righr 2 o4 0.4 0l 0.5 intemal auditory mearus lefr 8 0.4 04 0.4 o.7 intemal auditory meatus right 8 o1 0.3 0.6 I

intemal occipital protuberance 8 1.5 13 0.5 2.1 jugular foramen lateralis lefr 8 0.3 0.7 06 0.9 jugular foramen lateralis righr I o4 0.8 o4 I jugular foramen medial lefi 8 l3 1l 0.8 1.8 jugular foramen medial right ¡ì o.4 tl 0,6 1.3 jugular foramen posterius left 8 o1 0.9 o1 1.3 jugular foramen posterius right I l5 0.7 I 1.9 lambda a 0.1 0.4 08 0.9 lambda inner ) 0.5 12 0.7 1.4

lateral orbitale left 8 0.8 0.4 01 1.1 lateral orbitale right 8 03 0.3 o1 0.8 laLero-frontale left 6 0.9 3t 2 3.8 latero-frontale right 6 l4 2.1 22 3.5 mandibular canal left 1 0.3 04 0.3 0.6 mandibular canal right 7 0.3 0.2 o.2 0.4 mandibular notch lefr I 03 0.6 03 0.8 mandibular notch righl 0.3 0.6 o2 0.7

mastoidale lefi 0.4 09 05 1.1

masroidale right I l.l 04 1.5 maxillare superius left I 05 0.9 1.3 1.6

maxillare superius righL 8 0.3 Q] Q1 I

rnaxillary tuberosity left 0.6 09 z- r 2.3 maxillaq/ tuberosity right 8 08 0.6 l6 r.9 rnedial orbitale left 0.4 09 07 1.2 nredial orbitale righL I 0.4 0.7 l.l t.4 lnedio-molare I sr inferius lefl 6 o2 0.4 0.3 06

r¡edio-molare lsL infenus righr 6 0.4 0.3 09 I medio-molare lsr superius left 6 0.4 0.4 06 0.8 medio-molare lst superius righr 6 0.4 03 0.ó 0.8 rncnlal f<¡ranlen left 0 0.5 06 0.8 mental foramen right 3 o.4 0.4 0.2 0.6 nasalc 03 03 04 0.6

Page iv Crouzon Appendix 1 Accuracy of Landmark Identification:

Crouzon Syndrome Patients (continued):

Landmark Rclocation Error Landmark n x v z lxvzl naslon 0.2 0.6 0.6 0.9 naso-lacrimal inferius lefL 0.6 04 0.9 1.1 naso-lacrimal inferius right I 0.8 1.6 2 odontoid 0.1 o.2 0.7 0;7 opisthion 0.4 0.4 t.2 1,3 opisthocranion 0.3 0.1 0.5 0.6 optic foramen a irlcrior left 0.5 04 0.1 0.9 optic forarnen a irrferior rìght 0.3 0.3 o.4 0.6 optic foramen a lateral lefL 01 o.7 o1 r.z optic foramen a lateral right 0.8 05 05 l.l optìc foramen a lelt 0.4 0.3 0.5 0.6 optic foramen a medial left 0.3 06 0.5 0.9 optic foranen a medial righL 0.4 0.8 0.2 0.9 optic foramen a right 0.2 o.4 0.3 0.5 optic foramcn a superior lcft 0.5 L'O 0.3 0.8 optic foramen a superior right 05 0.6 0.6 I optic forâmen p inlcrior [cl"t 0.8 0.9 I 1.6 optic foramen p inferior right 0.9 0.9 1 1.6 optic foramen p lateral left 0.6 1 1.1 1.6 optic foramen p laLeral right 04 0;1 0.8 l.l optic foramen p [e[t 0.3 0.5 0.8 I optic foramen p medial lefi 0.6 0.6 0.9 1.2 oplic forarnen p rnedial r.ight 0.5 0.9 I t.4 optic foramen p right 0.3 0.4 0.7 0.9 optic foramen p supcrior lclt 0.6 0.6 0.7 1.1 optic foramen p supcrìor right 0.2 03 0.5 0.6 orbitale lefL l3 0.3 0.3 1.4 orbitale right 0l 03 0.3 0.8 petrous posterius left 0.6 1.4 04 1.6 petrous posterius right 0.7 0.9 1.8 2.1 petrous sup-anterius lclt 0.1 0.3 0.3 0.8 petrous sr.lp-anterius righL 0.3 0.5 0.3 0.1 pogoruon 05 0.4 0.6 0.9 posterìor clinoid lefi 0.-5 0.5 0.5 0.9 posterior clinoid righL 0.5 0.6 0.4 0.9 posterior nasal spine 0.3 0.3 0.3 0.5 pre-articulare left 0.3 I 0.3 l.l pre-aliculare right 0.3 0.9 0.5 1.1 prosthiorr 0.4 0.8 0.1 1.2 pterygo-[ateralis lelt 0.3 o.4 0.5 0.7 pterygo-laLcralis right 03 0.5 0.5 0.1 pterygo-superius Icl'i 0.9 06 0.5 1.2 pterygo-superius righr 0.9 o.1 0.1 t.4 sella 0.5 0.5 0.9 1.1 sphenion c lefi 0.5 0.5 0.1 1 sphenion c right 0.8 08 0.1 1.3 sphemon t lefL 0.4 0 0.1 0.4

Appendix I Page v Appendix I Accuracy of Landmark Identification:

Crouzon Syndrome Patients (continued):

Landmark Rclocation Error Landlnark x z lxyrl

a sphenion t right 0.8 0.8 I 1.5 sphenoidale anterior left 8 0.1 0.5 0.6 l.l sphenoidale anterior right I 07 0.3 t.3 r.5

srylomastoid foramen left 5 1.2 1.5 0.5 2

stylomastoid foramen right 5 0.1 0.5 0.7 0.8 subspinale 8 0.4 0.5 0.7 0.9 superior naso-maxillare left. 8 0.4 05 0.6 0.9 superior nasornaxillare right 8 0.4 04 06 0.8

superior orbiLal fissure left {J 0.1 0.5 01 l.l superior orbital fissure right tt 0.6 t2 04 l5 superior orbitale left ¡i I 0.5 o.4 1.2

superior orbiLale right 8 0.5 07 0.4 I

supero-Iateral orbirale lefi IJ 0.1 o4 06 o.7

supero-lateral orbitale righL IJ 0.3 0.6 0.5 0.8 supero-lateral orbitale superius lelt t 0.1 1.6 0.1 t.1

superolateral orbitale su¡rerius right .J 0.3 0.8 t.4 1.6 supero-medial orbìrale lef¡ 4 2.3 oo a 3.2 supero-rnedial orbiLale righL 4 )o 1.4 2.t 3.8

s uprarnentale l 0.6 0.6 0.5 I verLex 5 t.2 5.2 0.6 5.3

vomo-ethmoid inferius 8 o.2 t.4 1.9 vomo-ethmoid superius 8 05 1 0.8 1.4 zygion lefi I 0 06 0.4 0.7 zygion rìghL 8 o.2 0.8 0.5 0.9 zygo-frontale left 8 0.3 0.4 0.6 0.8 zygo-fronrale right 8 0.3 04 1.2 13

zygo-fronLaIe sphenoidale Iefi I o4 o.4 0.9 1.1 zygo-frontale sphenoidale right 8 o.4 0.4 0.9 l.t

zygo-frontale superius left -t 1.2 1.5 0.8 2.1

zygo-f ronLale superius righr 3 0 I 0.9 1.4

z¡,go-rnaxrllare infèrius latcrale lef L 0.1 05 0.4 0.6 zygo-maxillare inferius laterale righr 2.2 0 0.1 23

zygo-maxilla re inferiu s left 8 0.7 0.9 0.6 1.3 zy¡1o-maxiìlare rnferius righL 8 ll 0.1 0.5 t4 zygo-temporale left 0.2 0.8 0rJ l.l zygo-temporale righr 8 0.3 0.3 0.3 0.6

Page vi Crouzon Appendix 1 Accuracy of Landmark Identification:

Dried Skulls:

Landmark Rclocation Error Landmark n x v z lxyzl alare left l0 0.3 0.4 0.8 I alare right l0 0.3 0.3 0.6 o;l anterior cünoid left l0 0.4 0.3 0.8 I anterior clinoid righL 10 03 o.4 0.5 o;l anterior nasal spine l0 03 o.2 0.4 0.5 articular eminence lcft l0 0.6 0.6 0.3 0.9 anicular eminence righL l0 0.8 o.7 o.2 I articular fossa left 10 0.8 0.7 0.4 1.1 articular fossa righL 10 o.4 05 0.3 o.1 asterion úrner left t0 o7 1.2 t.2 1.8 asterion inner right l0 0.6 1.2 21 2.5 asterion left t0 0.1 0.9 1 1.5 asLerion right l0 0.1 1.2 2.1 2.5 aurioulare left l0 o.2 15 0.4 1.5 auriculare right l0 o.4 1.4 0.6 1.6 basion l0 0.2 0.3 0.5 0.6 bregma 8 0.5 2.1 0.5 2.8 canine inferius left 1 0.3 0.4 0.6 0.8 canine inferius righL 5 0.3 0.6 0.4 0.8 canine superius left 8 03 03 o.4 0.5 canine superius right 8 0.3 0.4 0.3 0.6 condylion laterale left 10 o2 0.3 0.5 0.6 condylion laterale right l0 0.2 0.3 o.4 0.5 coronoid base le[L l0 0.2 0.3 o.1 0.8 coronoid base righL l0 0.9 0.7 0.9 1.4 coronoìd tip left 10 o.2 o.7 o.2 0.8 coronoid Lip righL t0 0.3 o2 0.1 0.8 cribrifon¡ plate ântcrius lcft 10 0.1 t.4 1.1 r.9 cribrifonn plate anterius rìght l0 0.8 l3 1.3 2 cribrifonn plare postcnus left l0 0.5 I 0.4 r.2 cribrifonr plate posterius right t0 0.7 l.l 0.5 1.4 crista galli l0 o.2 o.2 o) 0.3 disLo-molare inferius [efL 6 04 0.5 0.6 0.8 disLo-molare inferius right 6 0.7 o1 t.l 1.5 distorloìare superius le[L 1 0.5 05 o.4 0.8 distor¡olare superius righL 1 0.3 04 0.3 0.6 ecto-cani¡e inferius lef t l0 0.4 0.5 0.5 0.8 ecto-canine inferius right l0 0..5 0.6 0.6 I ecto-canine superius lelt l0 (/.J 0.3 0.5 0.1 ecto-canine superius right l0 0.6 0.5 06 I ccto-incisiorr central ilrferius left 10 0.4 0.6 1 t.2 ecto-incision central inferius right 10 0.3 0.6 1 t.2 ecto-incision central superiLrs left 10 0.8 0.3 0.1 1.1 ecto-incision centraì supcrius righL l0 0.5 0.5 I 1.3 ectomolare I st inferius lof L l0 0.5 0.3 0.4 0.7 ectornolare I sL inferius right t0 0..5 0.3 0.5 0.8 ectomolare I st superius lefi l0 0.3 05 0.4 0.1

Appendix 1 Page vii Appendix 1 Accuracy of Landmark ldentification:

Dried Skulls (continued)

Landnlark Rclocatlon Error Landmark n x v '¿ xt7,

ectomolare lst superius right 10 0.4 0.7 0.1 t.l ethmoid spine 10 0.4 0.6 0.3 0.8

euryion left 9 o.4 0.8 1.3 1.6

euryion right 9 o.4 0.6 t 2.1 cxtemal auditory meatus anterius left l0 0.4 04 0'7 0.9 cxtemal auditory meatus antcrius right l0 0.3 0.4 0.8 0.9

extemal auditory meatus inferius leJL t0 1.t 0.4 05 1.2 extemal audirory meatus inferius righL l0 0;l 04 o4 0.9

cxtemal auditory meatus posterius lcft l0 0.9 03 0.7 1.2

extcnìal auditory meatus ¡xrsteriLrs right l0 0.1 05 I 1.4 ext aud meatus superius (ie porion) I- l0 I 0.4 0.2 1.r cxt aud rneatus superius (ie porion) Iì l0 0.8 03 0.2 0.9 foramen caecu¡n t0 0.4 0.4 o.4 0;l foranren in ovale left l0 0.3 03 0.5 0;t foramen in ovale right l0 0.4 03 0.3 0.6 foramen in spinosum left l0 1.1 t.2 0.5 t.l foramen in spinosum right l0 0.9 04 0.4 Ll foramen magnum lateralis left l0 0 0.3 o.'l 0.8 foramen magnum lateralis righr l0 0 o.2 0.5 0.5 foramen ouL ovale left l0 0.3 0.5 0.2 0.6 foramcn out ovale right l0 0.4 0.5 0.5 0.8

forarnen out spinosum left l0 1.3 1l 1 1.9 foramen out spinosum right 10 06 t2 o.1 1.5 glabella l0 04 0.2 o4 0.6 gnathion l0 0.6 0.5 0.3 0.9

gorúon lefi t0 o2 lt 0.8 1.4 gonion righL t0 0.4 1.2 09 1.6 greater palatine foramen left l0 0.3 o2 04 0.5 greater palatine foramen right l0 0.3 0.ó 0.7 I Sreater wing laterale left l0 0.4 0.3 o.2 0.5 grcatOr wing lateraÌc righL l0 0.3 0.3 03 0.5

greatcr wing rlediale left l0 06 o.4 I 1.3

greater wiilg rnediale right l0 0.6 05 t.z 1.4 hamular notch left l0 0.3 0.5 0.4 0;l hamular noLch right l0 05 0.5 0.1 o.1 hamular process left IO 0.5 05 0.3 o.1 harnular process righr l0 0.3 0.2 o4 0.6 hormion 10 0.2 0.5 0;l 0-9 incision inferius left t0 o.4 05 05 0.8

incision inferius right ti 0.4 02 0.1 0.8 ircision superius lefi 9 03 0.3 0.3 0.5 incision superius righr 9 0.4 0.3 0.2 0.6 inferior naso-maxillare lelt l0 0.6 o.4 0.9 l.l inferior naso-maxillare right l0 0.4 0.4 0.4 0.7

inferior orbital fissure left l0 0.5 o.1 0.2 0.9 inferior orbital fissure right l0 0.3 0.2 0.1 0.4 infero-lareral orbitalc left l0 0.1 o.1 o;l 1.2

Page viii Crouzon Syndrome Appendix 1 Accuracy of Landmark Identification:

Dried Skulls (continued):

Landmark Rclocation Error Landmark n x v z lxyzl inferolateral orbitale right l0 0.8 0.8 0.8 1.4 infradenrale l0 0.3 o.2 0.5 0.1 inf¡a-orbital foramen inferior lefL 6 0.6 0.3 I 1.2 infra-orbital foramen inferior righL 6 o.4 0.3 0.6 0.8 infra-orbi¡al foramen latcral lelt 6 0.5 0.4 0.5 0.8 infra-orbiLaÌ foramen lateral right 6 0.6 0.5 0.8 l l infra-orbital forantcn lefL 10 0.2 01 0.4 0.5 infra-orbital foramcn medial lefr 6 0.5 0.7 0.6 1.1 infra-orbital foramcn medial right 6 o.4 06 0.5 0.8 infra-orbital foranren righL l0 íJ2 0.3 03 0.5 infra-<¡rbiral foramen superior lelt 6 05 0.2 0.3 0.6 infra-orbital foramcn superior righr 6 o.4 0.3 0.5 0.1 intemal audiroq, meatus left l0 0.3 03 0 04 intemal auditory mcatus right l0 0.5 0.3 0.3 0;7 intemal occipital protuberance l0 t.4 0.8 0.6 t.1 jugular foramen latcralis lefi l0 0.1 0.3 0.2 0.4 jugular foramen lateralis righL l0 04 0.3 0.4 o1 jugular foramen medial lefr l0 l.l 0.7 1 1.7 jugular foramen medial righr 10 09 0.2 0.8 t.2 jugular foramen posterius [e[t l0 0.3 o.2 0.6 0.1 jugular foramen postcriLrs right 10 0.5 0.2 0 0.5 lambda 10 t.2 0.5 t.3 1.8 lambda inner l0 08 05 1.4 r.7 lateral orbitale left 10 0.2 0.8 1.6 1.8 lateral orbitale right 10 0.4 0.6 1 2.1 latero-frontale left 9 0.6 2.t 1.1 2.4 latero-frontale right 9 0.8 1.1 l.l 1) mandibular canal left l0 o.2 0.3 0.4 0.6 mandibular canal rìght l0 02 0.3 0.3 0.5 mandibular notch le.[t l0 o.2 o4 o.2 0.5 nrandibular notch right 't0 0.3 0.6 0.2 0;7 nrastoidalc lelt l0 0.6 ll 0.4 13 masroidale right l0 1.3 0.5 0.6 1.5 maxillare superius lelL l0 0.8 I o.4 l3 maxillarc supcrius right l0 01 05 0.4 I maxillary tuberosity lclt l0 05 0.6 0.6 I maxillary tuberosity righr t0 0.8 0.8 0.5 1.3 medial orbitale le[L l0 0.2 0.6 0.'l I medial orbitale right l0 o.4 0.4 1.t 1.2 medio-molarc lst inferius lefr 6 0.9 0.3 0.3 I medio-nrolare 1st inferius right 6 02 o.4 oo I medio-molarc I st superius lcft 1 o.4 0.3 0.5 o.7 mediornolare lst superius right 1 0.2 0.2 0.3 0.4 mental foramen lett 9 o.4 0.5 0.4 0.8 menLal foramen right 9 0.5 03 0.3 0.7 nasale l0 0.6 03 0.4 0.1 n âslon t0 0.3 o2 0.8 08

Appendix I Page u Appendix 1 Accuracy of Landmark Identification:

Dried Skulls (continued):

Landmark Rclocation Error Landmark n x v z xyTt

naso-lacrimal inferius lefi l0 0.4 0.6 0.4 0.8 naso-lacrimal inferius right l0 0.8 0.5 o.4 I opist}rion l0 o.4 0.3 n'l 0.9

opisthocranion 9 0.6 0.2 0.1 1 opúc foramen a inferior left l0 0.3 0.1 0.6 oa optic foramcn a inferior right l0 0.5 o.4 0.4 0;7 optic foramen a lateral left l0 0.8 0.5 o.4 t.l optic forarnen a lateral righL t0 0.5 05 0.6 0.9 optic foramen a left l0 0.2 0.3 ì) 0.4 optic foramen a medial lefi l0 I 0.1 0.3 t2 opúc foramcn a medial right l0 (r.-J 0.6 03 0.8 opric foramen a right l0 03 0.3 0.3 0.5 <.lptic loramcn a superior lefL l0 0.3 07 o.2 0.8 opLic fbrarnen a superior right t0 0.6 0.7 03 0.9 opúc foramen p inferior left 10 0.6 o.2 02 o1 optic foramen p inferior righL l0 1.2 0.3 0.5 1.4 opúc forameu p laLeral left l0 0.5 09 0ó t.2 oplic foramen p laLeral right t0 0.7 1.5 0.4 t.1 optic foramen p lcft t0 0.2 Q.4 0.3 0.5 optic foramen p medial left l0 0.6 l.l o7 1.4

optic foramen p medial right l0 09 I 0.5 1.4 optic foramen p right l0 0.5 0.5 0.3 0.8 optic foramen p superior left l0 05 0.ó 0.3 0.9

optic foramen p superior rigbt t0 0.4 0.9 0.6 1.2 orbitale lefi l0 0.1 0.4 0.3 0.9 orbitale right 10 0.8 o4 o.2 I petrous posterius left l0 0.5 2 0.9 2.2 peLrous posLerius right l0 0.5 1.4 l.l 1.8 petrous sup-anterius left l0 0.3 09 0.3 I petrous sup-anterius right l0 0.4 0.5 0.5 0.8 PoSonron l0 o.4 o.2 08 0.9 posterior cli¡loid left l0 0.5 03 03 0.7 posterior clinoid righL IO 05 05 05 0.9 posterior nasal spine l0 0-5 0.1 0,6 i.l pre-articuÌare le[t t0 0.3 I 0.2 I pre-aíiculare right l0 tJ.2 0.8 0.3 0.9 prosthion l0 0.3 0.4 0.6 0.8 pterygo-Iateral-is left l0 0.4 0.1 0.5 0.9 prerygo-lateralis righr l0 0.2 0.5 0.5 0.8 prerygo-superius left l0 12 0.8 0.3 t.5 pterygo-superius right t0 o1 0.4 0.3 0.8 sella l0 0.5 t).2 0.8 I sphenion c lefi 10 t2 t.4 tl 25 sphenion c righL t0 I I 14 a spbenion t left l0 1.5 t2 2 2.8 sphenion t right t0 01 1.4 l5 2.2 sphenoidale anterior left t0 t.7 0.3 07 1.5

Page x Crouzon Appendix 1 Accuracy of Landmark Identification:

Dried Skulls (continued):

Lantlmark Rclocation Error Landmark n x v z lxyzl sphenoidale anterior rìght l0 0.9 03 0.5 l.l stylomastoid foramen lefL 10 o.'7 0.6 0.3 0.9 sLyÌomastoid foramen right l0 1 0,9 0.3 t.3 s ubspinale 10 0.6 05 l.l 1.3 superior naso-maxillare left l0 0.8 0.5 0.1 t.2 supe.rior naso-maxillare right 10 0.5 0.3 0.8 I superior orbital fissure IefL 10 0.3 0.3 o.z 0.5 superior orbital fissure right 10 0.2 0.3 0.3 0.4 superior orbitale lclt 10 0.2 0.5 0.4 o.7 superior orbitale right l0 0.5 0.4 0.3 o.7 supero-lateral orbitale lefr 10 0.4 o4 0.5 0.8 superolateral orbitale right l0 0.3 0.4 o.4 0.6 supramentale 10 0.3 0.3 1.2 t.3 vertex 9 o.1 2.4 o.4 2.5 vomo-ethmoid inferius 10 0 0.3 o.1 o.1 vomo-ethmoid su¡ærius l0 0.4 1.6 0.5 1.8 zygion left 10 0.2 03 0.4 0.5 zygion righL l0 0.2 0.5 0.3 0.6 zygo-fronLale left l0 0.4 0.6 0.8 1.1 zygo-fronrale righL IO 0.5 0.3 0.5 08 zygo-fronLale sphenoidalc lc[L l0 1.2 'I 1.7 2.4 zygo-frontaic sphenoidalc ri ghL 10 0.9 1.2 22 2.1 zygo-maxillare infcriLrs lcl t l0 l.l 06 o.4 1.3 zygo-maxillare infcrius right l0 09 05 o.'7 1.3 zygo-temporale lelt t0 0. I o.4 0.3 0.5 zygo-Lemporale right 10 o4 0.3 0.4 0;l

Appendix I Page xi Page xii Crouzon Syndrome Appendix 2

Measurements for Dried Skull Experimental Standards

and Crouzon Syndrome Patients

I 6 Months of Age

2 2 years of Age

J 6 years of Age

4 Adult Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Months of Age:

6 Month Stanrlard Paticnt RN Patient SH

Anatomical Unit Dcfinition unit mean sd n Value Z Value Z

MANDIBLE

Dis ta n ces

L antcrior superior body id-enr I il mms l7 8 24 5 163 0 13.8 -1.61 L posterior superior body ern I il-cbl l"ms 14.3 3.9 5 t5.1 14.0 .0.08 L toral superior body id -cbl mms 30.9 5.6 6 30.6 -0 11 I -0.66 L anterior ramus cbl cLl fnrÌìs 153 2.8 6 145 -0 16.2 0.32 L anterior mandibular notch ctl-mnl rnrns 80 2l 6 9.1 7.6 -0.19 L ¡rosLerior mandibular notch rnnl-cdl ÛùllS 9.2 2.7 6 o? 0 1.6 -0.59 L posterior ramus cdl -gol ntms 22.t 6.3 6 18.7 -05 19.4 -0.43 L inferior body gol-gu tntts 40.8 6.1 6 34.6 Jð. / -0.34 R ánterior superior body id-em I ir MI¡S 18.3 1.3 5 t't I -0 15.2 -2.38 R posterior superior body ernlìr-cbr mnls t4.3 4.4 5 14'l 14.8 0.11 [ì LoLal superior body id -cbr mrns 31.2 5.4 6 30.5 -0 I 29.0 -0.41

Iì anterior ramus cl¡r-ctr nìms 15.0 4.5 6 t4.3 -0.1 1 3.8 -o.21 Iì anterior mandibular notch ctr-n'ì n r mms 8.4 2.O 6 10 I 0.8 1.2 -0.ó0

R poslerior rnandibular notch nl rr r-cd r mms 96 2.6 6 8.1 05 9.1 0.04 R poslerior ramus cclr-gor nltns 21 1 6.6 6 18.0 21.4 -0.05

R inferior body go r-8n rìì !ì ìs 39.2 69 6 34.4 -0 36.2 -0.43 I)imensio¡rs Lrtergonial dimension go[-gor mnìs 52.5 l0.l 6 42.6 -09 44.2 -0.82 LrLercondylar dimension crll -cd r nìms 66.4 93 6 63.8 58.1 -0.89 InLcrcoronoid basc dimensiotr cbl -cb r tntns 46.2 u1 6 46.0 40.3 -0.13 lnLennolar dimension ern lil-e¡n I ir ÙìÛìs 30. l 5.3 5 30.2 25.0 -0.96 [- Superior rarnus width cdl -cLl nìnìs 15.4 3.1 6 t6.4 t3.9 -0 48 I- inferior ramus width gol -cbl nìÙìs t] o 3.1 6 154 0 18.4 0.45 R supcrior ramus width c

L mandibular notch angle cdl-rnnl-ctl d"g I 18.2 14.8 6 t 28.0 131.7 0.91 R mandibular notch angle cdr-lnnr-ctr d"g I 18.5 70.o 6 l3l3 127 1 0.46 L gonial angle cdl-gol-gn d"g 121.2 5.2 6 141.8 2.8 132.0 0.92 Iì gonial angle ctl r-gor-gn d"g l3l9 21 6 145.6 136.3 1.63 L coronoid base angle ctl-cbl-id d"g 136.5 48 6 t22.1 138.6 0.44 ll coronoid base angle ctr-cb r-id d"g 134 1 5.0 6 129.6 -l 143.8 1.82 L coronoid-dental base angle ctl-cbl-ern I rl d"g 13 8.8 t.4 5 122.9 ll .3 141.9 z2t Iì coronoid-dental base angle ctr-cbr-ern I ir d.8 135 6 6.0 5 121 .2 -t 153.4 291

L symphyseal angle gol-gn -id d"g 9t.2 9t 6 89.5 -0 1 79.4 1.30 Iì symphyscal angle gor-grr -id d"B 946 44 6 89.-5 -t.l 870 t13 Anterior mandibular angle gol-gn gor d"g 't].9 5.7 6 16.2 12.2 1.00

Page xiv Crouzon Syndrome Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Months of Age (continued):

6 Month Standard Paticnt RN Patient SH

Anatomical Unit Dcfinition un¡t mcan sd n Value Z Value Z

MAXILLA I)istances Orbital Region L fronto-maxillary suture snml-morl nûls 5.8 r.ó 6 8.8 1.88 5.5 -0.19 L frontal process orbital rim nlil-morl rms 10.6 3.0 6 8.1 -0.83 8.6 -o.61 L medial orbital floor rns[-nlil mûìs 22.8 3.9 6 15.8 17.'l -1.3 I L posrerior laLeral orbital floor msl-iobfl mms 15 5 2.5 6 t2.3 -r.28 14.'l -0.32 L anterior lateral orbiral flær orl-iobll mms 123 3.5 6 I 1.0 -o.31 9.8 -o.71

L maxillary rnfra-orbital rirn od-nl i I mms 9.9 1.2 6 I r.5 1.33 9.2 -0.58 Iì fronto-maxillary suturo sntnr-lnotr nìms 6.3 1.9 6 8.0 7.5 0.63 Iì fronLal process orbiLal rirn nlir-morr mms 10.4 2.6 6 6.9 1.9 -0.96

R medial orbiral lloor lns r-n Iir ITìII1 S 22.0 3.2 6 14.3 -2.41 16.1 -1.84 lì posLenor lateral orl¡ital floor rrsr-iobfr mrns 14.5 2.3 6 t2.l -0 78 15.0 0.22 R anterior lateral orbital loor orr-iobf r mrns 12.5 3.1 6 113 -0.39 10.7 -0.58

R maxilJary infra-orbital rirn orr-n I i r mms 10.0 2.3 6 12.5 13.0 1.30 Anterior Wall L anterior zyg<.r-maxillary suture zmil-orl mms 16.6 3.3 6 1'7.6 13.4 -o.91 L lateral maxillar¡, \À,¿ll zrnil-em lsl mms 158 3.9 6 17.8 0.5 r 15.6 -0.05 L anterior alveolar margin crn I sl-pr mms 20.4 2.t 6 197 -0.33 18.1 -1. t0

L lower pyrifom margirr an s -all TTIITìS 8.1 1.6 6 10.5 8.3 0.t2 L upper pyrifonn margir all-inr¡l fnms 11.3 3.3 6 9.6 8.6 -0.82 L naso-maxillaD, suture inml-srlnl mms I1.4 2.1 6 9.3 -0.78 8.8 -0.96

R anterior zygo-maxillaq, 5¡¡¡¡s zrn I r-o rf lms 15.0 3.8 6 19.7 to.2 -t.26

R lateral maxillary wall z-rnir-em I s r ITII"IìS 176 4.3 6 19. l 0.35 16.0 -o.37

Iì anterior alveolar margin em 1 sr-pr mms 19.6 2.0 6 21.O 0 18.3 -0.65 R lower pyriform margirr ans-alr mms 9.8 2-1 6 10.4 029 11.1 0.62

R upper pyrifonl nrargin alr-inrn r mms t1.2 2.5 6 1 1.3 10.5 -0.28 L naso-maxillary suture lilrn r-st'tûì r l'mS 124 3.1 6 9.6 8.8 -1. l6

Anrerior alveolar height P r-an s mms 8.5 2.5 6 1.9 9.9 0.56 Lateral Wall

L posterior alvcolar rnargirr enr lsl-nlxLl mms t2.3 3.0 6 14. t 15.0 0.90 L posterior maxillar¡, 1v¿ll lnxLlrnsl mms 190 5.0 6 16.8 19.4 0.08 L posLerior laLeral orbjtal lkror rnsl-iobll flmìs 15.5 25 6 12.3 -t 28 t4.1 -0.32 L postenor zygo-rnaxillary suLtrrc iobfl -zrnil ûìms 10.9 1.6 6 t4.4 2.19 il.1 0.13 Iì posterjor alvcolar rnargin cl¡t I sr-mxtr flìÛìs 134 43 6 14.0 0. 14 15.3 0-44 q,¿¡¡ [ì posterior maxillar¡, rnxtr-nl s r rms 19 I 43 6 18.7 -0.09 18.4 -0.16 lì posterior latcral orbital lloor nrsr-iobfr mnts 145 236 t2.1 -0.78 15.0 o.22 R posterior z¡,go-maxillar¡, s ¡t¡¡3 iobfr- zrn ir ININS 104 1.'t 6 155 11.2 0-17 PalaLe

L posterior paÌaLal heìght crn I s[-gpl1 nìnì s 15.8 4.0 6 15.8 I 8.6 0.70

L posterior palaLal width gpl l-pns mms 9.9 t.6 6 111 0.15 l0 1 0.13 R posterior palaral height crr lsr-gplr mlns 16.8 4.9 6 15.9 ,0.18 18.0 0.24 R posterior palatal width gpir-prrs nms 99 13 6 10.6 0.54 10.4 0.38

Superior palatal len gth ân s -Pfìs mms 31.1 54 6 26.3 -0.89 )'7 A -0.59

Appendix2 Page xv Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Months of Age (continued):

6 Month Standard Paticnt RN Patient SH

Anatomical Unit Dcfinition unit mcan sd n Valuc Z Value Z

MAXILLA (continued) Dimensions

Anterior midline heighr n -pr ITìTNS 35.0 1t 6 32.1 -0.41 31.9 -o.44 L lateral height morl-em l sl mms 3 1.5 666 27.6 -0.59 26.8 -0.71 R lateral height morr-em 1sr rtlllìs 31.3 1.2 6 25.9 -0.75 26.3 -0.69 L posterior height g¡rfl -rnsl ûtJns 16 8 3.3 6 151 -o 33 t'7.6 0.24 R ¡rosterior height g¡rfrrn s r mrns t61 3.0 6 16.5 -0.07 166 -0.03 L superior length rnsl-ilml rnrns 3 1.3 56 6 24.1 -t.29 25.9 -o.96 [ì superior length nì sr-lntn r mms 31.2 5l 6 23.4 -l 53 24.4 -1.33 Posterior palatal width gpfl -gpfr mms 19. l 266 t92 0.04 18.8 -o.12 Anterior inter-canine width ccsl-ccs r INlllS 248 3.2 6 257 028 26.8 o.62 Maximurn naxillary width uttil-ztnir nìflls 60.0 9.7 6 64 1 o.42 52.1 -0;t5 Superior (inLer-orbital rirn) width orl-orr nìnìs 37.8 6.9 6 45.6 1.1 43.8 0.87 Nasal aperture heighL rìa -atìs ¡11Ûìs 14.2 236 13.8 -0. I l t.3 -t.26 Nasal apenure width a ll-a lr rnms 15. l 3.5 6 l5.l 0 15.6 0. l4 Angles

L orbital floor angle nlil¡nsl-iobfl d"g 56._5 3t 6 66.2 313 56.2 -0.10 Iì orbit¿l floor angle nli rrns r-iobfr d"g 56. I 9.0 6 151 2.11 64.5 0.93 L posterior inferior angle msl-gpfl-em I sl d"g 110.9 5.1 6 101 .3 -l I 10.3 -0.11 R posterior inferior angle rnsr-gpfr-emlsr dcg 1o9.1 6.1 6 94.4 -2.51 ll1.7 0.33 Superior maxillary splay iobfl-msl/rnsr- iobfr d"g 99.4 tt2 6 129.0 125.1 2.35 L superior /occlusal angle snml-msl/em I sl-pr deg 50.5 8.2 6 56.5 0;73 68.3 2.t] R superior /occlusal angle snmr-msr/ein I sr-pr d"g 48.8 7.2 6 577 1.24 51.9 1.26

L palatal/occlusal angle ans-pns/ern 1 sl-pr d"g 55.5 8.3 6 68. l 79.8 2.93

R palatal/occlusal angle an s -pn s/em 1 sr-pr d.g 52.8 6.9 6 63.7 1.58 '72.3 2.83

Anterior palatal angle gpfl-ans-gpfr d"g 39.3 1.9 6 42.4 1.63 3 8.0 -0.68 Maxillary arch angle gptl-prgpfr deg 40.0 1.5 6 49.0 6.00 45.8 3.87

NASAL BONES Distances

Nasal length na-n nìrns tz.2 3.0 6 12.6 0.13 13.0 o.27

L inferior nasal width na-inm I rnms 4.4 1.0 6 57 1.3 14 3.00

L nas<¡-rnaxillary suture i nrn l-s¡lr¡rl rlìnìs | 1.4 2.1 6 93 -0 1 8.8 -0.9ó T. fronto nasal suture n -snrn I illrns 5.1 0.9 6 1.8 7.6 2.78 Iì infcrk¡r nasal rvidth tìa Itìnìr nÌtìs 39 13 6 53 8.6 3.62 [ì naso-maxillary sutu re lnmr snInT mrns t2.4 3l 6 9.6 -0 8.8 - l.r6 Iì fron¡o-nasal suture n-snûìr Íìms 5.2 1.5 6 6.7 8.-5 2.20 I)imensions

hferior width irunl-ülnr rntns 1l 1.1 6 9.5 12.9 3.06 Superior width snml-srun r rnrns 8.6 2.t 6 t 0.4 10.1 0.7 r Angles

Nasal/anterior cranial base angle s-n-na d"g 100.3 8.3 6 91 .8 -0 98.1 -0. 19 Superior nasal bone angle snmì-n -srrrn r d"g I 09.8 23.5 6 90.6 -0 17.9 -1.36 Inferior nasal bone angle irurtl-na-inmr d"g 135.3 r8.5 6 119 5 -0 85 107.1 -1.52

Splay of nasal bones i rtml-snrrJ/snln r-i¡m r d.g 5.6 31.5 6 4.9 -0 18.0 0.39

Page xvi Crouzon Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Six Months of Age (continued):

6 Month Standard Paticnt RN Patient SH

Anatomical Unit Dcfinition unit mcan d n Valuc Z Valuc Z

FRONTAL Distances Supra-orbital L fronto-nasal suture n-snml ITIMS 5l 0.9 6 7.8 3.00 't.6 2.78 L fronto-maxillâry suture snml-morl lms 5.8 1.6 6 8.8 1.88 5.5 -0.19 L superior medial orbital rim r¡orl-sorl lTnls 178 3.t 6 19.0 0.39 15.4 -0.77 L supenor lateral orl¡ital rinr sorl -s lorl rnrns 22.0 4.2 6 159 -t.45 21.8 -0.05 L fronto-zygornatic sut-urc (arrLcrior) slorl -z,fl mms 4.3 05 6 4.0 -0.60 '1.6 6.60 L fronto-zygomatic suture (lateral) zll-z.lsl mns 4.9 2.O 6 4l 6.1 0.60 L fronto-zygomalic sutu re (nrediat) zfsl -si orl mms 1.1 206 3.5 1.80 10.8 1.85 R fronto-nasal suture n-snmr mms 5.2 1.5 6 6.t 8.5 2.20 '1.5 R fronto-maxillary suture sn rfì r-m orr mms 6.3 1.9 6 8.0 0.89 0.63 R superior medial orbital rim rno rr-sorr IÎJNS t] 4 2.9 6 23.4 2.O'l 9.0 -2.90 R supenor lateral orbiLal rim sorr-s lorr mms zz.8 4.O 6 16.4 -l 23.4 0.15 R fronto-zygomatic suture (anterior) slorr-z[r mrns 4.1 o.1 6 3.6 -0.71 6;l 3;71 /a R fronto-zygomatic suture (lateral) z[r-zfsr mtns 4.5 2.3 6 -0.13 4.8 0. t3 R fronto-zygomatic suture (rnediat) zfs r-slo rr ms 66 1.8 6 3.8 7.8 0.6'7 ELhmoid Nasal root projection n-fc mms 54 2.3 6 55 0.04 L fronto-ethmoid attachment (antcrior) fc-cpal mms 48 o.1 5 53 0.71 L fronto-ethmoid attachnìent cpal -c¡rpl mms 165 25 5 22.8 196 r.24 (cribriform) L fronto-eúrmoid attachrnent (posterior) cppl-ofaml mms 84 2.5 6 3.0 2.1 4.4 - 1.60 L fronto-ethmoid attachment (orbrtal) rnorl-ofaml mms 25.8 4.7 6 2t.3 ))o -o.62 [ì. fronto-ethmoid att.achment (antcrior) f'c -cpa r mms 5l t2 6 5.1 0.00 a R frorìto-ethrnoid attachnìent cpa r-c Pp r ITTjTì S t1 .6 2.9 6 23.8 19.8 0;76 (cribriform) 1 R fronto-ethmoid attachrncnt (¡rosLcrior) cpp r-ola nr r mms 8.2 2.5 6 2.9 5.6 1.04 R fronto-ethmoid attachrncnt (orbital) rnorr-o[am r mms 26.O 4.1 6 21.8 20.3 1.21 Sphenoid L superìor orbital fissure o[arnl-sobfl mms 12.5 2.9 6 11.3 -0.41 4.3 -2.83 L fronto-sphenoid suture (orbital) sobl'l-zfsl mrns t4.3 4.0 6 15;7 22.8 2.12 L lesser wing length spal-cppì r¡ms 21 .0 5.3 6 15.9 22.4 -0.87 R superior orbital fissure ofarn r-s obIr Ùìtns l l.8 2.0 6 13.1 0 5.3 -3.25

[ì fronto-sphenoid sLrture (orbital) s obIr-zfs r nms 14. I 3.1 6 16.0 05r 22.1 2.t6

Iì lesser wing lengLh s pa r-cpP r mms 25.2 4.5 6 132 25.t -0.02 Dimensions Glabellar height 8-n mms 1.6 2.6 6 61 -0.58 3.1 -t;13 Glabellar prominence s-8 mnìs 48-3 8.5 6 462 -0.25 43.5 -0.56

L anterior cranial fossa depth so rl -s pal mms 28.5 5.8 6 235 -0.86 26.9 -0.28 Iì anterior cranial lossa depth sorr-spar mms 28.O 5.2 6 284 0.08 29.4 0.21 ÂnLerior superior orbital wiclLh sorl-sorr mms 31 .4 5.0 6 504 2.û 33.0 -0.88 Anterior supero-laleral orbitaI rvidth slor.l-slor mms 68.9 10.6 6 69 -0. 19 69.'l 0.08

Posterior wid¡h spa I -spa r rnms 51 3 9.9 6 31 | -2.O4 53.6 -0.31

Appendix2 Page xvu Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Months of Age (continued):

6 Month Standrrd Paticnt RN Paticnt SH

Änatomical Unit Dcfinition unit mcan sd n Valuc Z Valuc Z

ZYGOMATC BONE Dis tances

l- zygo-nraxi.llary suture (orbital) orl-iobfI nìÌìs 12.3 3.5 6 I 1.0 9.8 -0.71 L inferior orbital fissure (ant heighQ ioblì -grv [l fNI¡S 6.9 o.1 6 45 -3.43 4.9 -2.86 L spheno-zygomatic suture zl sL-grvll mms 10.6 15 6 16.2 313 8.9 -1.13 L fronto-zygomatic suture (mcdial) zl sl-slorl rtms tt 20 6 35 -l t0.8 1.85 l- lronto z¡,goltratic suturc (atìtcrior) slorl-zli ilìilìs 43 0.5 6 4.O 1.6 660 l- fronto-z),gomaúc suture (latcral) zll t.lsl ilìtlìs 49 206 4l -0 6l 0.60 L in[cro-lateral orbiLal rirr orl-rlorl tntns 113 35 ó 94 -0.54 10.5 -023 I- infero-lateral orbital rirrr i I orl-lorl nìnìs 85 ll 6 91 109 5l -3.09 L lateral orbital rim lorì-s [orl I¡InS 3,1 1.1 6 4.0 0..53 41 094 'zll-ztl L lateral frontal process Ûìûìs 143 2.6 6 19.9 zt5 l l.0 -t 21 L zygomatico-ternporal su[ure ztl-parl nìms 12.6 37 6 r0.ti -0.56 9.0 -1.13

L inferior arch pa rl-zrnil tnms 15.8 4.6 6 8.8 r 3.8 -0.43 L zygo-maxillary suture zrnil-orl IììMS 16.6 .J..J () t] .6 0.3 13.4 -0 97 R zygo-maxillary suture (orbiral) o r-iobfr Ûìnls 125 31 6 il3 -0.3 10.7 0.58 R i¡ferior orbital fissure (ant height) iobfr-grvl r mrns 6.8 09 6 5.3 5.3 -1.61 R spheno-zygomaúc suturc zfsr grvlr rnrns ILl 2.8 6 t'7.9 243 6.9 -150 ll fronro-zygomatic sutu re (mcdial) zfs r-s lorr nìms 6.6 1.8 6 3.8 78 0.61 Iì fronto-zygomatic suture (anLcrior) slo rr-zfr tnnts 4.1 0.7 6 3.6 -0 71 6.7 3.11 lì fronto-zygomatic sutLr rc (latera l) zl r -z[ s¡ mms 4.5 2.3 6 4.2 -0 t3 4.8 0. l3 l{ rnfero-lateral orbital rim orr-ilorr nìnìs 9.6 3.8 6 10.2 01 96 000 l{ i¡fero-laLeral orbital rim i Io rr- [o rr INNìS 9.6 1.9 6 9.6 52 -232 R lateral orbiLal rim lorr slorr IIìMS 1.1 6 44 1.24 56 1.94 lì lateral frontal process zI¡-ztr [tfns 15.4 -t.-t o 19.5 124 102 -l 58 R zygomatico-Lemporal suturc 7,lt -pàr( mms 117 4.8 6 12.6 0. l9 10.4 -0.21 R inferior arch l)a rr- znr r r nìrns 15.9 53 6 8.2 145 16.5 0ll I{ zygo-maxillary sutLrre 7,lnIr- or î Ûìnls l5 0 38 6 t9.1 t.24 to2 -1.76 f)irnensions

L zygomatic height slorl -zrn i I Ûìnts 23.5 50 6 259 0 23.O -0. 10 lì zygomatic heighL slorr-znl i r [ìr'us 68.6 ll.0 6 lt I 0 63.0 -0.51 L zygornaric length pa rlorl fntns 298 64 6 252 0 1)1 -l.ll R zygomatic length Pa rr-orr nt ms 21.1 8.0 6 26.9 24.2 -0.36 L zygomarrc latcral depth gwll ilorl rnnìs I1.8 2.6 6 13.1 o73 130 o46 R zygomatic lateral depth grvlr-ilon mÌìs I 1.6 236 145 12.5 0.39

VOMER Distances

PalaLaI length an s -prì s MIIIS 3l I 5.4 6 ¿(). -t -0.89 21 .9 -0.59 Posterior choanal height pn s-h nìrns lt 8 4.4 6 88 -0 68 10.8 -0.23 Spheno-vomerine juncLion h -ves tnms 10.4 5. l 6 4.5 9.9 -0.10 juncúorr Ethmoid-vornerine \ro s - vcl nxtìs 11.4 3.9 6 t46 082 8l -0.69 Septal attachment \/et-atìs flìtts 17.8 15 6 18.0 003 zt8 0.53 Dimension and Angle

Vornerine length h ans Íìms 3 9.8 7.8 6 34.1 -0 13 3 8.0 -023 Vomerine angle s-rt/h -ans (c8 209 31 6 245 o91 t] I -l 03

Page niii Crouzon Svndronte Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Six Months of Age (continued)

6 Month Standard Paticnt RN Paticnt SH

Anatomical Unit Dcfinition unit mcân sl n Valuc Z Value Z

ETHMOID LaLeral PlaLe DisLances L anter-ior border lateral plaLe nlil-nrorl mms 106 30 6 8.1 -0.83 8.6 -0.67 L fronral ethrnoid attâchmcnL (orbital) rnorl-ofam I rnrns 25.8 4.1 6 21.3 ))o -o.62

L posterìor bordcr latcral pÌatc clf aln I -rn sl rnrns 8l 19 6 8.4 0. J. I -r.26 L illèrior bordcr lateral plaLc ¡rsl-nlil Íìms 223 3.9 6 15.8 1.19 11.1 -l 31

R anterior bordcr latcral platc n li r- rno rr nìflls I0.4 2.6 6 6.9 70 -0.96 R frontal ethmoid attachment (orbiLal) lnorr-olamr Ûìrns 260 41 6 21.8 20.3 -1.21

R posterior border lateral plate olarn r-ln s r rnrns 78 2.8 6 8.6 4.7 -1.11 Iì inferior bordcr laLcral platc msr-nlir mms 22.O 3.2 6 14.3 -2 41 r6.1 -1.84

L frontal ethrnoid attachtnent (anLcrior) rnorl -cpa I IÌilNS 4.6 0.9 5 6.1 1.9 3.67

L frontal ethtnoid attachrnent (posterior) cppl-olarn I mrns 8.4 256 3.0 2.1 4.4 -1.60 R frontal elhmoid attachnlent (anterior) rnorr-cpâ r fnrns 4.9 l.l 6 6.6 155 9.4 4.09 R frontal ethmoid attachnìent (¡nsrerior) cppr-ofarn r rnrlìs 82 25 6 2.9 2.1 5.6 - 1.04 Dimensions

Posterior inferior rvid Lh rlslln s r fntns 21.2 5.9 6 18.1 -0.53 I 8.8 -0.41 Antcrior inlerior rvidth rrli l-n [i r ilìnls 2t) 8 31 6 23.1 0.78 24.7 1.05 Anterior superior width mor[-morr mms 15.3 2.4 6 2r.1 16.9 0.61 Posterior superior width ofam [-olanr r mms 15.6 3.1 6 14.3 t5.2 -0. l3

Ant lateral projection o[ lateral plate ril i[-mor[/rnorr-n [i r d"g 31 .1 11.5 6 18.8 51.5 171 Post lateral projection ol lateral plate msl-of aml/ofarnr-msr ,leg 21 .g 12.1 6 26.8 401 1.02 Cribriform Plate l)istances L anterior cribrifonn plaLc lc c¡;al nìms 4.8 o.1 5 5.3 0.71

L lateral cribrifonn platc cpa I -cppl mrns 16 5 25 .5 22.8 2.52 19.6 t.24

I- postcrior cribrifonn 1>latc cs -cppl NìIììS 4.6 r.5 6 5.2 0.40 6.3 1.13

[ì anterior cribnfomr plate f c-cpa r mrns 5l t.2 6 5.1 0.00 R lateral cribrifonn ¡rlatc cPa r-cJ)Pr tììnìs lt6 ?O A 23.8 2t4 198 0.16 R posterior cnbrifonn plaLe cs-cPPr mrrs 4.4 1.6 6 1.0 5.2 0.50 Angles

L angle lateral cribrifonn plaLc ci SN s - n/c¡ra l-cp¡r I dcg 4.9 6.0 5 66 0.28 ')) -0.45 l{ angle lateral cribrìlonn plate cf SN .-,r7.pn r-cpf. deg 8.0 51 6 09 1.25 to -0.89 Medial anglc oi plaLc cf SN n-s/es-lc deg 64 3.2 6 6.6 0.06 Medial PlaLe

I)is ta n ces Anterior height crista galli lc-cg illms 52 2.7 6 9.4 r.56 Posterior heighL crista galli c8-cs nìrns t3 tÌ 4.4 6 13.1 -0.02 Spheno-eLhmoid rncdial pÌatc jtrrrctiorr cs -v cs nlrns 10.8 50 6 6.5 -0.86 12.0 o.z4 Ilthmoid-vornerirrc junction vcs -vcl nlms 114 3.9 6 14.6 0.82 8.1 -0.69 Ssptal âLtachûìctìt vet-t] nlnts 23 I 1.1 6 22.t -0.1 4 ))a -0.03 NasaI proicction n-lc NìINS 54 236 5.5 0.04 Dimcnsiu¡rs Maxirnum rnedial plaLc hcìght \/ct -cg [ìnìs r6.-5 1.4 6 15.0 -0.20 Maxinrum mediaL plaLc lcrrgth rì -0s mtns 25.'l 4.1 6 29.0 0.83 21.9 0.60

Appendix 2 Page nx Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Months of Age (continued):

6 Month Standard I¡aticnt RN Paticnt SH

Anatomical Unit I)cfinition unit mcÀn sd n Valuc Z Value Z

SPHENOID l-esser Wing Distances

L rnedial wirg ofaml-acl mms 8.2 l.l 6 95 I l8 9.9 1.55 L lateral wing (poscerior) acl-spal Inms 25.4 4.t 6 16.9 -2.O't 22.8 -0.63 [- lateral wing (anterior) spal-cs [ì[ìs 3l l 5.4 6 20.1 -1 93 2'7 4 -0.69 lì. rnedial rvirg of¿nrr-acr IììIII5 82 l.r 6 9.8 1.45 12.0 3.45 R laLeral wing (posterior) äcr-sPâr mnìs 23.3 4t 6 14.5 -2.15 19.8 -0.85 ll lateral wirg (anterior) sPar-cs nìrns 300 52 6 20.0 -1 92 28.3 -0.33 I)imensions

Maximum lesser wing width s pal-spa r mms 57.3 10.0 6 36.9 -2.04 54.O -0.33 Lrsser wing superior angle spal-es -spar d"g 146.1 6.5 6 129.9 150.8 0.72 L lateral projecrion (anterior anglc) n -s/acl -spa i d"g 59.4 3.1 6 49 1 54.3 - r.38 l{ lateral projection (anterior angle) n -s/acr-spar dcg 58.8 6.0 6 46.2 -2.1 61.2 r.40 Pterygoid Plate Distances L medial pterygoid plate ptsl-hpl mrns 15.1 6.0 6 12.9 12.6 -0.52

L medial hamular notch hpl -hn I mms 3.1 l.l 6 3.3 0.t 40 0.82 L lateral hamular notch hnl-ptll mllìs 6.8 10.6 6 8.7 0.1 4.3 -0.24 l- laLeral pterygoid plate pl U-fool INNS 14.3 114 6 6.6 10.4 -0.34 R medial pterygoid plaLe pLsr-hpr mms 149 5.4 6 14.4 12.6 -0.43 R ¡nedial hamu.lar notch hpr-hrrr rnfns 3.2 1.5 6 3.8 4.4 0.80 '7) R lateral hamular notch hn r-pLIr mrns 14 10.ó 6 5.1 -0.22 R lateral pterygoid plate ptl r-foor nìnìs 12.9 122 6 l0 6 -0.1 11.2 -0.r4 Angles

L pterygoid axis n -s/ptsl -hpl d"g 48.6 14.3 6 44.9 54.6 o.42 R pterygoid axis n-s/ptsr-h¡rr d"g 50. r 142 6 46.0 -o.29 55.1 035 Greater Wing Distances Lateral

L anterior rniddle cralúal lossa l osl-grv ll rnnìs L3..t 4.6 6 23.0 -0.07 25.O 0.31

L spheno-zygomatic suture zl'sl-grvll nìrns 10.6 1.5 6 t6.2 373 8.9 - 1.13 R anterior middle cranial fossa fos r-g rvl r nìms 25.l 49 6 26.1 26.1 o.20 I{ spheno-zygomatic suture g rv I r-zfs r IIìIIìS I l.l 286 t] .9 2.43 6.9 -t.50 Orbital L inferior lateral orbital length grvll-grvrnl rnrns 21.5 5.5 6 16.8 -0.85 18.0 -0.64

L superior orbital fissure height grvrn l -sobfl Ìtìr'ns 14.9 6.1 6 t3.2 -0.28 1.7 -2.t6 L spheno-frontal suture (orbiral) sobfl -zfsl tnms 14.3 4.O 6 15;l 0.35 2.12 R inferior lateral orbital length grvlr-gwrn r [ìÛìs t94 49 6 16.8 -0.53 19.8 0.08 Iì superior orbital fissure heighr g rvm r-sobfr nrtìs 15.0 4.1 6 15.0 0.00 3.3 -2.49 I{ spheno-frontal suture (orbital) s<.¡bf r z[s r nl nìs 14. I 3.1 6 16.0 0.51 22.r 216 PosIerior

L spheno-petrous temporaì suture (inÊ) fosl-pLsl tnnìs l0 5 8.7 6 8.9 -0.1 8 10.8 0.03 R spheno-petrous temporal suLure (inl) fosr-Ptsr Itìnìs tt2 8.1 6 I t.4 0.o2 12.9 0.21 I- posterior middle cranial fossa ios[-petal rntfìs 15.6 2.5 6 16.5 o.36 t3.9 -0.68

R posterior middle cranial fossa fo s r-peLa r nìms 29.1 4.3 6 3t;t 0 272 -0.58

I'age xx Crouzon Syndrotne Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Six Months of Age (continued):

6 Month Standard Paticnt RN Patient SH

Anatomical Unit Dcfinition unit mcan d n Valuc Z Valuc Z

SPHENOID (continued) Dimensions and Angles

Posterior sphenoid width fosl-fosr mms 39.2 3;7 6 40.4 o.32 34.4 - 1.30 L angle of greater wìng spla1, zfsl-gwrnl-ptsl d"g 132.5 131 6 123.O -0.69 r22.5 -0.73 R angle of greater wirìg spla), zfsr-gwmr-ptsr deg 134.4 16.9 6 125.0 -0.56 I14.5 -1.18 'foral aogle of protrusiorì zfsl-grvml/gwm r-zfsr d"g 100 4 52 6 107.3 1.33 t25.3 4.79

Inferior greater rving pltltrusiorr grvll-grvrnl/grvrnr-gwl r deg 992 6.0 6 I t0.0 1 .80 117.8 3.10

f)osterior angle ol greatcr rvirrg Ios I -peLal/peLar-fos r deg 965 12.4 6 79.O -l.41 74.8 -1.'t 5 Squamous Sphenoid

L squamous spheno-frontal sutrrre z-fsì -spcl mms 144 4.O 6 6.8 - 1.90 15.8 0.35 L squamous spheno-parietal su[urc spcl -sptl mms 82 l5 6 14.4 4.13 r 1.9 2.47 L lateral spheno-lerrporal suture fosl-spLl mrns 34.8 6.4 6 30.4 -0.69 3 1.0 -0.59 R squamous spheno-frontal suture zfs r-s pcr mlns 13.4 2.8 6 5.5 -2.82 t6.2 1.00 R squamous spheno-parietal suture spc r-sptr runs 1.8 1.6 6 20.1 8.06 9.4 1.00

R lateral spheno-Lemporal suture fosr-sptr NÙTìS 32.8 8.5 6 29.2 -0.42 32.3 -0.06 Sphenoid Body Distances Lateral/Posterior Bod¡, L anterior inferior lengLh grvml-ptsl mms 104 6.2 6 15.5 0.82 tz.4 o.32 L spheno-occipiral synchondrosis ([ar) ptsl-peLal mms t0.z 5.1 6 tt.2 0.18 10.7 0.09 L posLerior clinoid heighL petal-pcl mns 6l t.3 6 8.1 1.08 8.5 I.38 Posterior clinoid width pcl-pcr rnnìs 68 l.l 6 6.6 -0.18 10.6 3.45

Iì anrerior infenor length gwmr-ptsr ITìITìS 10.6 6.1 6 15.8 0.85 1 1.5 0.15

R spheno-occipital s¡rncþe¡¿ror;r 11ut¡ ptsr-pel,a r nùns ll4 4.9 6 10.9 -0.10 1 1.5 o.02 R posrerior cliroid heighr petâ r-Pcr mms 72 2.0 6 8.7 0.75 r0.9 1.85 Anterior Body

L spheno-ethmoid suLure es -cppl mms 46 1.5 6 5.2 0.40 63 1.13

L anterior lateral distancc cppl -ofanr I mms tÌ4 256 3.0 -2.r6 44 -1.60 L anterior supcrior length ofarnl-grvml IÎfNS 16 1.7 6 4.0 -2.12 )J -1.35 l{ spheno-ethrnoid suture cs-cpPr nìms 4.4 16 6 '1.0 1.62 5Z 0.50 Il anLerior lateral distancc cpp r-o[arn r mms 82 2.5 6 ,o -2.12 56 - 1.04 R anterior superior lengrh ofam r-gwm r rtrns 70 1.8 6 5.2 - 1.50 6l -1.00 Sella L lateral anterior bod¡, cppl-of pml Ùìms 94 22 6 6.9 -t.14 8.2 -0.55

L lareral sella length o[prnl-pctal mrns 1.5.9 38 6 15.8 -0.03 11.0 0.29 R lateral anterior body cppr-olprn r mms 10.5 25 6 1a -1.28 8.7 -0.72 R lateral sella lengLh ofprn r-pcLar mnìs 16.0 34 6 16.6 0. l8 1'7.'t 0.50 Base/Floor of Body

Spheno-ethmoid meclaI plate junction e5 -ves mnìs 10.8 5.0 6 6.5 -0.86 t2.0 0.24

Spheno-vornerin e j unction h -ves mlrs 10.4 5.1 6 4.5 -1.i6 9.9 -0.10 L posterior rvidLh h-ptsl mms I 1.3 1.1 6 r5.6 3.91 8.8 -2.21

R postenor widrh h-ptsr ITIJIìS I1.5 1.5 6 16.6 3.40 8.5 -2.00

Appendix2 Page xxr Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Months of Age (continued):

6 Month Standard Paticnt RN Paticnt SH

Anatomical Unit Dcflnition un¡t mean sd n Valuc Z Value Z

SPHENOID (continued) Dimensions

Anterior inferior body width gwml-gwmr mms 21.4 26 6 20.4 -03 19.3 -0.81

Spheno-occipital synchondrosis (in[) prsl-prsr rûns 1 9.8 26 6 2t.6 15. I -1.81 Anterior superior body width ofaml-ofarnr mms 15.6 3l 6 14.3 15.2 -0 13 Spheno-occipiral synchondrosis (sLrp) petäl-pcta r ININS 16.0 26 6 19 0 t.l 16.9 0.35

[- posterior body height pcl-pLsl ININS l5 0 40 6 16 I 144 -0. l5 R posterior body heighL pcr-pts r ININS 16 I 4t 6 t 5.9 t'| .2 0.21 L anterior body height acl-gwrnl rfìtns 8. I l0 6 9.3 70 -0.20 L anterior body heighL acr-8wnì r ttlnS 8.8 04 ó 8.7 -0.25 9.9 2.15 Angles

Body floor angle cs -v es -h deg 108.1 27.7 6 148 I 1.4'7 t05.1 -0 09 L lower body angle srr/gwml-ptsl d"g 43.7 10.7 6 34.5 0 48.6 o46 R iower body angle s-n/gwmr-ptsr d"g 154.9 3.3 6 152.5 -0.13 156.4 045 L upper body angle s-n/ofpml-petal ,l"g 21.3 4.9 6 zt.3 29.0 | 5'7 R upper body angle s -n/ofpm r-pet ar ,l"g t't.4 8.0 6 23.7 o;t9 27 1 t29

TEMPORAL

Dis ta nces Squamous

L laLeral spheno-temporal surure lbsl-sptl rnms 348 6.4 6 30.4 -o.69 3 1.0 -0.59 L temporo-parictal suture sptl-âsl rnJns 54.5 83 6 42.4 46.6 -0.95 L occipital rnastoid height asl-r¡al mms 30.0 5.1 6 26.5 28.4 -0.31 L medial mastoid prominence r¡al-slnfl rnms 6.9 1.2 6 t.5 0.50 R laLeral spheno-temporal suture [osr-s ptr rnms 328 8.5 6 tot 32.3 -0.0ó R temporo-parietal suture sptr-âsr mms 563 8.8 6 47.8 -0 48. I -0.93 Iì occipital mastoid height asr-m ar mms 32.9 3l 6 239 I 28.1 - 1.55 R medial mastoid prominence rn a r- srn fr rnms '7.1 2.8 6 7.9 0.29 Extemal Auditory Meatus (EAM)

[- lateral mastoid prominence nlal-ealnil mms 94 3.3 6 12.5 0.9 9.4 0.00 l. rrúerior-postcri<.¡r D¡\M run carnil-carnpl ililtìs 72 2.8 6 74 10.8 1.29 L posterior-superior EAM rirn earn p[-¡rl tntns 3.8 t.2 6 9'l 4 65 2.25 L superior-anrcrior EAM rim pol-eanral rnrns ?o 1.6 6 64 6.0 1.31 L anterior inl-erior EAM rim camal-eal¡l il tnms 5.7 2.4 6 1.4 0'7 1.3 0.61 R lateral mastoid prominence m â r-cänìlr mnìs 8.8 3.1 6 12.2 8.3 -0.14

R Lnferior-posLerior EAM rim caIIìl r-eaût Pr mrns 1.2 3l 6 I.-t 003 9.2 0.65 R posterior-superior EAM rim ealnp r-po Í rnms 4.1 0.6 6 8.2 6.83 5.9 3.m R superior-anrerior EAM rim POr-eamar rfMs 5. t 2:3 6 9.2 239 5.4 o.'t4 R anterior-inferior EAM nm eamar-eamlr mms 5.9 1.1 6 1.4 0.88 1.4 0.88

I'age xxii Crouzon Synd.romc Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Six Months of Age (continued):

6 Month Standard Paticnt RN Paticnt SH

Anato¡nical Unit Dclinition unit tncân tJ n Valuc Z Value Z

I'EMPOIìAL (conLinued) Zygoma L EAM-anicular Êossa length eama[-afl mms 98 )) É, to.7 0.41 a'7 -0.05 L anicular fossa height afl -ael mms 53 2.0 6 8.1 5;7 0.20 L inferior arch length ael-parl mms 5.7 2.1 6 5.8 4.O -0.63 L zygomarico-temporâl suturc parl-ztl mms 126 3.2 6 10.8 9.0 - 1.13 L superior arch length z|l-atl mms 20.3 5.2 6 10.4 10.5 -1.88 R EAM-articr¡lar fossa length eamar-afr mms 10.5 t9 6 13.4 1.53 9.3 -0.63 R articular fossur height afr-aer mms 5.4 1.4 6 9.1 4.3 -0.'79 R inferior arch lcngtlr acr-Pa rr mms 4.1 3.9 6 '/.o 0.59 4.7 0.00 R zygomaúco-temporal sutu re palr -zLt mms 11.7 4.8 6 12.6 0. l9 10.4 -o.2'7 lì superior arch ìength ZIl-àDÍ mms 19.8 5.4 6 13.4 -1.19 9.4 - 1.93 Petrous L spheno-petrous tcnrporal suturc (sup) fisl-petal truÎs 14.4 2.4 6 13.9 -o.2t 10.4 -1.61

l- post-med tenrporo-occipital suru re petal-jfpl ITITNS 22.1 3.8 6 19.3 -o.7 19.4 -0.71

L lateral temporo occipital suturc jfpl-as i I runs 28.3 57 6 28.1 0.07 30.0 0.30 L peLrous superior rnargin asi [-pctal mrns 44.8 6.8 6 41.2 -0.53 41.4 -0.50

R spheno-petrous tcrnporaI surure (sup) lis r-peta r nìms 15.3 0.9 6 14._5 -0.89 tr.2 -4.56 Iì post-rned temporo-occipiLal suLu re pcta r-j [p r mms 23.6 31 6 19.7 -1.05 21.5 -0.51

R lateral temporo-occipita I su[urc jfpr-asir Íìms 31.2 6.2 6 28.6 3 r.9 0.1 1

R petrous superior margin as r r-Pctä r mrns 46.tt 1.t 6 42.1 -0.58 44.3 -0.35

L occipiLal mastoid suture inferior rr al -j fll mms lt 6 z.l 6 1 1.9 0 15. I t.61 L jugular lorarncrl rviclth j ill -j fìn I mms 1.0 4Z 6 '74 o.2t 3.4 -0.86 L medial temporo-occipital suLure (irf) jirnl-pLsl lTìfns 17.8 6t 6 r6.7 -0.18 25.1 1.20 L spheno-pctro[rs temporal suturc (inf) iosl-pLsl nìtns 10.5 8.1 6 8.9 -0.18 10.8 0.03 R occipital mastoid su[ure ir'ìlerior nra r-jür Íìms lt.1 2.O 6 10.8 -o.45 15. I 1.70 R jugular foramen rvidth jflr-jtrnr ffIms 1.2 3.5 6 1.9 5.2 -0.5'l R medial temporo-

L petrous ridge lengLh ¡rcLal-petpl mÍìs 40.5 6.9 6 40.2 -0.04 39.9 -0.09 R petrous ridge lengLh petar-petpr mms 43.9 8.5 6 4t.6 -o.27 41.8 -0.25 lnter-ùrtenlal atrd rncatLrs dirnension iarnr-iarnl rúns 30.3 6.6 6 33.4 0.41 29.0 -0.20 Inter-extemaI arrd nteattrs dir¡rensiolr pol-por nìnìs 66.2 ll.6 6 60.8 -0.41 60.4 -0.50 Inter-post jugular foramerr dirnension jfpr-jipl mms 388 1.9 6 33. l 33.5 -0.6't

lnter-mastoid dirnension rnalrn a r rnms 56.8 13.1 6 562 -0.04 60.0 0.23 Angles Auditor¡' canal angle pol-iarnl/iarnr-por dcg 129.8 8.2 6 98.8 -3.78 t35.4 068 Petrous ridge angle pcLpl-pcLal/pctar-peLpr deg 92t 68 6 101.8 t.43 81 9 -o.62 L zygoma projection anglc pctal-aul-ztl d"g 91 .3 6.1 6 108.9 13l 9 567 lì zygoma projcction anglc pctar-aur-zLr d"g 98.8 4.8 6 I04.8 r.25 130.0 6.50

Appendtx ¿ I'aBe xxut Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Months tlf Age (continued):

6 Month Stanclard Paticnt RN Paticnt SH

Anâtom¡câl Un¡t l)cfinition unit mcan sd n Valr¡c Z Valuc Z

PARIE'I'AL Distances Sagittal surure l- br mms 0

L parietal frontal (coronal) suLurc br-spc I rrrns 0

L spheno-parietal suture spcl-sptl mms 8.2 r.5 6 14.4 4.1 1 1.9 2.41 L temporo-parietal suture spt[-asl ûìms 54.5 8.3 6 42.4 46.6 -0.95 L occipito-parietal (lambdoid) suLure asl I rnrns 61.1 13.0 6 82.9 16.0 0.68 R parietal frontal (coronal) suture br-spcr mrns 0 R spheno-parietal suture sPcr-sptr mms 7.8 1.6 6 20.1 94 1.00 R temporo-parietal suture sPtr-asr r¡ms 563 8.8 (¡ 41.8 -0 91 48. I -0.93 I{ occipito-parieLal (larnbdoid) suLure as r-l rnms 68.8 l 3.1 6 8t 3 095 80.6 0.90

OCCIPITAL Distances Lambdoid and Cranial Base

L occipito-parieral (lambdoid) suLurc | -asl rnrns 61.1 130 6 82.<) \.22 16.0 0.68 L lateral terrìporo-occipiral suLLrre (sup) a sl -j fll flìrns 26.8 4.9 6 21 .4 0.12 24.7 -0.43 [- lateral jugular foramen jfl l-jrpt nìilìs 4.8 1.8 6 2.5 -t 28 77 1.61 I- rnedial jugular foramen itpl-jfnrl rilns 5.2 4.2 6 6.0 0.l9 6.5 0.31 L medial lemporo-occipiral suLLrrc (inf) jfrn [-ptsl nwts t7.rì 6.1 6 t6.1 -0. l8 25.r t.2o R occipito-parietal (lambdoid) sururc l-asr nìms 68.8 13 I 6 8l 3 0.95 80.6 0.90 [ì lateral ternporo-occipiral sururc (sup) asr-jflr rnlns 29.5 4.3 6 21 .2 -0 -o.77 R latcral jugular Iorarncn jllr-jl pr llìnìs 4.tt 2.0 6 2.8 1.9 L55 jugular Iì. medial foramen .ifprj f m r nìms 1.5 4.O 6 6.2 -03 92 o.42 R medial lemporo-occipital suturc (ilf) jftnr-ptsr rnrns 21.3 5.2 6 16.8 -0 28.8 1.44 lnferior spheno-occipital synchondrosis pts r-ptsl rnrns I 9.8 2.6 (r 21.6 0 l5.l -1.81 Foramen Magnum

L anterior foramen magnum ba-finll nì[ts 14.1 2.4 6 14.6 o2l 14.6 o.2t posterior L foramen magnum fmll

R posterior foramen magnum fnl I r-cr rÌì¡lìs 196 3.4 6 19.7 003 21 0 0.41 Dirnensions Iìoramcn Magnurn

Foramen magnum length ba-o Ììùns 21.2 4.8 6 293 0.44 28.9 035 Foranren rnagnurn width fnr ll -lrnlr mÛts 19.6 45 6 Iu 4 -0.21 19.5 -0.02 Posterior Cranial Fossa

Posterior cranìal fossa depth o-loP n]n ts 25.5 2.8 6 15 3 -3.64 28.1 l.l4 Posterior occipiral height iop-l nìnìs 50.5 93 6 62.2 t.26 56.6 0.6ó L posterior fossa length pctpl-iop rnnìs 499 636 3 8.4 -l 83 44 1 -o.92 I- posrerior fossa length Pctpr-roP nlÌìs 41.O 61 6 53.7 t.l0 469 -0.02

Page xxiv Crouzon Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Six Months of Age (continued):

6 Month Standard Paticnt RN Paticnt SH

Anatomical Unit I)cti n ition unit mcân d n Valuc Z Valuc Z

CRANIAL BASE SU'IURI]S Anterior Cranial F-ossa

L spheno-erhmoid sl,nchondrosis es -cppl mms 4.6 1.5 6 5.2 0.40 6.3 1.13

R spheno-ethmord synchondrosis es -cpP r nìms 44 1.6 6 1.O 1.62 <) 0.50 L spheno-fronLal suture (anL fossa) cppl-spal lTLms 21 .O 5.3 6 15.9 -2.09 22.4 -0.87 R spheno-frontal suture (ant fossa) cpp r-s pa r mms 252 4.5 6 13.2 -2.6'l 25.1 -o.o2 L spheno-frontal suture (orbital) spal-zfsl mfns t2.l 3.8 6 15.6 o.92 12.3 0.05 R spheno-frontal suLure (orbital) spar-z[sr mms 119 3.4 6 18.3 1.88 16.0 t.zl

L spheno-zygornatic suture zfsl-grv I I mrns 10.6 r.5 6 16.2 3.13 8.9 -1. 13 R spheno-zygorììatic sr¡tu re zls r-g u,l r mms 1t.l 2.8 6 r79 2.43 6.9 - 1.50 Middle Cranial Fossa L spheno-squamous ternporal su[urc gwl.l-fisl ûIms 23.3 4.6 6 20-2 -0.6'7 23.3 0.00 R spheno-squarnous tem¡x>ral sutu re grvlr-fisr INNìS 23.3 4.6 6 23.2 -0.02 24.0 0. l5 L spheno-petrous tc¡lìporal strLure (sup) fìsl-petal Ìnms r4.4 2.4 6 13.9 -o.2r 10.4 -t.6'7

R spheno-¡retrous ternporâl suture (sup) I is r-peta r l.ms t5 3 0.9 6 145 -0.89 tt.2 -4.56 L spheno-petrous ternporal suture (irrl) fosl-pLsl mms 105 8.7 6 8.9 -0. 18 10.8 0.03 R spheno-petrous ternporal sutLrre (inf) losr-ptsr nìrns 11.2 8.1 6 114 0.02 129 o.2l Posterior Cranial lìossa

L medial temporo-occipital suLure (sup) petal-jfnr I ININS l6.l 3.4 6 13.5 -o;76 20.3 124 R medial temporo-occipiLal suture (sup) petar-j fm r mnìs t] 3 1.6 6 14.5 -1;15 23.4 3.8 r L mcdial temporo-occipital suture (ini) jtrnl-ptsl mrns 17.8 6.1 6 t6.1 -0.18 25.r r.20 R medial temporo-occipital sutLtrc (inf) jftn r-pLs r nìrns 21 3 5.2 6 16.8 -0.87 28.8 1.44 L occipital mastoid sutLrre (supcrior) jiLl-çretpl mnìs 25.2 3.1 6 )1 ) 0.65 24.4 -0 26 [ì occipital masloid sulrrre (superior) jfl r-peLp r ûìms ¿o..) 46 6 28.6 0.50 27.7 0.30 Spheno-occipiLal s¡,nchondrosis (sup) pctâl -pcta r rnrns 16.0 2.6 6 19.0 1. l5 r6.9 0.35

Spheno-occipital s),nchondrosis (inf) pLsl -pLsr mms 19.8 2.6 6 2t.6 0.69 15. l -1.8I <1 L sphcno-occipital s¡,nch¡¡¡¿.orit 11rt¡ pLsl-petal mrns 10.2 6 tt.2 018 10.7 0.09 R spheno-occipital s¡,nchondrosis (lat) pts r-peta r mms ll4 49 6 10.9 -0.10 I 1.5 0.02

CRANIAL BASE Facial Heights Anterior facial heighL rì-gn mÍìs 51 3 12.1 6 68.0 0.84 62.5 0.41 L posterior facial heighL s-go rnms 44.9 9.4 6 4t.9 -0.32 40.1 -0.45 Iì. posrerior facial hcighL s-8or mms 46.0 9.9 6 40.3 -0.58 42.8 -o.32 Facial Angles 't6.9 SNA srl - ss deg 823 2.9 6 1.86 1'l.4 -r.69 SNB s-tì-sItì d.g 141 226 61'7 5.64 CraniaÌ Base Anglc Cranial base anglc lra -s -n deg I 40.9 4.1 6 141.8 0.22 t24.4 -4.O2

Cranial Ilase Dirncnsi on s Cranial base lerrgth ba-lr mnìs (A5 106 6 6ó.8 0.22 61.6 -0.27 Clivus lcngth (posterior cranial base) ba -s nìrns 245 4.t 6 21 4 0.71 21.1 0.63

¿13. 'l Anterior crarrial basc lcngth s-n IIìTTì S tÌ .2 6 43.0 -0.1 I 42.0 -o.25

Appendix2 Page xxv Appendix 2 Measurements for the Experimental standards and the patients with Crouzon Syndrome:

Two Years of Age:

2 Ycar Standard Paticnt JS Patic'nt IP

Anatomical Unit Dcfinition unit mcan sd n Valuc Z Value Z

MANDIBLE Distances

L anterior superior body -em id 1i I mms 18.5 0.1 5 19.8 20.6 3.00 L posrerior superior body cm I il-cbl mms 22.8 32 5 22.8 2t.l -o.34 L total superior body -cbl id Inms 39. l 2.8 5 40.5 0 40.2 0.39 L anterior ramus ctrl -cLl ntms 16.9 2.2 5 21.5 21.2 195 I- anterior mandibular notch ct[-rnnl mms l0.ri l.l 5 8.3 13.0 2.U) L posterior mandibular notch mn [-cdl Ìùtìs 10.7 1.9 5 I 1.8 058 14.3 1.89 L posterior rarnus cdl-gol nllns 29.4 1.8 5 30.6 o.67 30.0 0.33 L inferior body gol-gn fnrns 41.8 4.6 5 50.2 50.9 o.67 R anterior superior body id-em 'j9.9 I ir rnrns 1.3 5 I8.6 20.5 0.46 R posterior superior bod¡, ern I ir-cbr mms 20.9 2.5 5 23.4 )'t 1 0.92 R toral superior body id -cbr mms 3'7.6 1.5 5 39.7 4t.5 2.ñ R anterior ramus cbr- ct r rnrns 20.4 14 5 23.1 93 19.2 -0.86 P- anterior ltìandibular notch ctr-mtìr mms il.1 1.3 s 8.6 I 1.8 0.54 l{ posterior rnandibular norch lnnr-cd r mms 12.0 1.6 5 13.1 1.06 1 3.5 0.94 R posterior ramus ,)0 cd r-gor ûùns a 15 5 30.2 0.27 31.6 t20 R inferior body gor-gtì rtms 46.9 3.4 5 516 49.8 0.85 Dimensions lntergonial climension -gor g

L mandibular notch angle cdl -nln l-ctl d"g I 16.0 1.6 5 122.5 0. lzt.8 0.16 R mandibular notch angle cd r-ln n r-ctr d"g r22.6 l1.l 5 102.2 -l 128.9 0.57 L gonial angle cdl -gol -gn d"g t29.4 52 5 130.3 0.1 134.2 0.92 R gonial angle cd r-g or-g n d"g 132.7 4.6 5 131 9 -0.1 l3 1.0 -o.37 L coronoid base angle cLl-cbl-id d"B 131.8 7.8 5 139.3 t36 5 0.60

R coronoid base angle ctr-cb i r- d d"g 132 t 6.6 5 139 3 1.09 136.2 0.62 L coronoid-denral base angle cLl-cbl-crn lil d"g t 4t.3 4.5 5 143.5 0.49 139.3 -0.44 R coronoid-dental base angle cLr-cbr-enr I ir d"B 139.5 6.0 5 146.3 I .13 140.3 0. l3 l- symphyseal angle gol-gn-id dcg 919 2.'3 5 928 0. 96.2 154

Iì symphyseal angle gor-gn i - d deg 91.7 3-6 5 90.0 -04 9'7.7 1.61 Anterior mandibular angle gol -gn-gor d.g 7 s.9 625 63.1 11.8 -0.66

Page xxvi Crouzon Syndrome Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Two Years of Age (continued):

2 Yoar Standard Paticnt.IS Patient IP

Anatomical Unit Dcfinition unit mcan d n Valuc Z Valuc Z

MAXILLA

Dis ta n ces OrbitaÌ l{egion L fronto-maxiUary suture snm[-morl mms 6.8 1.3 6 5.9 -0.69 17.4 8.15 L frontal process orbital rinr nlil-morI MS t2.t 1.5 6 tt.1 -0.27 I 1.0 -0;73 L medial orbital floor nlsl-nlil mms 24.4 226 24.5 0.05 t't.7 -3.05 L posterior lateral orbiral floor rnsl-iobll mms 16.8 1.2 6 t] .3 0.42 14.1 -) )< L anterior lateral orbiral floor orl-iobtl mrns 14.0 1.3 6 14.3 0.23 9.1 -3.77 L maxillary infra-orbiLal rinr orhrlil mlns l 1.9 21 6 t3.1 14.3 1.14 R fronto-maxillary suturc snrn r-m orf mms 5.8 o.7 6 5.3 -0.7r 17.2 t6.29 R frontal proccss orbiLal rim nlir-morr mms 12.0 0.9 6 I 1.3 0 7.4 -5.rl ll medial orbital floor msr¡rlir mms 23.5 1.9 ó 24.9 0 t7.9 -2.95 R posterior lateral orbiral floor msr-ioblr nms 16.0 1.2 6 11 0 0.83 t].0 0.83 R anterior lateral orbiral floor orr- iobfr mms 139 1.3 6 14.2 o.23 7.5 -4.92

R rnaxillary i:rfra-orbiral rinr orr-n I ir nì¡ns 12.1 1.2 6 12.4 0 r 8.4 5.20 Anterior Wall

L anterior zygo-lnaxillary suturc zrnil -o rl mms t6.8 0.8 6 18.8 2.50 22.3 6.88 L lateral nraxillar), wall zrnil-crn I sl nilrs t73 t9 6 2t2 2.O5 23.6 3.32 L anterior alveolar margin cm I sl-pr mms 21.3 1.7 6 23.2 t.1z 24.4 t.82 L lower pyrifonn rnargirr arrs-all mnts l0 I 0.9 6 109 0.89 13.7 4.00 upper pyrifonn L rnargin all-inrnl Ììrns l 3.5 1.6 6 11.4 -1.3 I 15.6 1.3 1 L naso-maxillaD, suturc in¡nl-snml mms ll.l 1.4 6 10.1 -0;t r |'t.6 4.64 ll anterior zygo-maxiLlary surure znt rf -or1 mms 16.8 t2 6 18.5 t.4z 20.5 3.08 lateral p¿[¡ Iì maxil[ar¡, zntir-crnlsr ûìms 1 tÌ.0 t.9 6 t9.0 0.53 26.3 4.37 Iì anrerior alveolar margin em lsr-pr mms zt.6 1.5 6 24.O 1.60 ))o 0.87 Iì lower pyrifonn rnargir ans-alr mms 10.5 t-4 6 9.5 -o.7r 12.5 1.43

Iì upper pyrìIonn rnargirr a I r-inr¡r r ITTI"IìS 12.5 1.2 6 11.3 15.5 2.50 L naso-maxillaO, sutu re rìrnr-srìrnr mms 12.1 1.8 6 10.4 t7.1 2.18 Anterior alveolar heighL pr-â fìs mms 9.4 2.2 6 r0.2 12.8 r.55 Lateral WaIl

L posterior alveolar margin em I slrnxtl mms l9.l 4.1 6 23.5 t.o1 17.0 -0.5 r l. posterior maxi[[ary u,all nìxtlinsl nìIns 21.1 0.8 6 t] .1 5 28.8 8.87 L posrerior lateral orbiral lloor nrsl- io l¡ ll mrns 16.8 1.2 6 ft.3 0 14.1 _) )< L posLerior zygo-maxillar), suLurc iobfl-zmrl mms 136 0.6 6 t4.3 1t7 24.'l 18.50 [ì posLerior aìveolar rnargirr ent I s rrttxtr nlrns 18 4 4.0 6 24.1 i.58 16.6 -0.45 Iì posterior maxillary wall Inxtr-nì s f nùns 21 3 Q] 6 11 .4 -5.57 29.t I 1.14 R posterior lateral orl¡iral floor rns r-iobf'r mrns r 6.0 1.2 6 17.0 0.83 17.0 0.83 R posLerior zygo-nìäxilláD, surure ioblr-z¡n ir Ûìms 133 0.9 6 l3.6 0.33 23.5 1 1.33 Pa laLe

[- posterior palaLaì hcighL enr I sl-gpfl rnms 21.0 286 ))o 0.68 18.ó -0.86 L posLerior palaLal rvidrh gpfl-pns nìr¡s t2.0 l.r 6 10.3 -1.55 r 1.9 -0.09 Iì postenor palaral hcighr cnt I ; r-gpfr rfì nl s 2t.o 296 L5.3 o.79 18.7 -0 79 lì posterior palaLal rvidrh gpfr-prrs nìrns ll4 ll 6 l1.6 0. 18 12.8 t.21 Supcrior palatal lcrrgLh arìs Pns Ilì[ìs 321 1.0 6 36.3 3.û 33.1 100

Appendix 2 Page xxvti Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Two Years of Age (continued):

2 Ycar Standartl Paticnt JS Paticnt IP

¡\natomical Unit Dcfinition unit mcan sd n Valuc Z Valuc Z

MAXILLA (continued) Dimensions

Anterior midline heighr rì -Pr mms 38.0 2't 6 39.5 0 51.1 1.O1 L lateral height morl-em 1s I mrns 34.'t 256 38.2 381 1.60 R lateral heighr morr-em l sr mms 34.1 2.4 6 387 38.2 1.46 L posterior height gpfl-nrsl mms 19 8 09 6 19.1 -0 7 25.2 6.00 R ¡rcsterior height gpfr-rn s r ININS 19.8 1.0 6 197 -0 23.3 3.50 L superior length msl-inml ININS 335 l9 6 342 28.1 -2.84 R superior length msf-lnmr mtns 33.8 1.5 6 34.1 30.0 -2.53 Posterior palataI widrh gpfl-gpfr mnìs 22.1 1.5 6 2t.t 23.3 0.40 Anterior inter-canine width ecsl-ecsr rlìms 21.8 3.5 6 31.2 0 30 I o.6 Maximum maxillary widLh zmil-z,mtr mms 62.6 4.5 6 63.9 71 .4 3.29 Superior (irter-orbital rim) width orl -<¡ rr INfNS 45.8 4.2 6 48. I 055 58.0 2.90

Nasal aperLure height na -an s mms 17.0 1.1 6 15.4 -0 22.4 3. 18 Nasal aperrure width all -alr rtms t].t 1.9 6 15.8 l 8.1 0.53 Angles

L orbital floor angle n [ilrnsl-iobfl de8 55.5 5.1 6 54.5 43.9

R orbital floor angle nli r-rn s r-ioblr d"g 57.8 6.1 6 53.3 -0 59.0 0.20 L posrerior inferior angle rlsl-gplì-ern I sl deg 107,1 100 6 116.4 0.93 100,6 -0.65 R posterior inferior angle lnsr-gpfr-enr I sr d.g 105.7 5.7 6 ll6 6 191 t07.2 0.26

Superior maxiìlary splay iobfl -rn slÁrr s r- i<¡l>lr ,l"g 105.5 9.2 6 98.1 0 94.8 - 1.16 L superior /occlusal angÌe snmJ -msl/cnr I sl-¡rr d.g 50.1 3.9 6 44.7 57.O |.62 R superior /occlusal angÌe snrnr-msr/ernlsr-pr d"g 509 4.0 6 43.9 -t.t 5 52.9 0.50 L palatal/occlusal angle arrs-pns/enr I sl-pr deg 64.0 3.8 6 54.1 -2.61 60.4 -0.95

R palaral/occlusal angle an s -pn s/eln I s r-p r d"g 58.2 4.O 6 55.0 59.9 o.43 AnLerior palatal angle gpfl -ans-gpfr deg 41.6 19 6 348 -3.58 4l .0 -0.32 Maxi-llar¡, arch angle gpfl -prgpfr d"g 4t.3 2.3 6 348 -2 83 44.1 1.48

NASAL BONES Distances Nasal length na-n mns t3.9 1.8 6 l5.8 23.5 5.33

L inferior nasal width na-inrn I ìrms 5.2 t.l 6 8.8 3-21 8.6 3.09 L naso-maxillary suture inrnl-snmì mms ll.l 1.4 6 l0.l -0 71 17.6 4.64 L fronto-nasal suture n -snnll rn¡lìs 59 1.3 6 8.6 2.08 8.9 2.3r R inferior nasal width nâ -l tìrn r mms 48 t0 6 88 8.0 3.20 R naso-maxillary suture tnmr-snmr mms 12.1 1.8 6 10.4 -o.94 11.r 2.78 R fronto-nasal suture tì -snrn r mms 69 ll 6 8.4 96 2.45 Dimensions lnferior width inmI.-inrnr IÙNS 8.3 1.6 6 12.9 287 t2.3 2.50 Superior width snml-srllr r nìrns l0 l I.5 6 r0.8 041 9.1 -o.67 Angles Nasal/anterior craniaÌ base anglc s-rì-rìâ deg 92..4 1.6 6 99.8 0.91 10.3 2.9r

Superior nasal bone angle s¡lm | -rt -s nrn r dcg 9'l t l7.l 6 79.3 -l .04 5 8.8 2.24 Inferior nasal bone angle illrnl-na-inrnr d"g 131 1 t7 1 6 93.9 -2.47 94.8 2.42

Splay of nasal bones i n l ¡r I -srr rn l/s rurr r- i nrn r dcg 95 (¡tì 6 t23 0.41 I 1.3 0.26

Page xxviii Crouzon Syndrome Appendix 2 Measurements for the Bxperimental Standards and the Patients with

Crouzon Syndrome:

Two Years of Age (continued):

2 Ycar Standard I'atiedt.lS Patlent IP

Anatomical Unit Dclinition unit mcân S n Value Z Valuc Z

FRON-I'AL Distances Supra-orbital

L fronto-nasal suture n-snml fTLITìS 59 1.3 6 8.6 8.9 2.3r L fronro-maxillaD, suture snml-morl mms 6.8 1.3 6 5.9 t7.4 8. l5 L superior medial orbital rìnr morl-sorl nìms 178 0.9 6 17.4 34.6 18.67 L superior larcral orbital rim sorl -s lorl mms 23.1 1.8 6 26.8 2'1.0 2.17 L fronto-zygonìatic suture (anterior) slorl-zfl nìrns 4.7 0.1 6 5.6 5.4 1.00 L fronro-zygomatic st¡tu re (lateral) zll-z[sl nìms 6.1 1.1 6 1.0 0. 18 14.5 4.59 L fronto-zygonratic sutu rc (rnedia l) zlsl-slorl TNIÎS 95 1.5 6 9.6 o.o'7 t6.4 4.60

R fronto-nasal sutr¡re rì -snrn r mms 69 l.l 6 8.4 1.36 9.6 2.45 [ì fronto-maxillary suture snnì r-rn or I.l]I¡S 5.8 o.1 6 5.3 -0.7 | l't.2 16.29 R superior medial orbital nnr rììo rr-sorr mms 16.8 06 6 16.1 -0.17 33.3 n.50 R supenor lateral orbital rinl sorr-s Iorr mms 23.2 l3 6 26.O 2.15 28.1 3.11

R fronto-zygornatic suture (ârìLerior) s I orr-zfr mms 5.3 l0 6 5.9 0.60 83 3.00 '7 R f ronto-zygomatic sutu rc (laLerat) ztr-z[s r mms 6.1 1.8 6 1 10.6 2.50

R fronLo-zygornatic suturc (rnedial) zls r- sl o rr mrns 8.9 t.t 6 ot 0. 18 r3.5 2.11 ELhmoid Nasal root projecLion n-fc fnms 70 1.5 6 o? 087 4.4 -2.33 L fronto-erhmoid attachrnent (anLcrior) lc-cpal fnms 6.3 t.3 6 6.5 0. 20.6 11.00 a1 L fronto-ethmoid attachlncnt cpal-cppl mfÌs 169 t.4 6 ^ 3.93 t4.5 -t.7 | (cribriform) -1.10 L fronLGethnìoid aLtachrnent (posterior) cppl -ol anr I mnìs 10.3 21 6 l9 -4.00 8.0 -1.83 L fronto-ethmoid attachmenL (orbiLal) rn orl-olarn I fnt¡s 30.7 12 6 26.5 -3.50 21.3

[ì. lronto-ethrnoid attachrrrent (antcrior) f c-cpa r nìrlls 5.9 l.l 6 6.9 0.91 20.5 t3.27 R fronto-ethlnoid attachnlenl cPa r-c[)p r INIlìS 18.3 t9 6 ))'1 232 11.1 -0.63 (cribrifom) R fronto-ethmoid attachmenL (posLerior) cpp r-o[arn r mrns 10.1 1.9 6 4.8 -2.19 8.2 -t.00 R fronto-ethmoid attachnìent (orbitat) rnorr-olam r rnms 30.8 0.5 6 26.7 -8.20 22.3 -17.00 Sphenoid

L superior orbitaI fissurc o[arnl-sobl'l rÌùÌì s 13. 1 326 t2.o -0.34 28.7 4.88 L fronro-sphenoid suture (orbital) sobfì -zfs I mms 17.5 4.2 6 18.7 o.29 15. I -0.5'l L lesser wing lengLh spal-c¡rpl lnINS 25.5 3.9 6 24.5 3 1.0 1.41 R superior orbital fissurc ofaln r-soblr fnms 10.8 4.0 6 9.0 -0.45 30.5 4.93 Iì fronto-sphcnoid suturc (orbiLal) sobl r zfsr mms t92 34 6 16.3 -0.85 tt.1 -2.21 28.3 33.7 1-13 R lesser w.ing lcngth s Pa r-cpP r mrns 26.1 44 6 Dimensions '7.6 Glabellar height 8-n ITMS rJ5 13 6 10.4 t.46 Glabellar pronri nerrcc s-g rnms 562 3.0 6 563 0.03 63.5 2.43

L anterior cranial iossa dcpLh sorl -spa I mrns 32 Íl 2.5 6 34.9 0.84 28.5 -t.12 lì anterior crartial fossa dcpth sorr-sPaf rnms 33.9 2t 6 34;7 0.38 26.1 -3.7 |

Anterior superior ortrital width s<¡rl -s o rr nìms 395 2.5 6 39 1 -0.16 62.0 9.00 Anterior supcro-latcral orbiral witlLh slorl-slorr Inms 109 40 6 't6.2 1.32 90.9 5.00 I)osterior width spal s¡rar mms 51 9 636 61.8 0. 12.2 2.2'7

Appendix2 Page xxtx Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Two Years of Age (continued):

2 Ycar Stantlard Paticnt.IS Paticnt IP

/tnatornical Unit I)cli ni tion unit mcân sd n Valuc Z Valuc Z

ZYGOMA fIC BONI]

I)is ta nces L zygo-maxillary suLure (orbital) orl-iobfl mms t4.o 1.3 6 14.3 023 9.1 -t;17 L inferior orbital fissure (ant heighL) iobtl-gwtl mms 6.9 l3 6 8l 0 16.0 7.00 L spheno-zygornaúc suture zf sl-gwll rnms 13.2 t.z 6 tz.9 -o 25 5t.-t 20.08 L fronto-zygornatic suture (rnedial) zl sl-slorl rnrìls 9.5 t5 6 9ó 007 16-4 4.û

L fronto-zygonìatic suture (antcrior) s lo rl- zfl IIìINS 41 o1 (¡ 5.6 r29 5.4 1.m L fronto-zygomatic suture (lateral) zfl-zlsI fnlns 6.1 t.1 6 10 018 14.5 4.59 [- infero-lateral orbital rim orl-ilorl Ìnms il4 08 6 13.0 1'7.2 1.25

L infero-lateral orbital rim ilorl -lorl r tìrììs 10.9 14 6 10, I -o 51 l5.l 3.00 L lateral orbital rinr lorl-slorl rnms 3.9 1.9 6 4.2 0.1 0.0 -2.05 L lareral frontal process zll-ztl [ì flls 166 1.8 6 165 21.0 578 L zygonìatico-ternporal sutu rc zLl -pa rl nì nìs 163 2.1 6 14 8 -0 7l fl.1 o.61 L inferior arch parì-zmiI rnms 72.4 1.9 6 19.2 -l 68 18.6 -2.00

L zygo-maxillary suture zrn il-orl fn tns I6.tt 0.8 6 18 8 223 6.88 [ì zygornaxillary suture (orbital) o rr-io bfr nì[ìs 139 l3 6 r42 023 1.5 -4.92 Il inferior orbital fissure (anL heighL) iobIr-gwlr nìtns 1.5 2.0 6 1.4 -0.05 t4.6 3.55 lì spheno-zygomaúc suture g rvl r- zfs r InÙìs tî a 2.2 6 t49 095 3t3 8.41

[ì fronto-zygomatic suturc (mcdial) zl sr- s Io¡r tìlIns rì.9 17 6 92 0l 13.5 2.11 R fronto-zygomatic suture (anterior) slorr-zfr mms 5.3 1.0 6 5.9 0 8.3 3.00 R fronto-zygomatjc suture (lateral) zl'¡ -zl sr rnms 6.1 18 6 71 0 106 2.50 Iì, infero-lateral orbital rim orr-iLorr Ûilns 99 l3 6 tzo I 144 346 (¡ R infero-lateral orbiLal rim i I orr- lo r¡ rnms 11.7 l.l 9.9 I 15.0 3.00 lì latcral orbital rim Iorr-sIorr IÌìINS 3ll 23 6 53 065 00 - 1.65 R lateral frorrtal proccss zÍ r-ztr tnrns t69 20 6 t] .5 0 26.5 4.80 R zygomatico-temporal suture Ltl-Pà(1 tntns n.0 2.o 6 13..5 -1.1 20;7 1.85

Iì inferior arch I)Af 1-'Ltnt Í rnrns 22.6 25 6 21.2 16.8 -2.32

R zygo-rnaxillary suture zrn I r-orr ¡lìfns 16 8 1.2 6 18.5 20.5 3.08 Dimensions

L zygomatic height slorl-z-rnil rnn'ts 26.8 09 6 21 .9 41.2 16.00

R zygomatic heighr s lorr-zrl i r INiNS 117 43 6 75.3 0 91.1 4.51

L zygomaric length pa r[-orl rn¡ns 34.3 11 6 336 0 .11 36.4 1.24 Iì zygomatic length pâfr-orr tnms 353 22 6 34.9 -0 I 34.4 -0.41 L zygornaLic lateral depth gwl[-ilorl tÌìtns 142 l5 6 15.0 053 152 0.67 L zygomatic laLeral depth grvlr-ilorr IÍìNìS 15 3 22 6 r63 045 l 1.0 - 1.95

VOMER Dis tances Palaral length ârìs-l)ns nìms 321 l0 6 36.3 3 .t.t. I 1.00 Posterior choanal height ¡rns h [ìnls 15.2 1.8 (r 14.1 -o t2.t | -12 Spheno-vorrierine junction h -vcs mms 10,9 3,0 6 I 1.4 0l l6 6 1.90 Ethmoid-vonleri.ne ju nction \/cs-\/ct nì Ins 13.6 3.6 6 t24 -03 l1 t.64 Septal attachrncnt vct-ätìs |n nìs 233 3.6 6 25.5 06r 21.8 0.42 Dimension and Angle

Vorncrìne lcrrgth Ir -arrs Itìnìs 428 23 6 462 I 43.2 0. l7 Vorncrilrc arrglc s-rr/h-ans ,l"g 20. s 25 (¡ 20r -0 36.0 6.08

Page xxx Crouzon Syndrome Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Two Years of Age (continued):

2 Ycar Standard Paticnt JS Paticnt IP

Anatomical Unit Dcfinition unit mcan d n Valuc Z Valuc Z

E'I'HMOII) LaLeral PlaLe Distances L anterior border lateraI plate nli.l-morl mms 12.1 1.5 6 tt.7 -o )'l 11.0 -0.73 L frontal ethmoid attachnrent (orbital) morl-ofaml mtns 30.1 1.2 6 2,6.5 --t 2t.3 -7.83 L posrerior border lateral plate olaml-msl mms 9.9 l.i 6 8.1 -l 4.1 -5.27 L inferior border lateral plate r¡sl-nU mms 244 2.2 6 24.5 0.05 t7.7 -3.05

R anterior border lateral plate nlir-morr mms t2.0 0.9 6 1 1.3 -0.78 1.4 -5.1 1 Iì frontal erhmoid attachment (orbital) morr-ofar¡ r mns 30.8 0.5 6 26-7 22.3 -17.00 R posterior bordcr [aLeraI plate ofam r-nl sr mlrs 10.5 11 6 7.3 -2.91 4.3 -5.64 R inferior border latcral plate rns r-n Iir lTms 23.5 19 6 24.9 0. r7.9 -2.95

L frontal ethmoicl attachnìenl (anLerior) rnorl-cpaI ITtrIì S 6.8 t.2 6 4.4 3.7 -2.58 L frontal elhrnoid attächûìent (posterior) cppl-ofaml IÎTNS 10.3 21 6 t.9 8.0 -1.10 R frontal ethmoid attachmenr (anrerior) m orr-cPa r mrns 60 l3 6 1.5 1.15 4.9 -0.85 R frontal ethrnoid attachr¡ìent (posterior) cp p r-ofa nr r mms 10. I 1.9 6 4.8 2 8.2 -l.00 l)imcnsions Posterior inferior width lnsl¡ns r nlfns 233 2.4 6 22.1 22.0 -0.54 Anterior inferior width nlil-nìir mms 240 2.1 6 22.9 29.6 2.61 A.nterior superior rvitlh morl-morr mms 16.9 1.1 6 16.9 25.1 5.18

Posterior superior u,idth olam | -ofam r ITms 11.3 24 6 16.8 -0.2r 18.5 0.50

AnL lareral projectiorr ol' laLera[ ¡tlaLe rilil-mo rllrnorr-nlir d"g 348 4.9 6 3r.2 -4.13 24.0 -2.20

Post lateral pro-jection of LaLeral plare rn s l-ofanr l/ofam r-rn s r d"g 25.0 12.4 6 41.2 1.3 I 41.8 1.84 Cribrifonl PLate

L anterior cribrilbnn platc I c-cpal nìr'tìs 63 13 6 6.5 0. l5 20.6 11.00

L lateral cribriform plaLe cpa l-cppl mrtìs t69 1.4 6 22.4- 3.93 14.5 -r.1 1 L posterior cribrilonn platc cs -cppl nìnìs 5.0 l3 6 5.9 0.69 ?o 2.23 R anterior cribrifonl plare lc-cpa r mms 5.9 l.l 6 6.9 0.91 20.5 13.27

R lateral cribriform plaLc cpâ r-cp P r mms l 8.3 1.9 6 22.1 2.32 t7.1 -c.ó3 R posterior cribrifonn plaLe es -cpPr mms

Iì angle lateral cribri[onn plaLe cf SN s -nlcpa r-cppr d"g 7.1 2.1 6 1.5 -2.30 23.5 5.85 Medial angle of platc cl SN lr-s/cs-lc d"g 19 3.1 6 2.1 - 1.41 -0.05 Medial Platc Distances Anterior heighL crista galJì lc-cg mms 6l 2.5 6 6.4 o.t2 23 -1.52 l)ostcrior height crista galli cg -cs mms 18.7 266 21.4 1.04 28.6 3.81 Sphcno-ctfuntritl rncrlial platc.jllìcti()rì cs-\/cs nìnìs 14 0 25 6 11.7 -o.92 16.6 t.04 Ethmoid-vonlcrirre juncLiorr vcs-vcl InÙìs 13.6 3.6 6 12.4 -0.33 1.1 -1.64 Septâl attachmcnt vct-11 n)nìs 285 t.t 6 29.O o.z9 41 .1 1.16

Nasal projectiorr r-fc nìin s 1.9 1.5 6 ot 0.87 4.4 -2.33 Dimensions Maximurn mcdial platc hcight vcr -cll nùns 252 4.5 6 z0;l 40.0 3.29

Maximum rncdial platc lcngLh n -cs ûìrns 103 1.5 6 35.9 5-t3 32.3 I JJ

Appendix2 Page xxxi Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Two Years of Age (continued):

2 Ycar Standard Paticnt JS Patient IP

Anatomical Unit Dcfìnition unit mcan sd n Valuc 7 Value Z

SPHENOID Lesser Wing Dis Lances L medial wing o[a¡nl-acl mrns 9.5 1.0 6 l 1.8 8.7 -0 80

L lateral wing (posterior) a cl-spal tnrns 24.8 r.5 6 23.8 -0.61 32.2 493 L lateral wing (antenor) spal-cs mms 298 3.6 6 29.4 -0.11 3'7.9 225 R medial wing ofam r-acr rnms 104 l9 6 12.9 1.32 8.8 -0 84 R lateral wing (posterior) acf-spilf rnrns 25.0 3.0 6 27.6 0.87 35-3 343 R lareral wing (anterior) spâr-es I¡;NS 30.6 4.0 6 334 070 43.4 320 Dimensions

Maximum lesser wrng rvidth s pal -spa r mms 58. I 64 6 6l .3 050 72.1 2.19 Lesser wing superior anglc spal-es -s¡rar d"g 144.7 48 6 t54.7 2.08 124.6 -4.19

L lareral projecrion (anterior angle) n -s/acl -spai d"g 536 4l 6 60.? t.73 59.8 1.51

R lateral projecrion (anrerior angle) n -s/ac r-s Pa r cl"g 56.6 45 6 65.5 l.98 61 .3 1.04 Prerygoid Plate Dis tances L medial pterygoid plaLe pLsl-hpl ntrns 18.9 r.1 6 20.8 13.8 -3.00 L medial hamular notch hpl-hnl INfNS 3.5 1.5 6 4.0 033 5t 0. 13 L lateral hamular notch hrü-pttl [ìnìs 8.4 't.l 6 6.2 5.9 -t.41 L lateral pLerygoid plate pLll-fool mrns 16.3 l3 6 16.3 r 3.1 -2.46 R rnedial pterygoid pìaLe pts r-h pr tnms 19.0 2.0 6 21 6 16.3 -1.35

R metlial hamular nolch hpr -h rr r rnms 21 6 3.9 -0 4.2 0.05 lì lateral harnular notch hnr-¡>tlr nìnìs 8.9 2.4 6 7.9 6.8 -0.87

[ì. lateral pterygoid plate ptl r- f oor nìfns 16.0 t0 6 t59 -0 I 15.0 -l00 Angles

L pterygoid axis n -s/ptsl -hpl d"g 55.0 13 6 64.2 94.1 5.36

R pterygoid axrs n -s/pts r- hpr deg 58.1 .5.8 6 68.9 93.5 6.00 Greater Wirrg Dis!ances Lateral

L anterior middlc cranial fossa fosl-gwll nìtns 29.8 1.4 6 32.1 1 33;7 2.19 L spheno-zygornatic suture zlsl-gwll tnms 13.2 12 6 12.9 -0 31 .3 20.08 R anterìor middle cranial fossa los r-g wl r nìrns 29.9 2.0 6 28.9 -0.50 3 1.3 0.70 R spheno zygomatic suture gwlr-zlsr mms 128 2.2 6 t49 0.95 313 841 Orbital L rnferior lateral orbital length gwll-grvml mms 23.6 1.1 6 23.9 o.z1 29.4 5.27 L superior orbital fissure heighr grvml-sob[1 ININS 11 6 4i 6 t5?, -0 .53 3'7.6 4.44 L spheno-frontal suture (orbital) sobfl -zf'sl rì1nìs l1 5 4.2 6 l8 7 029 l5.l -0.5'7 R inferior lateral orbital length grvlr-grvrn r nìnìs 23.1 1.9 6 t9-3 29.t 3.16 R superior orbital fissure heighL grvrrt r-sohf r mtns 15.-5 49 6 14.6 -0 l8 38. I 4.61 _) 11 l( spheno-frontal suture (orbital) s o bl r-zls r ININS t9.2 3.4 6 16.3 -0.85 1t.1 Posterior L sphcno-petrous temporal suture (irrf) fosl-pLsl rntìs l3 I l9 6 10.9 -l.l 15.3 1.16 R sphêno-perrous temporal suture (inf) fosr-[)ts r Ûnns l4.l l8 6 I 1.5 t4.l 0.00

L postcrior rniddle cranial fossa [osl -¡rcLa I nìtììs r69 I4 6 l8l 21.5 329 -0 Iì ¡rosterior middle cranial fossa [o s r-¡rcLa r nlilìs 31 8 25 6 300 33.9 0.84

Page xxxii Crouzon Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Two Years of Age (continued):

2 Ycar Standard Paticrit JS Patient IP

Anatomical Unit I)clinition unit mcan d n Valuc Z Valuc Z

SPHENOID (continucd) Drmensions and Ângles

Posterior sphenoid witlth I osl -fos r mms 433 3.9 6 31.6 39.1 -0.92 L angle of greater wing spla)/ zfs[-gwml-pLsl d"g 134.9 56 6 112.1 t28.5 -t.14 R angle of greatcr rvirg splay zfs r-gwm r-pLs r deg 132 I 6.1 6 I12.8 2.99 132.6 -0.03

Total angle of protrusion zf sl -g w nr I /g rvrn r-zlsr deg 95.8 4.t 6 I19,0 89.1 -1 49 Inferior greater wing protrusion grvlJ -gwrnl/gwrrrr-gwÌr deg 94.4 5.9 6 tt6.4 3.'73 148.4 9.15

Posterior angìc of grcater wirìg f os I -pcta[/pera r-fos r dcg 95.2 87 6 80.0 1.15 69.f -2.98 Squamous SphenoirJ

L squamous spheno-fronLal suture z-l s [-s pc I mms 18.5 3.0 6 L squamous spheno-parietal suture spc[-sptl mms 109 1.9 6 L lateral spheno-temporaI suLurc fosl-spLl ltìrns 40.1 1.9 6 R squamous spheno-frontal suture zfs r-spc r mrns 11.3 3.2 6 R squamous spheno-pârietal sulure spcr-sptr mtns 106 2.8 6 R [ateral spheno-ternporal suture fos r-sptr Ûìnìs 31 1 2.0 6 Sphenoid Body Distances Lateral/Posterior Il od¡, L anterior inferior length grvrnl-ptsl mms I 1.8 1.2 6 13.9 L75 15.0 2.67 I- spheno-occipital synchondrosis (laL) ptsl -petal nìrns t2 l 0.9 6 13.4 1.44 21.4 10.33 L posterior cliroid heighL petal-¡>cì mrÌs 1.1 2.3 6 1.4 0.13 8.9 0.78 Posterior cLinoid width pcl -pcr nìtns 84 1.8 6 8.9 0.28 tr.2 l.56

lì anterior inferior lengrh gwmr-ptsr nìtns 12 1 t.2 6 13.4 14.4 t.92

[ì spheno-occi¡>ital s),llchondrosis (lat) Pts r-pcla r [ì¡lìs 13 0 0.9 6 13. I 0.11 19.0 6.61 '7.9 R posrerior clinoid heighr Pcta r-Pc r mms 21 6 8.9 8.1 0.r0 Anterior Body l- spheno-ethrnoid srrtu rc cs -cppl nìms .50 1.3 6 5.9 069 '79 2.23 L anlerior lateral distancc cppl-o[arn I nìnts l0 3 2.1 6 1.9 8.0 -1.10 L anterior superior letrgth ofarnl-grvrn I nì¡ns 8.4 0.9 6 8.1 -0.33 r0.7 2.56 R spheno-ethmoid suture es-cpPr ININS 5.2 1.3 6 5.5 0.23 10.8 4.3t R anterior lateral distancc cppr-ofarn r mms 10. I 19 6 4.8 -2.79 8.2 -1.00 R arìterior superior length ofam r-grvm r nìms 92 01 6 9.0 -0.29 9.9 1.00 SelIa

[- lateral anterior bod¡, cppl -ofprnì mnìs tz.6 1.1 6 8.1 -2.65 8.4 -2.4'7

L lateral sella lengLh ofprn [-petal Ûult s t] 6 1.4 6 11 .6 0.00 25.2 5.43 R lateral anterior bod), cppr-ofprn r lnnìs 12.5 1.9 6 1.2 -2.79 9.5 -1.58 l{ laLeral sella length o[prn r-petar mrns 18.0 1.5 6 185 033 23.5 3.6'l Base/Floor 13ody jrrrrctiorr Spheno-eLhmoid rncdial platc cs-vcs nìnìs r 4.0 25 6 |1 -o.92 r6.6 1.04 Spheno-vomerirre junctiorr VCS h nìnìs r0 9 30 6 ll4 0.17 r 6.6 1.90

L posterior width h-pLsl nìnls ll6 Iu 6 l1.9 0.17 1 1.6 0.00 R posterior *'idth h -pts r nùtìs |5 1Z 6 n.4 -0.08 10.0 1.25

Appenüx ¿ fage xxxut Appendix 2 Measurements for the Bxperimental Standards and the Patients with

Crouzon Syndrome:

Two Years of Age (continued):

2 Ycar Standard Paticnt JS Patiônt lP

Anatomical Unit Dclinition unit mcan sd n Valuc Z Valuc Z

SPHENOID (continued) I)irnensions Anterior inferior body w.idth grvrnl-gwmr mms 2t.3 1.9 6 166 r6.2 -2.68

Spheno occipiral synchondrosis (inf ) pt s I -ptsr rnms 19.9 2.4 6 2Q2 013 18.0 -0.79

Anterior super.ior body width <>[a nl l -ofarn r IIIMS 11.3 2.4 6 16.8 -0.2t 18.5 0.50 Spheno-crccipital synchondrosis (sup) pctal -petar rnms l8.u t] 6 15.5 -l t] .6 -0.71 I. posterior body height pcl-pLsl trms I5.0 236 184 I 24.9 4.30

R posterior body heighL Pcr-pl"s r rn nìs r6.3 2t 6 l8 6 l.l 22.6 3.00 L anterìor body height acl grvrnl IÌìnlS 9.6 l.l 6 88 -o.73 I t.7 l.9l L anterior body height acr-8wnì f rntns 9.8 0.8 6 10.0 12.2 3.00 Angles Body floor angle cs-vcs-h .l"g l3l .8 21 8 6 It.1 0 119.2 -o.45

L lower body angie s -n/grvrn l-pts I d"g 46.0 3.1 6 34.8 3.03 33.5 -3.3 8 Iì lower body angle s-rt/grvrnr-1:tsr d"g l -58.8 2.O 6 160.0 162.1 r.95

L upper body angle s -n/o f prn I -pctal deg 233 2.8 6 11 0 9.8 -4.82

[ì upper bo<1y angle s -n/o fprl r-peta r dcg 21.5 3.3 6 201 10.8 -3.24

,IEMPOIìAL l)is tances Squamous

L latcral spheno-temporal suturc fìrs I -s pLl nìrns 40. I t9 6 L tem¡roro-parietal suture sptl-asl ININS 62.4 31 6 L occipital mastoid heighL as l-¡nal mÍìs 33.2 3l 6

L medial mastoid prorninence rn al -srn f I rnrns 8.2 22 6 17 R lateral spheno-temporal suturc fosr-sptr tnms 20 6 [ì temporo-parietal sutu re sl)tr asr nilns 61.'7 66 6

R occipital mastoid heighL ¿¡ s r-In ar nìrns 31.0 43 6 lì nrctlial mastoid pronrirrencc r¡rar-srnlr nìrns 9.9 22 6 105 ExLemal Auditory Meatus (EAM) L lateral rnastoid promirence rnal-carnil nì[ìs 14.2 15 6 t46 13.9 -o.20

L infcrior-posterior EÂM rirn ca ln i I-oanr ¡; I mrns t.t 1.9 6 t5 0ll 111 2W L posterior-superior EAM rim oarn pl-pol [ìÍlls 49 03 6 45 - t.J5 7.8 9.6'l L superior-anLerior EAM rim po[-canral tntns 49 0.9 6 4.4 10.3 6.00 L anterior-inferior EAM rirn carnal calril rnlns 5.5 t4 6 54 6.0 0.36 R lateral mastoid prominence nìar-can]lr nìÌlìs 14 0 l9 6 16 t I t1 13.2 -0.42 R inferior-postcrjor EAM rim carnl r-eänìPr nìrìts 6.3 2.3 6 8.5 16.8 4.51

R posterior-superior EÂM rirn eanlpr-Por mms 4.8 06 6 41 -0. 1 5.6 1.33 R superior-anterior EAM rim l)or-cama r nì[ls 4.6 l6 6 3.0 6.3 1.06 l{ antcrior-infcrior ll¡\M rim c¿ìrn¿tr-eaûì tr lnlì1s 54 06 6 6.2 1.3 13.1 l 3.83

Page xxxiv Crouzon Synd.roma Appendix 2 Measurements for the Experimental standards and the patients with Crouzon Syndrome:

Two Years of Age (continued)

2 Ycar Stan

Anatomical Unit Dcfinition unit mcan sl n Valuc Z Valuc Z

TEMPORAL (conLinued) Zygoma

L EAM-anicular fossa lcngth eamal_afl ITìJIì S 104 r.5 6 10.2 -0. l3 14.0 2.40 L articular fossa heighr afl_ael mms 52 ll 6 8.0 2.55 4.1 -1.00 L inferior arch lengrh ael_parl mms 1.7 34 6 6.8 -o.26 12.2 t.32 L zygomatico-rentporal suturc parl_ztl mms 163 2.t 6 14.8 -o.t I 17.7 0.61 L superior arch lerrgth zLl_¿ul rnms 26.6 2.1 6 11 a 16.3 -4.90 R EAM-articular fossa lengrh eamar_afr nìms r 1.3 t4 6 9.8 -r.o1 8.1 -l.86 R anicular fossa height alr_acr nùlì s 48 1.2 6 7.1 2.42 3.2 -1.33 R i¡ferior arch lcngLh aer_parr mnìs u1 3.8 6 1.6 -o.29 -0.26 R zygomatico-Lcmporal srrturc parr_ztr nìms 170 206 r3.5 -r.7 5 20.1 1.85 R superior arch lengLh zû_aul nuns zl 8 23 6 23.4 -l.9r 13.3 -6.30 Petrou s

L spheno-perrous temporal sutLrre (sup) fisl_peral rnms 15.8 l.ó 6 15.2 -0.3 8 18.8 1.87 LposL-med ternporo-occipiral sururc pcral_jfpl IÍJN S 25.6 1.8 6 28.O t33 27.5 1.06 LlateralLernporo-occipitalsr¡rure jfpl_asil min s 368 4.8 6 L petrous superior rnargin asil_pcral Ítms 544 3t 6 Iì spherro-perrous ternporâj sLrrurc (su¡r) lisr-peLar rruns 15.8 t.2 6 15. l -0.58 14.1 -0.92 I{posL-medrcrnporo-occipitalsuturc petar_jfpr mnìs 21:6 2.3 6 25.2 -1.04 26.8 -0.35 Rlateralremporo-occipiLalsurure jl,pr_asìr fftms 37.3 4.4 6 R petrous superior rnargin asir_perar mms 53.3 4.0 6 L occìpital masLojd surt¡re inlcrior mat_jfll tnms 143 2.9 6 16.4 0 24.1 3.38 L jugular foramerr rvidLh jfÏ-jfml mms 8.5 1.8 6 75 5.7 -1.56 L medial renrporo-occiJtiLal sr¡rLrre (inf) jtrnl_pLsl mrns 21 .3 t.t 6 21.8 n?o 30.0 5.12 L spherro-¡xtrous temporal suture (irrl) iosl_ptsl mrns l3.l l9 6 10.9 -1.1ó 15.3 1.16 [ì occipiral masroid surr¡rc inf erior rnar_jflr rnnìs 136 18 6 18.0 2.44 22.8 5.11 R jugular forarnen rvidrh jflrjtnrr mms 99 0.8 6 5.6 5 7.3 ,3.25 Iì medial renì[Ðro-occipiral sururc (irrl) jfrnrpLsr fntn s 220 236 25.O I 21.8 2.52 R spheno-perroLrs rcmporal sLrLure (irrf) fosr_¡rtsr rnrns 14. I 1.8 6 I1.5 I 44 14.1 0.00 Dimensions

L perrous ndge lengLh peral_perpl mms 46.7 4.1 6 52.6 1.44 64.6 431 R petrous ridge lengrh pcrar_perpr mms 41J I 24 6 62.8 5.83 61.9 7.96 Inrer-intemalaud lneattrsclinrension iarrlr_iarnl ntnìs 3.t 3 2.6 6 30.1 3 8.6 Inter-extemalaudrneaLusdirnension 1.27 ¡tol_por nìms 739 4.4 6 l1.o -0.ó6 101.7 6.32 Inter-post jugular foranrcrr rlimerrsion jlprjfpl rnms 424 3.tì 6 45.0 0.68 39.3 -0.82 lnter-mastoid dirnonsioll nralrnar mms 7l .8 30 6 7l .0 -o.27 '16.1 1.43 Angles

AudìLory canal angle pol_iaml/iarnr_1rer d"g 140.1 626 r 49,8 147.1 1.03 Petrous ridge anglc perpl_pcral/perâr_pcrpr deg 95t 35 6 8l .0 -4.O3 90.8 -t.23 L zygoma projecrìon anglc ¡reraì_aul-zrl d"g 974 5.1 6 r 11.8 2.53 89.0 -1.41 R zygoma projecLion anglc pelâr-âur_ztr d"g 937 6 14 98.6 0.6ó 929 -0.1 1

Appendix 2 Page xxxv Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Two Years of Age (continued):

2 Year Standard l)aticnt.JS I'atiônt IP

Anatomical Unit Dcfinition unit mcan sd n Valuc Z Valuc Z

PAzuETAL Distances Sagittal suture l-br rnms 99.2 43 4 L parietal frontal (coronal) suturc br-spcI mms 80.6 36 4 L spheno-parietal suture spcl-sptl mms 10.9 l9 6 L remporo-parietal suture sptl-asl rnnìs 62.4 l7 6 L occipito-parietal (lambdoid) suLu rc asl I ilìrns 12.9 20 6 R parietal lrontal (coronal) suLurc br-spcr nìtns 80.7 54 4

R sphcno-parietal sutt¡rc spcr-sptr nìfn s 106 2f\ 6 l{ remporo-parietal suture sptr-a sr Ûr¡s 6t1 66 6 R occipito-parietal (lambdoid) suture asr-l rnrns 14.8 32 6

OCCIPITAL Distances Lambdoid and Cranial Base

L occipito-parietal (lambdoid) sutLrre | -asl lntns 12.9 2.O 6

L lateral temporo-occipital suture (sup) asl -jfl I tntns 34.7 5.1 6 L lateral jugular foramen jtll-itpl Intns 5.0 1.3 6 64 1.08 2.6 - 1.85

L rnedial jugular forarnen jtpt-jturl ININS 1.1 1.9 6 (r5 -o.32 65 -o.32 L medial temporo-occipital suturc (inf) jtrnl-ptsl nìIlìs 21.3 1.1 6 21 I o.29 30.0 5.12 ll occipiLo-parietal (larnbdoid) suLure l-asr rnrns 148 3.2 6 R lareral temporo-occipital suture (sup) asr-jflr rÌìms 32.4 4.4 6 Iì lateral jugular foramen .iflr-jfpr [ìms 5.8 1.6 6 5.5 -0. l9 3.4 - 1.50 It medial jugular foramen jfpr-jfrn r rn nìs 1.4 t.] 6 2.8 -21t 6.1 -0.76 R medial ternporo-occipiLal suturc (inf) j frn r-ptsr Itìms 22.0 2.3 6 25.0 130 21.8 2.52 Inferior spheno-occipital synchondrosis pts r-ptsl mtns 19.9 2.4 6 202 013 18.0 -0.19 Foramen Magnum

L anterior foramen magnum ba-frn U nìrns t].4 1.0 6 l8 6 1.20 19.5 2.t0 L posterior foramen magnum tinl[-o rnms 21.9 t.4 6 t] z -3.36 t9.6 -1.64

lì anterior forarnen rnagnunì ba -f¡n I r rnnìs t] .l 0.4 6 r 9.0 4.15 16.6 -1.25 Iì posrerior foramen magnurÌ frnlr-o Ûì fns 22.3 15 6 200 -l .53 27.9 3.73 l)imcnsions Foramen Magnurn Forarnen magnum length ba -o Ûìnìs 30.5 l6 6 280 310 031 Forarnen magnum width lìnll-fmlr rìlftìs 23.8 t4 6 24t 0.2t 26.O 1.51 Posterior Cranial Fossa () Posteriol crarúal fossa depth u-ro[) I iltIts 34.5 39 31 1 39.3 t.23 Posterior occipital height iop-l nìnìs 51.3 30 6 L posterior fossa length pctpl-iop ûìrns 56.fÌ 24 6 51 .3 _) )a 58.2 0.58

L posterior fossa length PctPr-roP nìms 58.2 )'1 6 46.4 -4.31 58.2 0.00

Page xxxvi Crouzon Syndrome Appendix 2 Measurements for the Bxperimental standards and the Patients with Crouzon Syndrome:

Two Years of Age (continued):

2 Ycar Standard Paticnt .IS Paticnt IP

Anatomical Unit Dcfïnition unit mcan g| n Valuc Z Valuc Z

CRAMAL BASt] SLI'I'URI]S Anterior Cranial Fossa spheno-er}rnoid L synchond rosis cs-cppl nìrns .5.0 l3 6 5.9 0.69 7.9 2.23 R spheno-ethmoìd synchondrosis es-cPPr m¡ns 5.2 13 6 5.5 o.23 10.8 4.31 L spheno-fronral sururc (ant fossa) cppl-spal mrns 25.5 3.9 6 24.5 -o.26 31.0 1.41 R spheno-frontal suture (anr [ossa) cPP r-s pa r rnms 26t 4.4 6 28.3 0.50 33.7 t.73 L spheno-frontal sururc (orbiral) spal-zlsl rnms 155 16 6 128 -1.69 11.9 I{ spheno-frontal sLrrure (orbiral) spar-zl'sr mms 14.9 266 10.4 -1 t3 9.9 -1.92 L sphcno-zygonìalic su[urc z-[sl-gw ll ûìrns 13.2 t2 6 12.9 -n t5 3'7.3 20.08 R spheno-zygornatic sut rt re z-fs r-g rv I r mÍìs l2.rJ 226 149 0.95 31 3 8.41 Mìddle Cranial Iìossa spheno-squarnous l- terÌì[)oral suturc grvlì-lisI nln s 28.4 0.9 6 3l .l 3.00 3t.2 3.1 l R spheno-squanìou s tcill[nral suLu re grvlr-li sr mms 2fa 4 226 28.5 0.05 30.2 0.82

L spheno-petrous remporal (sup) i sutr¡re f sl -pcLa I lÌms l5.ti l.ó 6 15.2 -0.38 18.8 t.8'7 R spheno-petrous Lem¡toral sUturo (sul)) fi s r-pcta r mtns l5.u 12 6 l5.l -0.58 14.1 -0.92 L spheno-pcLrorrs tcmporal sLrruru (irrl) f os [-pts I nlÛìs l3 I 1.9 6 r0.9 - 1.16 15.3 1. l6 R spheno-petroLrs rcrn¡roral suturc (irìl) lbs r-pLs r nìtns 14 1 l8 6 1r.5 -l 44 14. r 0.00 Posterior Cranial Fossa

L rnedial temporo-occil)iral sLrLure (sup) petal -jf nrl nìms r9 l 19 6 21 1 t.37 21.8 1.42 Iì medial ternporo-occi¡rital (sup) surure ¡rcLa r-j I rn r mrns 192 28 6 22.8 1.29 21.1 0.68 L medial temporo-occi¡riral srrture (inf) jlìn l-ptsl tnms 21.3 1.1 6 21.8 o.29 30.0 5.12 R medial temporo-occipiLal sururc (irri) jl'rnr-pLsr rnrlìs 220 236 25.0 1.30 27.8 2.52 L occipital masroid suLure (supcrior) jfll -pctpl ûìms 30.4 5.1 6 35-3 0.96 46.'7 3.20 R occipital masroid surure (superìor) jfl r-pcq; r nlÙts ,o'ì 4.2 6 45.5 3.86 51.9 5.38 Spheno-occipital synchondrosis (sup) pclal -Pcta r Ììms 18.8 t] 6 15.5 t.94 t7.6 -o.ll Spheno-occipital s¡,nchondrosis (irf) pLsl-ptsr mms 19.9 2.4 6 20.2 0.13 18.0 -o.79 I- spheno-occi¡riral synchondrosis (lar) pLsl-pet al mtlìs t2.t 0.9 6 13.4 1.44 21.4 10.33 R spheno-occipiLaì sl,nchondrosis (lar) ptsr-peta r nùns 130 0.9 6 13. I 0.11 19.0 6.67

CRAMAL BAST] Facial Heights

Anterior facial heighr rì-8n mms 689 11 5 868 2.52 102.8 4.11 L ¡rcsterior facial hcight s -gol Ùiltìs 500 34 5 526 o.16 5s.9 114 Iì posterior lacial hcighr s-Bor Tlì rì s .5t 3 42 5 51 3 0.00 56.9 1.33 Facial Angles

SNA s-n-ss d"g 18.9 26 6 18.6 0.12 52.6 -10.12 SNB 't2 s-tì-sÌt d"g 6 24 5 683 lt9 51. t -8.96 Cranial lìasc Ârrglc Cranial base angle ba -s -rr d"g 135 I 5.i 6 128.6 - 1.18 t62.1 5.O2 Cranial ßase Dirncrrsions Cranial basc lcngrh b¿n mms 12.1 226 71 8 -0.l4 86.3 6.45 Clivus (¡rostorior length cran ial basc) bar nìrns 266 2t 6 21 3 o33 302 1.11 Anterior cranial basc lcrrgth s-n IlUÌìS 5t 4 2.i 6 51 .5 0.04 51.0 2.43

Appendix2 Page xxxvti Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Six Years of Age:

6 Ycar Standard Itaticnt LW Paticnt AY

Anatomical Unit Dcfinition un¡t rncan sJ n Valuc Z Value Z

MANDIBLE Dis tances

L anterior superior body id-em lil mms 36.0 4.0 6 31.8 r'7.9 -4.53 L posterior superior body crn lil-cbl rtrns 129 4.5 6 22.5 213 32.1 4.40

L total superìor body i d -cbl mms 45.3 3.9 6 51.5 48.7 0.87 L anterior rarnus cbl -cLl mms 26.3 l3 6 21 .9 t-23 23.6 -2.08 L anterior mandibular norch ctlrnnI rnrns 13.8 0.1 6 14.6 I .14 13.3 -0.71 L posLerior mandibular notch rnnl-cdl mÍìs 14 8 l4 6 I 8.1 l6.l 0.93 L posterior ramus cdl -gol nìllìs 35.8 30 6 40.8 l.6l 30.6 -t.13 L inferior body gol-gn mms 60.1 50 6 65.3 62.8 0.42 R anterior superior body id-orn I ir rnms 358 4.2 6 281 -t 69 n.4 -4.38 I{ posterior superior body cm I i r-cbr rnms 10.2 4.5 6 25.5 340 30.1 4.56 R toral superior body id-cbr m[)s 45.0 3.5 6 51 3 1.80 46.2 o.34 Iì anterior ramus cb r-ct r nttns 21 8 t4 6 274 -0.29 286 0.57 Iì anterior mandibular notch ctr-tÌì n r rnms 13..5 l0 6 13.6 0.1 0 l 4.l 0.60 lì postcrior r¡rantlibular notch rn rr r-cd r nìnìs t56 11 (¡ I tì.4 165 16.3 0.41

lì posterior ramus ctlr-gor rTì il'ts 363 24 6 393 341 -0.67 I{ inlerior body gor-8n ININS 59 1 55 6 66.6 61.2 o.27 Dimensions

Intcrgonial dìmension gol -gor tntns 10.3 6.5 6 11.0 0.1 I 66.6 -0.51 Intercondylar dimension cdl-cd r rnms 91. l 6.1 6 9l.9 0. l3 92.8 o.28 lntercoronoid base dimension cbl-cbr mrns 62.3 51 6 64.1 61.7 -0.t I lntermola¡ dimension ernlil-ernlir nìms 5tz 3.6 6 48.5 -0.7 31.2 -5.56 L Superior ramus width cdl-ctl nìms 23.5 1.6 6 25.1 26.5 1.88 L inferior rarnus width gol-cbl mtns 25.0 24 6 29.4 1.83 30. I 2.12

R superior ramus width c(l r-ctr nùns 23.3 1.5 6 24.0 0.41 25.O 1. t3 Iì inferior ramus width gor-c[>r nìrns 25.t] 2t 6 21.1 29.0 1.52 Antcrior symphyseal heighr gn-id mrns 22.0 1.6 6 25.2 21 .4 3.31 L total mandibular length gn-cdl mlns 87. l 5.6 6 94.6 t.34 87.8 0.13 lì toLal mandibular length gn-c

L mandibular notch angle cdl-mnl-ctl deg nt.1 91 6 99.5 -r.26 128.2 1.70 Iì rnandibular notch anglc cdr-rìrìr-ctr dcg t13.4 1.fl 6 95.8 -2.26 l l0.l -o.42 L gonial angle cdl -go[-gn .i"g 121.9 4.3 6 124.3 -0 84 131 4 2.21 R gonial angle cd r-g o r-g n d"g 126.2 4.3 6 126.3 0 136 0 2.28 L coronoid base angle ctl -ct;l -i d deg 126.0 11 6 t26.5 0 r39.3 t.13 Iì coronoid base angle cLr-cbr-id dcg 126.2 59 6 tzj 9 1 34.1 1.34 L coronoid-dcnLal base angÌc cLl-cbl-cnr IiI dcg 140.9 16 6 t35 2 -0.1 l3 8.8 -0.28 Iì coronoid-dental base anglc ctr-cl;r-enr I ir d"g 141 5 10.0 6 t37.5 137.4 -0 4l

L symphyseaì angle gol-gn-id d"g tì4.3 4.0 6 90.1 I 81 .4 0.11 Iì symphyseal angle gor-gn-id d"g 872 1.9 6 rJ3.5 -l 95 85.6 -0.84 Anterior nrandibular angle go[-grr-gor deg 70. I tt 6 6.5.1 -t 649 - 1.58

Page xxxviii Crouzon Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Years of Age (c

6 Ycar Standard Paticnt LW Paticnt AY

Anatomical Unit Dcl'inition unit mcân d n Value Z Valuc Z

MAXILLA Distances Orbital Region L fronto-maxillary suture snm[-morl rnnìs 6.1 i.l 6 15;l 8.18 10.6 3.55 L frontal proccss orbital rirn nlil-morl ITIMS 14.3 l6 6 8.3 3.15 9.7 -2.88 L medial orbital floor r.¡rsl-nlil mrns 280 1.5 6 31 .0 21.1 -0.60 L posrerior lateral orbital lloor msl-iobll rnms 179 2.3 6 20.1 0 24.6 2.91 L anterior lateral orbital lloor orl-iobil mms 16.5 25 6 17.0 15.6 -0.36 L maxillary infra-rrrbitrl ril¡ orl-nLil nìtns t29 2.4 6 21 5 3.58 20.5 3.11 R fronto-maxillar), suttì re sntnf-rnor mms 1.3 15 6 13 3 4.00 1.8 0.33 Iì frolrLal proccss orbital rirn nììr-lnorr mfns 14 I l8 6 9.3 -2.61 9.5 -2.56 21 R medial orbital f loor ¡nsr-nlir mrns 21 .5 24 6 31.0 1.46 9 0.i7 I{ posrerior lateral orbital floor msr-iobfr ÛlÛìs lu 3 3l 6 227 r.42 2s.5 232 R anterior latcral orbiLal floor orr-iol¡f r mÍts t6.2 2.1 6 t] .9 0.ó3 13.9 -0.85 I{ maxillary inf ra-orbitaì rirn orr-nlirr ûìnls t24 zÍ\ 6 21.O 3 2t.o 3.i0 Anterior Wall L anterior zygo-rnaxillary suturc znril-orì rn Ûìs zt9 15 6 t] .3 3.O1 22.3 o.21 L lateral maxillarl, v¿ll zrnil-crnlsl m[ìs 14.8 1.4 6 20.6 4. 28.0 9.43 L anterior ah,eolar rnargin cnrlsl-pr mrns 364 3.3 6 32.3 21.6 -4.48 -0.61 L lower pyrifonl rnargin ans -al I rnms 126 1.5 6 16.3 1 1.6

L upper pyri{onn rnargin all-i¡m I mms 13.8 1.4 6 11 .1 2.'t9 t'7.1 2.79 L naso-maxillar¡, suturc inml-snm I nìms t] 6 1.8 6 16.2 -0.78 15.6 -1.11 I{ anterior zygornaxillary suturc ztnlr-orr mms 20.9 l9 6 t'l .7 -1.68 235 1.3'l R lateral maxillary wall zmir-em 1s r mms 14.9 1.2 6 21.4 5.42 28.2 1 1.08 R anterior alveolar marglrr crnlsr-pr flìllì s 350 31 6 31.4 -0.97 21.5 -3.65 R lower pyrifonn nrargin ans-alr rnms 13 0 t7 6 l5.l t-24 1t.4 -o.94 r -0.14 lì Lrppcr pyrilonn rnargin a I r-inm r mms 14.2 2.2 6 25.2 3.9 L naso-maxillary suturc uìrn r-snm r mms 18.0 236 9.8 3.57 15.4 -1. 13 Anterior alveolar height pr-a ns mms 13.5 9.3 6 14.5 0.1 I 14.0 0.05 Lateral WaIl L posterior alvcolar nrargilr crnlslrnxtl mrns ll.l 2.4 6 t9.f 3-42 25.6 6.04 L postenor maxillary wall rnxL[{nsl mms 21 9 r5 6 28.2 0.20 30.1 r.41 L postcrior Iateral orbital lloor rns I iol¡l'l mms 11 9 236 20.1 0.96 24.6 291 L posterior zygo-rnaxillary suture iobll-zrnil mms t'l 6 lt 6 l8 4 o.'13 18.4 o.13 R posterior alvcolrr rrtargirt cnì I sr-nìxtr mÍìs t2 0 12 6 19.3 6.08 23.3 9.42 Iì posterior maxillaq, s,all fììxtrJns r fnfns 28 I 12 6 323 3.50 329 4.00 11 1 R posterior larcral orbiLal lloor rnsr-iobl r INMS I tì.3 3l 6 25.5 2.32 [ì postorior 7-yBO nìaxillary strttrro iobf r- zl¡ ir ûlflìs t] 5 18 6 16.9 -0 33 191 t.22

[)a late 6.33 L postcrior palat:rl hcight cnr I sl -gpf I Inms 161 t2 6 21.9 433 243 -0.08 L posLerior palaLal rvidth gpfl-pn s IIÌNS 133 1.2 6 12.6 -0.58 13.2 6 22.9 3.93 25.3 5i3 R ¡nosterior palatal hcight enr'l s r-gpf r NìIÌS 17 0 15 R posterior palatal rvidth gplr-prr s Ínrts lz.9 0.8 6 13.5 0.75 15. l 2.75 Supcrior palatal lcrrgth âns-Prìs mrns 369 1.6 6 44.1 4.50 398 1.81

Appendix 2 Page xxxix Appendix 2 Measurements for the Experimental Standards and the patients with Crouzon Syndrome:

Six Years of Age (continued):

6 Ycar Standard Paticnt LW Patient AY

Anatomical Unit Dcfinition unit mcan sl n Valuc Z Valuc Z

MAXILLA (continued) Dimensions Anterior heighr midline rì -pr mms 5ll r.6 6 54.3 2.O0 49.2 -t.t9 L lateral heighL morl-er¡ I sl nìms 48.3 3.3 6 483 0.00 45.0 -r.00 R lateral height rnorr-ent I s r mms 41.5 4.2 6 48.8 0 3l 44.6 -0.69 L posterior heighr gpll-rn sl rnms 25.1 l5 ó 23 1 -l 28.2 1.61 R posterior heighr gp fr-rns r rnms 25.1 1.2 6 24.4 -1 30.1 3.61 L superior lengtlr rnsl-inr¡l mms 38 6 t9 6 456 3 41 Z 4.53 R superior lengti nì s r-tlì rì1 r fnrns 37.8 2.1 6 46.3 3 44.8 2.59 Posterior palatal widrh gpfl-gptr rntns 75.2 14 6 246 -0 43 26.4 0.86 Anterior in rer-canine widLh ccs I -ccs r tnms 31 8 236 33.8 0.87 29.6 -0.96 Maxirnum maxillary width znlil-z-nlir rnms 75.8 4.1 6 I5.3 -o l2 82.6 1.6ó Superior (inter-orbirat rim) widLh orl-orr nìfns 52.5 6.1 6 64.O l.?2 61.9 1.40 Nasal aperture heighr tì¿l-Arìs nìms 23.0 2.6 6 23.6 o.23 19.5 -1.35 Nasal apenure width all-alr IIINS 20. rl 2.1 6 23.3 0 11.6 -1.19 Angles l- orbital flcxrr angle nlil-nrsl-iotrll dcg 562 2.4 6 68.4 5 6t.2 2.08 Iì. orbital floor angle nlirrnsr-ioblr drg 54.3 7.4 6 65.2 I 56.1 0.24 L inferior angle ¡rosterior rnsl-gpfl-ein 1 sI d"g tÙz1 4.2 6 tzg.t tzt.1 4.38 R posterior inferior angle rnsr-gpfr-ern lsr d"g I 04. tì 7.5 6 136.5 423 116.7 1.59 Superior maxillary splay iobfl -rns l/rnsr-iob[r d"g 91.0 8.2 6 125.4 r02.6 0.68 L superior /occlusal angle snml-msl/em l sl-pr ,leg 40.1 2t.6 6 3 8.4 -0 ll 50.4 0.45 R superior angle /occlusal srtm r-msr/em l sr-pr deg 40.9 '¿0.3 6 4t.5 0.03 5t.7 0.53 L palatal/occlusal angle ans-pns/ernlsl-pr d"g 47.1 26.5 6 4'7.t 0 59.1 0.45 R palataVocclusal angle an s -pn s/em I s r-p r d"g 47.4 25.4 6 50.8 0 63.2 0.62 Anterior palatal angle gpll-ans-gpfr d"g 40.l 2.2 6 34.2 2 40-5 -0.09 Maxillary arch angle gpfl-pr-g¡;lr d"g 40.6 46.1 6 36.6 44.2 0.08

NASAL BONES Distances Nasal length tìa-n n)rns 16 5 2.2 6 20.9 18.4 0.86

L inferior nasal width a n -inrn I Intns 11 2.0 6 9.4 085 4.2 -t.7 5 L lraso-maxillary suture 't.8 inm l-snrnl rnrns t76 6 t62 -0.7 8 15.6 -l I I L fronto-nasal sulure n -snrn I niltìs 5.<) 1.5 6 3.5 1.6 l. l3 R inferior nasal widrh lìâ -ltì ¡n r []rì ts 8.2 2.5 6 l0 9 8.6 0. l6 I{ nasornaxillary suture ltìnì r-srì nì r Ìtìtììs I ti.0 2.3 6 9.8 -35 15.4 - l.l3 R fronto-nasal suture n -stìnì r nìnìs 59 0.1 6 i1 -3 I 96 5.29 Dinrensiu¡rs lnfenor widLh irrrnl-inr¡r nìnìs llti l0 6 120 il.8 0.00 Superior width snnll -snm r rnrns 96 l5 6 64 -2.t3 ll3 l. l3 Angles Nasal/anterior cranial base anglc s-rì-nâ d"g 96 ri 4t 6 109 6 3.12 942 -0.63

Superior nasal bone angle I snm -n -snln r dcg l0t.l 14.9 6 123 2 1.48 80.5 - 1.38 Inferior nasal bone angle -n inr¡l l a-ìnr¡ r d"g 103.0 20-8 6 1t.1 131.6 t.3 8 Splay of nasal bones inrnl-snml/snrn r-i nrn r d"g 8.6 3.5 6 zr.6 3.1| 9.3 020

Page xl Crouzon Syndrr.tmc Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Six Years of Age (continued):

6 Ycar Standard Pâticnt LW Patient AY

Anatomical Unit Dcfinition unit mcân $ n Valuc Z Valuc Z

FRONTAL Distances Supra-orbital '7.6 L fronto-nasal suture n-snr¡l mms -59 1.5 6 3.5 1.13 L fronto-maxiltaq/ suLure snml-morl mms 6.1 l.l 6 15.7 8 10.6 3.55 L superior medial orbital rirn rnorl-sori mms 16.3 l3 6 r 9.5 16.3 0.00 L superior lateral orbital rim sorl-slorl mms 26.5 2.2 6 2'7.8 0.59 30.6 1.86 Lfronto-zygomatic suturc (anterior) slorl-zll mms 13 09 6 10.7 3.78 10.8 3.89 LfronLo-zygomaticsr¡turo(laLeral) zll-zlsI mms 19 1.9 6 7;l -0.11 1.3 -o.32 Llronto-zygomaticsutnrc(rncdial) zlsl-slorl mms I 1.3 1.5 6 13.9 1.73 13.0 1. r3 Iì fronto-nasal suture n-srì¡nr mrns 59 0l 6 3.7 -3. l4 9.6 5.29 R fronto-maxjllar), sutt¡rc snrrr-nìorr ûìnìs 73 1.5 6 r3.3 4.tn 7.8 0.33 R superior medi¿l orbital rln morr-sorr rnms 1'1 9 l0 6 24.1 6. 17.3 -0.60 Iì superior latcral ortrjLal rirn sorr-slorr mms 21 3 1.8 6 1)) -2.83 29.3 l.ll Iì fronto-zygonrâtic sutrrrc (antcrior) sl<¡rr-z-fr NìIlìS 6tÌ 0.8 6 8.9 1 1.0 5.2s [ìfronto-zygornaticsr]turo(laLcral) zlr-zlsr Ûlûìs S3 13 6 9.0 8.7 0.31 Rlrorìto-zygoûlaticsrrtt:rc(nrcdial) z[sr-slorr IììII'IS ll3 14 6 13.9 130 1.21 ELhmoid aa1 Nasal root projection n-lc mms ll6 15 6 8.2 t3.2 1.07 L fronto-ethmoid attachrnent (anterior) [c-cpal nlms 7.2 t.4 6 6.5 -0.50 1.3 0.07 L fronto-ethmoid âttâchment cpal-cppl nìnls 2t.o 3.0 6 21 .O 2.æ 26.0 1.67 (cribriform) L fronto-erhmoid attåchment (postcrior) cpp.l-ofaml mms n.2 2.5 6 6.1 -2.O4 6.9 -r.72 L fronto-ethnroid âttâchnìent (orbital) nrorl-ofaml nùfìs 35.6 2.5 6 28.5 -2.84 33.2 -0.96 't.7 R fronro-ethmoid attachnìent (anrerior) lc-cpar nìms 1.O l3 6 6.2 -0.62 0.54 R fronto-ethmoid attachrìent cpar-cppr mms 22.3 25 6 n.8 2- 25.8 1.40 (cribrifom) '7.0 R fronto-eLhnloid atLachnrent (posLcrior) cppr-ofantr rnJI'ìS 95 2.0 6 5.9 -1.25 R fronLo-ethmoi(l attachment (orbital) rnorr-ofamr rnms 35.2 34 6 29.3 -1;1 35.3 0.03 Sphenoid --t '7.6 L superior orbital fissure olarnl-sobl I nùns 129 1.1 6 64 -3.t2 Lfronto-sphenoidsuture(orbital) sobll-zisl mms 19.5 46 6 24.9 1.17 26.0 I .41 L lcsser wing lengLh spal-cppl I-IìIlìS 283 2.5 6 33. I t-92 21.3 -2 80

R su¡rcrior orbjtal fissu:c <¡l arn r-soblr nì[ìs ll8 3.6 6 6.0 1.61 1l.l -0.19 Iìlronto-sphenoidsLrturc(orbital) sobfr-z,fsr rrms 22.2 6.1 6 25.1 0.57 zo.2 -0.33 Il lesser wirg icngrh spâr cppr 307 25 6 31 .O 2.52 24.9 -2.32 Dimerrsio¡rs ClabclJar heighL g-n rrms 93 09 6 94 0.11 5.2 -4.56 0.35 GlabeUar prornirrcrrcc s !i mrììs 625 46 6 64.8 0 64.1 L ânterìor crarrial fossa tlepth sorl s¡;al Ûìn'ls 404 33 6 432 0 8.5 40.0 -o.12 lì antcrjor cranial lossa tlepLh sorr-spar nìflls 40.3 2.O 6 38.9 0 40.1 -0.10 Antcrior superior orbital u,itlth sorl-sorr Ûìnls 403 3.2 6 601 48. i 2.44 Anterior supcro-lat-craÌ orbital rv idtlr slorl-slorr nìt-lts flz 3 45 6 94.1 2.62 93.0 2.38 PosLerior rvidth spal-spar mnìs (Ã.6 44 6 11 .6 2.50 63.4 -0.13

A:ppendix 2 Page xli Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Years of Age (continued):

6 Ycar Standard Paticnt LW Patiónt AY

Anatomical Unit I)cfinition unit mcan srl n Valuc Z Valuc Z

ZYGOMATC BONE Distances L zygo-maxillary sulure (orbital) orl-iobfl mms 16.5 25 6 170 0 15.6 -0.36 '1 ,o.64 L inferior orbital fissure (ant height) iobfl-gwIl ì'ms ) 2.2 6 6.8 -0.I 5.8 L spheno-zygomaLic su[ìire zlsl-gwll mms 15.6 2.1 6 ll3 -2.05 15.4 -0.10 L fronto-zygomatic suture (medial) zlsl -s [orl mms I 1.3 1.5 6 l 3.9 1.73 13.0 l. 13 L fronto-zygomalic suture (anrerior) slorl-zfl nìms 1.3 0.9 6 107 3;t8 10.8 3.89 'tI -0.11 t.5 -o.32 L f ronto-zygomatic suture (laLcral) z[I-zfsl lììms 1.9 6 11 -0.24 L infe¡o-lateral orbiLaL rim orl ilorl ININS 13. r t] 6 t1 2 0 \2..1 L inferolateral orbital rim iìorl-lorl ¡NINS r 1.3 t't 6 9.3 -l I 8.9 -l 4l -0.07 L lateral orbiLal rim lo rl- s lorl nlilìs 4.8 15 6 10.8 4'l l- lateral frontal process zl'l-ztl rnnls l ti.-5 r.6 6 15 3 17.0 -0.94 L zygomatico-tempÕral suture ztÌ -pa rl ntrns 19.4 26 6 18.9 -0 I 25.3 2.2t 6 2.6.2 -0.51 27.8 -0.06 L lferior arch pa rl-zrn i I nìnìs 280 3.5 0.2'7 [- zygo-maxillary suturc z,ln il orl nìms 21.9 l5 6 11 3 -3 01 223 [ì zygornaxillary suture (orbital) orr-iobl r nìnls t62 2.1 6 t'7 9 0,63 r 3.9 -0.85 R inferior orl¡iLal fissure (anL heighL) iobl r-gu,lr nìnìs 70 226 12 0.09 6.6 -0.18 R spheno-zygomâtic suLurc g rvlr-z.ls r INII'IS 14.9 236 10.9 -t.14 13.4 -0.65 R fronto-zygomatic suturc (mediat) zl s r- slorr rnms l l.3 1.4 6 13.9 13.0 1.ZI R fronto-zygomatic suture (anrerior) slorr-zfr rîms 6.rJ 0.8 6 8.9 I 1.0 5.25 R fronto-zygomatic suturc (laLerat) zfr -zl sr tnms 8.3 t.3 6 9.0 8.1 0.31 R infero-lateral orbiral rin orr-ilorr ñults I 1.6 0.8 6 10.0 9.9 -2.13 R infero-lateral orbital rinr ilorr-lorr rnÍìs 12.3 1.1 6 l 0.1 -l 10.7 -0.94 10.6 3 4.1 -o.29 R lareral orbital rim I orr-slorr rnms 4.6 1.7 6 R lareral frontal process z[r-zLr mms 17.9 2.8 6 13.5 -l 16.6 -0.46 ll zygomatico-temporal suturc LLf-pà11 rnms 20.5 4.2 6 20.3 -0.05 23.2 0.& -0.68 Iì inferior arch PArr-zmlr tnms 29.1 5.0 6 28.5 -0.t2 25.1 Iì zygo-maxillary suture Lmt?of1 mfns 20.9 1.9 6 t] .1 -r.68 23.5 L37 D.imensions -o.31 L zygomatic height s lorl-zrnil rnms J J-õ 21 6 35.6 o.61 328 lì zygomaLic heighL slorr-z-nr i r ININS 86.2 4.1 6 92.O 123 93.3 I .51 L zygomaLic length parl orl [ìn'ìs 40.7 2.8 6 39 1 46 1 1.93 Iì. zygomatic length parr-orr ûìrns 41 4 45 6 40.8 -0 I 431 0.51 'r6.0 [- zygomatic lateral depth grvll-i lorl nlms 15.2 t4 6 05 l7 8 1.86 r r.29 L zygomaúc lateral depth g rvl r-i lorr Ûìrns 16.3 t.4 6 l 8.1 129 8.1

VOMEI{

I)ìsta n ces

1 39.8 1.81 PalataI lengrh arì s -prì s ntÛìs 36.9 1.6 6 44 Poslerior choanal height pns-h nìrns r9.l 28 6 16.8 14.0 - 1.82 Spheno-vomerine junctron h ves Ùìms 170 3.2 6 22.t 13.4 - 1.13 Ethmoid-vomerine junction vcs-vct IììNìS tz.6 4.4 6 t4.9 13.9 0.30 75.O -1.49 Septal attachrnent vg t -a rìs nìnìs 32.0 41 6 308 Dimension and Angle Vomerine length h-ans nìnìs 51.9 5.2 6 s83 4't.9 -o.77 6 20.2 -2.46 Vomerine angle s -n/h -an s d"g 23.4 1.3 202

Page xlii Crouzott Synd.rome Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Years of Age (continued):

6 Ycar Standard Paticdt LW Paticnt AY

Anatomical Unit Dcfinition unit mcân sl n Valuc 7, Valuc Z

ETHMOID Lateral Plate Dis!ances L anterior border lateral plate nlil-morl mms 143 1.6 6 ¿1. -t -).t 9;7 -2.8 8 L fronLal ethmoid attachment (orbital) lnorl-ofaml l'ms 35.6 2.5 6 28.5 -2.84 33.2 -0.96 -4.53 L posrerior border lateral plate ofamì-rnsl TTìIIì S I1.6 1.5 6 10.0 -1.07 4.8 -0.60 L i¡ferior border lateral platc rnsl-n l il mms 2tÌ 0 1.5 6 3l .0 2.N 2'l .r

R anterior bordcr laLeraI platc n li r-nrorr mms 14.1 1.8 6 9.3 -2.67 9.5 -2.56 ll frontal ethmoid attachrncnt (orbiLal) rn

R posterior border laLeral plate of ant r-rn s r nìrns t2.9 1.1 6 6.8 -3.59 4.8 -4.16 31 .0 27.9 0.r7 Iì inferior border lateraì ¡rlate rns r-ll I ir nìfn s 21 5 2.4 6 8.4 -0.65 l- fronral ethmoid attâchrnent (arrterior) rnorl-cpa I mms 9.1 2.0 6 li 9 L frontal ethmoid attachment (posterior) cppl -ofanr I mrns lr.2 2.5 6 6.1 6.9 -r.72 [ì frontal ethmoirl allachrnent (anLerior) rnorr-cpär rnrns 9.o 1.3 6 I1.5 l. 11.1 1.62 R fronral ethmoid attachrncrìl (¡rosLerior) cp p r-ofa rn r rfìm s 9.5 2.0 6 5.9 -1.80 7.O -1.25 Dinrensions

Posterior inferior widLh lns lr¡ s r nìÍìs 3l .0 296 21 I -t f4 25.'7 -l.83 21.3 Anterior rnferior rvidth n.lì l-n I ir mms 29.O 3.9 6 29'l 0.t8 -0.44 Anterior supcrior width rl

Posterior supcrior width ofam I -o fam r nìnìs 20.6 1.5 6 28.2 5.01 2,6.5 3.93 Ant lateral projection ol lateraI plarc nl i[-nrorì/nron-nI r deg 39.6 8l 6 31.3 -t.02 24.3 - 1.89 -3. o? -3.08 Post lateral projecLion of lateral ¡rlatc rl sl-ofaln l/ofarn r-msr d"g 538 14.3 6 8.1 15 Cribriform PIate Distances

L anterior cribrifonn platc I c-cpaÌ nùns 7.2 1.4 6 6.5 t -5 0.07 L lateral cribriform plato cpal-cppl mnìs 2lo 3.0 6 n.0 2.N 26.0 r.67 L posterior cribrilonn plate cs -cppl mms 62 0.9 6 9.3 3.44 10.7 5.00 Iì anterior cribriform plaLe fc-cpar mÍts 7.0 1.3 6 6.2 -o.62 1.7 0.54 R lateral cribrifomr plate cpa r-cPPr rlulls 22.3 2.5 6 n.8 2.20 25.8 t.40 lì posterior cribrifonn plate cs -cpPr mrns 6.1 l.l 6 8.7 2.36 8.2 1.91 r\nglcs L angle lateraJ cribrifon¡ plate cl SN s-n/cpa[-cppl d"g 56 32 6 lt I 1.8 0.69 R angle laLeral cribri[onn plate cf SN s rr/c¡rar-cppr dcg 3.5 1.8 6 125 5.0 0.83 Medial angle ol plaLc cl SN rr-s/cs-fc d"g 95 3;t 6 2.1 o1 0.05 Medial Platc I)istan ccs Antcrior height crisLa galli fc-cg Ûìms 6l 26 6 1.3 0.46 8.6 0.96

Posterior height crisLa gallì cll - cs r¡nìs 21 .8 3.8 6 23.4 0.42 20.3 -0.39 Spheno-cthrnoitl rnedial platc.iunction os -vcs rnms 14.9 1.2 6 l 3.5 -t 1'7 t4.4 -o.42 Dthrnojd-vomel inc jurtctirlt vcs-vot nìnìs 126 4.4 6 14.9 0.52 13.9 0.30 Septal attachlnetrL \rct-n mms 340 3.4 6 3t.7 -0.68 34.8 0.24 Nasal projccriolr rr-fc nìrns lt 6 1.5 6 8.2 -2.21 13.2 1.07 Dirnensions )'1 ) Maximum medial platc heighL vcr -c8 mnìs 30.8 z1 6 1.33 28.9 -0.70

Maximum medial platc lengLh tì -cs nìrns 333 4.1 6 37.6 1.05 3'7.9 1.12

Appendix 2 Page xliii Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Six Years of Age (continued):

6 Ycar Standnrd I'aticnt L!V Paticnt AY

Anatomical Unit l)cfÌnition unit mcan sd n Valuc L Valuc Z

SPHENOID I-esser Wing Dis tances L medial wing ofaml-acl mms I 1.8 0.9 6 I 8.1 7 13.7 2.rl

l- lateral wing (posLerior) a cl -spal mms ?o') 206 33.6 24.7 -2.25

L lateral wing (anterior) s pal -es mrns 346 ¿. 1 t) 4t3 31.9 - 1.00 R medial wing ofanl r-a cr rnrns tl 7 1.2 6 164 3. 13.2 1.25 Iì lareral wing (posterior) acr-sPar INNìS 28.5 3.5 6 37.0 243 24.8 -1.06

Iì latcral wing (anterior) 5l)är -us nt I ììs )6.3 3l 6 44.1 32.4 -t 26 Dirnensions Maximum lesser wing width spal -spar Ûìms 658 4.7 6 192 2.85 62.3 -o.14 l-esser wing superior angle spal-cs -spar d.g 139.1 9.2 6 135.8 -0.36 150.9 1.28

L lateral projecúon (anrerior angle) n -s/acl-spal ,1"8 54.5 52 6 14.1 311 49.3 - 1.00 [ì latcral projecúon (anLerior anglc) rr-s/acr spar d.g 56.0 4.5 6 1t 9 3.53 52.2 -0.84 l)tcrygoid PlaLe

[)is La nces L rnedial pterygoid plate pLst-hpl ûlrns 23.5 2.2 6 21.7 ì05 27.9 2m

L rnedial hamular nolch hpl -hn I ntÛìs 3.6 0.9 6 4.4 0.89 53 r.89 L lareral hamular notch hnl-pttl mms 94 2.4 6 9.9 o.21 8.9 -o.21

L lateral pterygoid plaLe ptllJ ool mrns 19.3 0.8 6 1 8.6 20.1 1.00 l{ medial pterygoid plate prsr-hpr rnms 23.1 Lt 6 21.1 tzl 23.2 0.09 R medial hamular notch hpr-hnr rnnìs 4.0 0.6 6 3.0 1.6 4.O 0.00 R lareral hamular notch hnr-pLlr rnms o, 1.6 6 94 0.1 9.9 o.44 R lateral pterygoid plate ptlr-foor rnr¡s 20.1 2.0 6 17.8 -1.1 19-3 -0.40 Angles L pterygoid axis n-s/ptst-hpl deg 60.3 4t 6 52.4 -1.9 57.2 -o.16 R pterygoid axis n-s/ptsr-hpr ,l"g 59. l 2.9 6 4'7 5 60. I 034 Greater Wing Distances La¡cral L anterior nliddle cranial fossa los l-grvLl nìnìs 36,0 296 36.4 014 39.8 L3l

L spheno-zygomaLic suture z.l sl-grvll rnnìs 15.6 2.t 6 ll3 -2.05 15.4 -0.l0 It anterior rniddle cranial fossa losr-g wlr ilìIns 343 4.2 6 31 1 0.81 37.4 0.74 Il spheno-zygornaúc suture grvl r-zf sr illnìs t4.9 2.3 6 10.9 -1.14 13.4 -0.65 OrbiLal [- inferior lareral orbital length gwil-grvrnl ININS 26.4 30 (¡ 23.5 -0.91 7<) -0.40

L superior orbiLal fissure height grvm l -sobfl nìms l',t .5 2'¿ 6 t'2.0 2 I'3.4 -l 8ó

[- spheno-frontal suture (orbitaì) sobl'l-2.[s I r lìnìs 19 .5 46 6 249 I tl 26.0 t.4t [ì. inferior lateral orbital length gw Ir-grvrn r rnnts 26.1 l6 6 239 I 25.4 -0.39 [ì. superior orbital fissure height grvnr r-sobf r nìilìs 15 9 32 6 l0.l l.8l 15.1 -0.06 [ì spheno-frontal suture (orbital) sobfr zlsr ftìnìs 22.2 6l 6 25 1 20.2 -0.33 Posterior

L spheno-peLrous temporâl suturc (in[) l osl-ptsl ilìnìs 14.0 o.1 6 149 13.2 -1.t4 R spheno-perrous temporal surure (inl) [osr-¡>tsr nìnìs 14 0 t.2 6 160 l?0 2.50 L posrerior middle cranial fossa fosl -peLal rnrns 18.9 l.l 6 24.4 24.6 5.1 8 6 40.2 t.3 41.1 1.78 I{ ¡rosLerior middle cranial fossa I os r-peta r Ûìnls 31.0 2.3

Page xliv Crouzon Syndroma Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndr

Six Years of Age (continued):

6 Yoar Standard Paticnt LW Paticnt AY

Anatomical Unit Dcfinition unit mcan S n Value Z Value Z

SPHENOID (continued) Dimensions and Angles

Posterior sphenoid width fos 1-fosr mrns 49.8 -t. -t 6 5t.2 0.42 53.8 1.21 L angle of greater wing splay zfsl-gwml-ptsl d.g 134.6 6.9 6 115.6 -2.75 1 10.3 -3.52 R angle of greatcr rvirg spla1, zfsr-gwm r-pts r deg 132.9 6.4 6 115;l -2.69 113.6 -3.02 Total angle of proLnrsiorr zfs[-gwrnl/gwm r-zfsr ,l"g 90.8 4l 6 tz9;7 8.28 120.3 6.28 lnferior greater wing protrusion gwll-gwnr [/gwrnr-gwlr d.g 94.2 45 6 l3l 8 u2.l 3.98

Posterior anglc ol greatcr wing los I -peta l/petar- los r d.g 956 107 6 80.7 r.39 86.8 -0.82 Squamous Sphenoid L squamous spheno-frontal sutrrrc zfsl-spcl nìnls 24.1 10 6 L squamous sphcno-parictal sururc spcl -sptl mms l0 I 25 6 L laLeral spheno-Lenrporal suturc [<>sl-sptl rnnìs .19 tì 2.2 6

R squamous spheno-frontal srrturc z-fs r-spcr mms 20.3 6.6 6

R squamous sphcno-parictal sutrrrc s PC r-sptr mms 8.4 3.0 6 R lateral spheno-ternlx)râl suturo [os r-sptr flìtlìs 41.3 31 6 Sphenoid l3ody Distances Lareral/Posterior llody, L anterior inferior lcngth gwrnl-ptsl mrns 1.5.9 t.t 6 20.4 2.65 21.1 3.06

r 4.0'7 L spheno-occipiLal synchondrosis (laL) 1;rs l-¡reLal Ûì ftì s tz.8 1.4 6 8.5 17.5 3.36 L posterior clinoid height pcLa[-pcl rnms 9..5 19 6 t2.8 7.74 12.3 t.41 Posterior clinoid width pcl-pcr flìÎls t4z 2.9 6 15.0 0.28 12.4 -0.62

R anterior inferior length gwmr-Ptsr fNINS r 6.9 2.O 6 2r.3 2. 20.3 1.70 R spheno-occipital syrrchondrosis (laL) pts r-peta r mrns 13.3 l5 6 18.0 3.13 16.5 2.13 R posterior clinoid heighL peta f-Pc r mr¡s 9.1 3.1 6 13.0 10.9 0.58 Anterior Body

L spheno-ethmoid sutu rc es -cppl nùÎs 62 0.9 6 9.3 10.7 5.00 L aoterior latera-l distancc cppl-olarnl mms |.2 2.5 6 6.1 6.9 -1.72 L anterior superior lerrgth ofaml-gwrnl mrnS 8.8 1.3 6 12.6 8.8 0.00

R spheno-etÌunoid sLlLu re cs-cppr rÌìms 6l l.l 6 8.7 8.2 r.9 r Iì anterior lalcral distancc c¡r¡rr-olarn r nrlì s 9.5 206 5.9 - 1.80 1.0 -t 25

R anterior superior lcngth ofam r-gwrn r nìnì s 9.2 13 6 10.9 1.3 I 1.6 -r.23 Sella

-J I J L .lateral anterior borl¡, cppl-of ¡rrl I n)flìs 13 6 15 6 155 1.n 8.9 L lzteral sella length of prnl-peLal mms 203 t4 6 21.7 1.00 25 1 343

R lateral anterior botl¡, cppr-of'prn r [ìftì s lz8 2.7 6 11.1 -0.50 1.4 -2 45

R lateral sella lcngth ofPnì r- l)ctä r nìnìs 2t.4 21 6 23.6 0.81 25.1 1.31 Basc/Floor []cd), Spheno-etlunoitl nretlial ¡rlate irrrtctiort cs -vcs Ûtnìs t49 1.2 6 13.5 l.t] t44 -o 42 Spheno-vomerinc jurrcrion VCS -h tnnl s I1 .0 t.2 Cr zz.l i.59 13.4 - l.l3 L posrerior width h-ptsl mnìs 14 tì 24 6 15.0 0.08 ))< 32r R posrerior widLh h-pts r tnms 136 3.3 6 t3-9 0.09 16. I u.;o

Appendix 2 Page xlv Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Six Years of Age (continued):

6 Yoar Standard Paticnt LW Paticnt AY

Anatomical Unit Dcfinition unit mean sd n Valuc Z Value 7,

SPHENOID (conrinued) Drmensions Anterior inferior body width gwrnl-gwmr mms 25.O l;t 6 25.1 041 26.6 o.94 Spheno-occipital synchondrosis (inf) ptsl-ptsr fnms 24.4 1.9 6 24.5 30. I 3.00 Anterior superior body widLh o[aml-ofamr mms 20.6 1.5 6 28.2 5 26.5 3.93

Spheno-æcipiral synchondrosis (sup) pcta ì -pcta r flìnìs 21.3 1.8 6 203 -0.56 20.9 -0.22

L posrerior body height pcl-ptsl nìms l8 r 36 6 28.0 2.15 25.9 2.17

[ì posterior body height l)c r-pts r nìrlìs 20.1 4.4 6 21 .8 1.15 23.3 0.13

L anterior body heighL ac [- g rvnr I nìÛìs l0 8 lr 6 t2.6 1.64 l0 7 -0.09 L anterior body height acf-gwnlr rnms I 1.5 1.0 6 tl 2 -0.30 10.9 -0.60 Angles Body floor angle es-ves-h d.g 121.6 6.0 6 I 14.8 -2.t3 t29.4 0.30 L lower body angle s-n/grvrn I-ptsl ,l"g 37.2 4.6 6 39.5 0..50 31.2 -1.30 R lower body angle s-n/gwmr-ptsr d"g 157.9 2.3 6 160.5 l.l3 158. I 0.09 L upper body angle s-n/ofprnl -peta I d"g 24.3 5.6 6 23.7 -0.11 8.2 -2.81

R upper body angle s -n/ofpm r-peta r d"g ))o 2.3 6 23.3 0. l7 14.0 -3.87

.IEMPORAL

Distances Squarnous

L lateral spheno-temporal suture I osl-sptl truÍs 49.8 2.2 6 L temporo-parieLal suture spLl-asl mms 16.9 '7.0 6 L occipital mastoid height asl-mal ÍtÍìs 31.1 3.5 6 I- rnedial mastoid prominence nral -srnfl rttrtìs I 1.5 1.3 6 151 3.23 16.2 3.62

R lateral spheno-temporal suture I osr-sptr mms 41.3 3.1 6

Iì temporo-parietal suture s ptr-a s r mrns 16.6 4.6 6 R occipital mastoid height asr-fnar mÍìs 38.6 2.8 6 R medial masLoid prominence mar-sml'r mÍìs I 1.6 08 6 I 1.4 13.0 1.15 Extemal Auditory Meatus (EAM) [- laLcral masroid prominence rnal-carniI nìms 16.0 3l 6 23.2 2 18l 0.68 L inferior-posrerior EAM rim eamil-e arn pl rnrns 66 2.6 6 18 0 10.8 1.62 L posterior-suporior BAM rirn cãnr pl'pol ITINS 6.2 1.8 6 55 10.0 2.ú L superior-anterior EAM rinr pol-eamal mrÌìs 5.6 1.0 6 4.1 -1.5 9.8 4.20 L anterior-inferior EAM nm eamal-e¿rnil mms 6.2 t.4 6 8.1 1.3 1.4 0.86 I{ lateral mastoid promìnence rnar calntr INIlìS 15.0 l.l 6 21.5 5.91 18.8 3.45 R inferior-posterior EAM rim eâmt r-eaûìpr mms 8.0 2-5 6 8.0 I1.0 1.20 R posrcrior-supcrior EAM rim cBmpr-por ITINS 7.4 18 6 5.7 o.94 7.6 0.1 I R superior-anterior EAM rirn por-câìnar mrns 6.3 ll 6 4.1 t1.2 4.45 R anLerior-i¡ferior EAM rim eantâ r-canìlr nùns 6.4 t6 6 13 0.56 13 0.56

Page xLvi Crouzon Syndrome Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Six Years of Age (continued):

6 Ycar Standard Paticnt LW Paticnt AY

Anatomical Unit l)clinition unit mcan sl n Valuc Z Value Z

TEMPORAL (conLinued) Zygoma L EAM-anicular fossa length eam al-afl mms 10.5 2.9 6 13.0 0.86 13.1 l.10 L articular fossa heighL afl-ael mns 12 l3 6 8.4 8.3 0.85 L inferior arch length ael-pa rl nìrÎs 13.8 3.3 6 9;l 8.4 -1.64 aal L zygomaLico-ternporal suture par[-ztl IîfNS 19.4 2.6 6 18.9 -0.19 25.3 L superior arch lengLh zLl-aul mms 346 3.4 6 25.6 34;l 0.03 Iì EAM-arLicular fossa length camar-afr fnfns ll5 14.8 14.0 f.i4 R aticular fossa height afr acr mrns 61 1.7 6 6.9 o.12 6.4 -0.1 8 R inferior arch length acr-Parr mms | ¿.J 4.6 6 8.4 -0.89 1.2 -i.15

R zygomauco-temporal suturc pa r r -'LLr mms 205 42 6 20.3 -0.05 23.2 0.64 R superior arch length '/,L1-Auf mrns 32.8 3.9 6 2't 5 -1.36 30.4 -o.62 Petrous

L spheno-petrous temporâl suturc (sup) [i s I -pctaÌ rnnls 16.8 1.5 6 19.5 1.80 2tl 2.87

L post-mcd ternlÐro-occipitâl sutrrrc ¡>cLal-jfpl IÌìTNS 293 266 30.3 0.38 34.1 1.85

L lateral tcmporo-occi¡rit¿l sLrturo iipl-asi I mrns 44 I 48 6

L pctrous superior rnargin as i I -petal mms 6tI 4.3 6

R spheno-pctrous Lernporal suture (sup) f isr-petâ r mms l8 r 0.9 6 20.2 2.33 t9.'l 1.78 R post-med temporo-occipital sutu rc peta r-.jlpr tntns 31 7 2.2 6 28.8 33.3 0.13

Iì ìateral temporo-occipi taI sutr¡ rc jfpr-asir mflìs ^a1 31 6

R petrous superior margin as r r- pcta r mms 61 6 2.0 6 L occipital mastoid st¡ture inferior rnal-jül rnms 18.0 2.5 6 25.8 3 26.2 3.28 L jugular foramen wjdth jfit-jfml ûùflS 13.1 3.0 6 Ú.2 -0.83 8.4 -1.'7'l L medial temporo-occipital suture (inf) jiml-pLsl nìms 19.4 1.8 6 25.2 '1, t.) 24.O 2.56

L spheno-¡rctrous Lcmporal suture (inf ) los l-pts I nuns 14.0 o.1 6 14.9 1.29 t3.2 -t.t4 (¡.0 a1 a R occipital rnasLoid suturc ilferior rna r-jflr ntrns 1 1.5 6 28-6 8.40 4.80

R jugular foramen width jllrjlmr ntrns 14. 1 2.9 6 3.4 -3.69 8.5 - 1.93

R medial temporo-occipital suture (in[) j lrn r-pts r tlùtì s 206 33 6 25.9 1.61 2.5.6 r.52

R spheno-petroLrs ternporal sLrture (irrf) los r- pts r rÌrns 14.0 l.z 6 16.0 t.61 17.0 2.50 Dimensions

L petrous ridge lengLh pcta I -pctpl mms 53.1 21 6 64.9 4.15 60.8 2.63

R petrous ridge lengLh Pet¿ìr-pctpr nìms 53.4 2.8 6 59.4 2.t 62.5 3.25 llLer-intenlal aud rncatus dir¡rcnsion iarnr-iarnl tÌtIns 4l .1 48 6 42.3 0.25 45.6 0.94

Ilìtcr-extemâl aucl nleatus dirncnsion pol-¡ror nìrn s 932 66 6 87.8 108.1 2.26 lnter-post jugular forarncn dirncnsion jlpr-jf pl fn[ìs 484 62 6 51 2 41.6 -0 13

lnter-mastoid d irncnsiorr rtal¡¡lar mfns 86.0 6.1 6 85.6 -0.06 89.6 0.54 Angles -1.31 Auditory canal anglc ¡rol-iarn I/ialn r-1xrr deg 1513 49 6 rst 1 0.08 t44.9 l)ctrous ridgc anglc pcr pl -p0t â l/pctä r-potp r d"g 97 lJ 8.8 6 852 -1.43 88.7 -1.03 0. 84.9 -0.89 [- zygorna projection angle ¡rcta I -a tr I -zl I d"g u89 4.5 6 9l;t R zygoma projcction arrglc pctar-äur 7-tr d"g 904 3.1 6 96.0 1.81 88.9 -0.48

Appendix 2 Page xlvtt Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Six Years of Age (continued):

6 Ycar Standard Paticnt LIV Patidnt AY

Anatomical Unit Dclinition unit mcan sd n Valuc Z Valuc Z

PARIE'fAL Dist¿nces Sagittal surure I trr mms 104.2 6.6 6 L parietal frontal (coronal) suturc br- spcl mms 89.3 5.0 6 L spheno-parietal suture spcl-sptl tnms 10. I 256 L temporo-parietal suture sptl -asl mms 16.9 1.O 6 L occipiro-parietal (lambdoid) suture as[-l rÌìms 82.4 5.8 6

R parieral frontal (coronal) su!ure b r-s ¡rc r rfìms 94.1 4.0 6 R sphcno-parietal suture 5l)cr sptr Inm6 8.4 3.0 6 R temporo-parietal suturc sptr-asr mms 't6.6 4.6 6 R occipiLo-parietal (lambdoid) suLure asr-l mms 84.tì 3.0 6

OCCU)TfAL Distances Lambdoid and Cranial Base

L occipiLo-parietal (lambdoid) sutLr re I -asl tnnls 82.4 5.8 6

L lateral tcrnporo-occipital suture (sup) ast-jll I nìnls 39.8 3.1 6

L lateral jugular lorarncn lf I l-jlpl nìilìs 12 l3 6 63 z6 -3.54 L mcdiaI jugular foramen jtpl-.jl rttl nìnìs 99 2.3 6 1.4 60 -1.70 l- rnedial tcuìporo-occipital suLurc (irrl) .jfrnl-¡rtsl rnÛìs t94 18 6 252 240 2.56 Iì occipiLo-parieral (lambdoid) suture l-asr MIIìS 84.8 30 6

R lateral temporo-occipital suturc (sup) a s r-jflr mtns 39.tì 1.6 6 R lateral jugular foramen jl'lr-jtpr tnms l.() 2.4 6 3.8 -1.71 4.2 t.54 R medial jugular foramen jfprjtrnr mms 10.9 2.1 6 6.5 6.4 t.67 l{ medial tcmporo-occipital suturc (iu[) j Im r-ptsr mms 20.6 3.3 6 25.9 l.6l 25.6 r.52

Inferior spheno-occipital synchond rosi s ptsr-ptsl rnnìs 24.4 19 6 24.5 30. l 3.m Forarnen Magnum

L anterior foramen magnum ba-ftn U mms 20.0 2.1 6 zo.4 0.1 22.5 l.l9 L posterior foramen m¿rgnum frnll o rnrns 24.0 4.5 6 21 .5 0.78 24.5 0.1I

R anterior foramen magnum ba-fin I r mms 20.6 2.3 6 ))< 0.83 22.0 0.61 R ¡rosterior forarnen magnum frn l r-cr rnnts 24.9 2.8 6 24.5 -0. l4 24.1 -0.29 Dimensions Foramen Magnum Foramen magnum length ba -o rrms 35.0 39 6 35.4 0l 31 .7 069 Foramen magnum widtÍ fnll l-l nrlr tntns 21 0 3.6 6 302 0.89 25.8 -0.33 Posterior Crarual Fossa Posterior cranial fossa depth o-roP lnINS 423 5.1 6 36.0 -t t7 50.0 1.43 Posterior occipiLaI height iop-l nìnìs 582 10.0 6 L ¡rosterìor fossa ìength pcLpÌ -iop nìrns 682 19 6 51 .9 69.0 0. t0 (r L posterior fossa length p(:l I r- ro f) Ûì r'tìs tf),6 4.1 60.0 -0 l3 68.2 1.62

Page xlviii Crouzon Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndr

Six Years of Age (continued):

6 Ycar Standard I'aticnt LW Patient AY

/t nato¡nical Unit Dcfin ition unit mcân d n Value Z Valuc Z

CRAMAL BASE SUTUIìES Anterior Cranial Fossa L spheno-ethmoid synchondrosis cs -cppl rnms 6.2 0.9 6 9.3 3.44 to.7 5.00 R spheno-etimoid synchondrosis es -cpp r mms 6.1 1.1 6 8.1 2.36 8.2 1.91 L spheno-frontal sutLtrc (anL fossa) cppl-spal mms 2'8.3 2.5 6 33. I 1.92 21.3 -2.80

R spheno-fronral suture (anL fossa) cpP r-s Pa r mlns 301 2.5 6 31 .O 2.52 24.9 -2.32

L spheno-frontal suture (orbita[) spa I -2,[s I mms 16.1 3.0 6 20.5 1.27 r1.4 o.23 R spheno-frontal suture (orbita[) spar-z[sr nìnìs t8.0 3.1 6 21 3 1.06 17.4 -0.19 L spheno-zygomatìc suture z[sl -gs,Ì1 mrrs 15 6 7.1 6 11.3 -2.O5 t5.4 -0. l0 R spheno-zygomatic suture zfs r-g rvlr mrìs 14.9 2.3 6 10.9 -r.14 t3.4 -0.65 Middle Cranial Fossa L spheno-squarnous tem¡roral sutu re gwll-fisl mms 35.3 226 34.5 -0.36 31.9 r.18 R spheno-squamous tcnlporal suture gwlr-fisr mms 34.1 2.7 6 35.4 o.26 36.4 0.63

L sphcno-petroLrs temporal suturc (sup) fi s [-pcta I ÍìINS 168 1.5 6 195 1.80 2t.t 2.87

R spheno-petrous ternporal strtLrre (sup) fi s r-peta r mÍìs l8.l 0.9 6 20.2 2.33 t9.7 1.78 L spheno-petrous ternporal suLurc (inl) fos l-ptsì mms 14.0 0.1 6 14.9 1.29 t3.2 -1. l4 Iì spheno-pctrous LernporaI suture (irr[) [osr-ptsr ntms 14.0 t2 6 16.0 1.67 17.0 2.50 Posterior Crarrial Fossa

L medial temporo-occipiLal suture (sup) pcLal-jlrnl NìINS 20 1 2.4 6 24.3 1.15 29.3 3.83

Il medial ternporo-occipital srrture (sr:p) ¡retar-j ftn r mms 20.5 296 z)t 1.10 z7.4 2.38

[- rnedìaI Lem¡rro

Spheno-occipital synchondrosis (in I ) ¡rtsl-ptsr t¡rms 24.4 t-9 6 24.5 0.05 30.1 3.00 L spheno-occipital synchondrosis (lat) pLsl-peLal mns 128 1.4 6 185 4.0'l 17.5 3.36 R spheno-occipital synchondrosis (laL) ptsr-pctä r mms 13.3 1.5 6 18.0 3.t3 165 2.t3

CRAMAL BASE Facial Heights

Anterior facral height n -BD nìm s 85.8 5.'7 6 r06.0 3.54 104.7 3.32 L postenor facial hcrght s-gol mfns 598 4.3 6 13.2 3.r2 64.5 l.09 '71.5 R postenor facial height s -gor mms 62.Z 4.4 6 2.11 65.9 0.84 Facial Angles SNA s-rì-ss d.g 810 3.9 6 18.9 -0.54 69.1 -3.05 SNB s-tì-sm deg t 5.t 4.2 6 724 -0.64 68.1 -1.52 Cranial Base Angle Cranial base anglc ba -s -rr d"g l33l 45 6 I18.0 -3.36 124.3 -1.96 Cranial Base Dimcnsions Cranial base lcngth ba-lr fnrls 829 51 6 860 0.54 85.6 0.41

Cìivus length (postcrior cranial basc) bas nlnì s 30.6 4.0 c 38.6 2.m 34.8 1.05 Anterior cranial basc lcrrgth sn rnnls 5lz 4.1 6 60.8 0.88 61.I 0.95

Appendix 2 Page xlix Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Adult:

,¡\dult Stantlard Paticnt HC l'ationt TS

Anatomical Unit I)cfi n i tion unit mcan sd n Valuc L Valuc Z

MANDIBLE Distances

L anterior superior body itl-en 1i.l mms 34.1 1.8 6 3 8.5 z.t1 36;7 l.l1 L posterior superior body crn I il-cbl tntns 21.0 2.2 6 24 I -1.32 28.5 0.68 L total superior body id-cbl mms 60.2 2.0 6 62.O 0.90 64.5 2.15 L anterior ramus cbl -cLl rrìrns 36.8 4.1 6 )oJ -1.85 45.1 2.t] L anterior mandibular noLch ct[-mnl nìilìs 11.9 4.1 6 15.4 -0.53 2t.l 0.68 L posterior mandibular norch rnnl-cdl nìms 19.4 2.8 6 't6.0 -1.21 2t6 o.19

L posterior ramus cd l -gol mms 5t.1 4.9 6 41.3 -2 I 61.0 1.90 L inferior body gol-grr mrÌs 80.2 4.O 6 12'7 -1.88 88.6 2.r0 lì anterior superior body id-em I ir mrns 34.8 2.0 6 31 I 1.55 34.8 0.00 R posterior superior body cln I ir-cbr rnrns 25.4 2.9 6 23-8 -0.55 28.0 0.90

R total superior body id -cbr rnrns -58 I 2.3 6 60. r 0.87 61.8 l.6t f{ anterior ramus cbr-ctr mms 37.f] 5.5 6 31.2 41.8 o.13

Iì anterior mandibular notch ctr-nt n r nìnts 19.0 4.1 6 14.4 -0.98 193 0.06

R posLerior mandibular notch rtt tt r-ctl r rnrììs 19.3 2.9 6 16.0 18.3 -0.34 Iì posterior ramus cd r-gor mIIìS 524 44 6 462 t 4t 60.4 t.82 R inferior body gor-8n Ûtllìs 804 4.9 6 740 131 85.5 104 [)inensions Iìtergonial dirnension gol -gor tntns 87.0 10 6 146 105.4 263

Intcrcondylar dirnension cd I -crl r nìilìs 114 3 13 6 95.3 I 10.7 -0.49 lntercoronoid base dimension cb[-cbr tnÛìs 173 l8 6 12.5 84.1 3.'78 lntermolar dimension ernlil-crnlir n'ìms 53.7 1.8 6 53.4 -0. I 53.4 -0. t7 L Superior ramus width cd[-cLl nìfns 30.6 2.6 6 25.9 -1.8 32.3 0.65 L inferior ramus width gol-ctrl NUìS 31.3 3.5 6 308 -0.1 31.1 r.6 Iì superior ramus width cdr-ctr rnms 30.8 2.8 6 263 l.6l 32.1 0.46 R inferior ramus widLh gor-cbr tnms 31.9 3.1 6 31 0 3',t .3 t.74 Anterior symphyseal height gn-id nìms 21.O 2.5 6 330 4t.5 5.80 L total mandibular length gn -ccll mms 116.4 6.2 6 105 5 -1 129.O 2.O3 R total mandibular length gn-cdr rnrns 115.6 6.3 6 I 10.6 -0 12t.3 0.90 Angles

L mandibular notch angle cd I -rn nl -cLl deg 103.3 1.5 6 I 10.7 98.5 -0.64

R mandibular notch angle cd r-r¡l rl r-ct r d"g 109.3 1.1 6 1 20.1 111 .2 1.03 L gonial angle c

L coronoid-dental base angle ctl-cl;[-crn I i I d"g I 18.3 5.4 6 136.2 3.3 1 119.4 0.20 R coronoid-dcntal base angle ctr-ctrr-cnt I ir d"g 't 16.1 5.5 6 t37 7 3.82 108.9 -1.42

L symphyseal angle gol-gn-id d"g 86. I 4.1 6 85.2 -0.22 8l .8 -1.05

R symphyscal angle gor-g rr - id d"8 84.9 3.4 6 8l .4 -1.03 84.1 -o.24 Anterior mandibular angle gol-gn -gor d"g 65.1 28 6 6tl -1 64 l4 5 314

I'age I Crouzon Syndromc Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Adult (continued):

Adult Standard Pat¡edt HC Patient TS

Anatomical Unit I)clî n ition unit mcân gl n Valuc Z Valuc Z

MAXILLA Distances Orbital Region L fronro-maxillary suture snrn [-morl rnrns t2.l 30 6 14.6 0.83 13.6 0.50 L frontal process orbital rim nlil-morl rtrns 151 2.6 6 10.4 -2.O4 t4.3 -0.54 L medial orbital floor r¡ sl-nlil mms 30.6 3.1 6 30.8 0.05 31.1 0.30 L posrerior lateral orbital l.loor rns[-iobfl INTNS 22.2 4.8 6 28.5 1.3 I 26.'l 0.94 L anterior lareral orbitaì floor orl-iobfl mtns 198 1.9 6 60 -1 15.0 -2.53 24.8 4.68 L maxillary infra-orbital rirn orlrrlil rnÍìs 13 1 25 6 23.'l R fronto-maxillar)¡ suture stìÛì r-fn orr mrns lt 4 t] 6 9.1 12.l 0.41

R frontal process orbital rim n lir-rnorr mns 166 z.t 6 15.2 11.0 -2.67 R medial orbital floor rnsr-n lir nìfns 32.4 3.6 6 30.4 29.t -0.92

R posterior lateral orbiLal lloor rn s r-iobfr mms 2t9 3.4 6 31 .0 2.68 25.2 0.91 14.0 -2.45 lì anterior lateral orbital f'loor orr- i ob[r mms Irì 9 zo6 2.6 -8.15 I{ maxillary infra-orbital nrn orr-nl ír rtms 13 5 3.2 6 20.3 2.10 28.8 4.80 Anrerior rJy'all [- anterior zygo-rnaxillaq, s¡¡¡¡¡s zm il -orl mms 255 45 6 20.9 22.1 -0.62 L lateral maxillar¡, v¿ll zrnil-crnlsl nìrns 250 5.1 6 22.3 -0.53 35.4 2.04 L anterior alveolar ntargitt crn I sl-pr ININS 39.0 206 32.2 3 32.8 -3.10 L lower pyrtfonn margin ans-alI lTtrns 17.0 1.5 6 16.0 I /.J o.20

1 o.5z L upper pyrilonn ntargin all-inrnl Ûì rns t] 1 25 6 21 1 .84 18.4 L naso-maxillarl, suture inrll-snnrI ûìnìs 20.t1 286 20.6 -0.07 26.8 2.14 - -1.41 [ì anLerior zygo m¿xillaq, suttrrc znì I r-orr mms 21 9 3.9 6 22.6 r.36 22.4

R lateral maxillaD, wall zmir-em I s r mms 25.4 54 6 24.9 -0.09 30.3 0.91 R anterior alveolar rnargirt crl I sr-pr mms 31 1 l8 6 30.5 -4.00 3 8.0 0.17 I{ lorver pyr.ifonn rnargin ans-alr nìms 16.5 l.t 6 15.7 -0;t3 11.3 o.73

R up¡rer pyrifonn rnargin a I r-inrn r mms r 5.8 2.6 6 22.4 2.54 t].l 0.50 L naso-rnaxillaq, sutu re tllÙ1 r-stìrn r mms 2t.o 296 21.8 0.28 21-7 2.31 Anterior alveolar height pr-â ns mrns t42 2.8 6 19.3 23.6 3.36 LateraI Wall

L posterior alvcolar nrargin cnl I slrnxtl nìnìs 23.0 2.0 6 20.9 - 1.05 21.7 2.35 L posrerior maxìllar¡, rvalì rnxtl¡rsl I.IìIl)S 418 42 6 43.6 043 60.5 4.45 L posterior [ateral orbital floor rns l-iobfl ûìms 22z 48 6 28.5 1.3 1 26.1 o.94 L posterior zygo-rnaxi ilar1, stttLt rc robfl-zmil nìn)s 230 2.3 6 22;7 -0. 13 24.r 0.48 R postcrior alvcolar rnargit: cn) I sr-rnxtr mrns 239 2.5 6 18.5 -2.16 23.4 -0.20 R posterior rnaxillaq, rvall rììxtr nìs r nùlì s 42.6 33 6 41 .3 62.1 5.91 R posterior latcral orbiLal Iloor rnsr-iol¡l r mrns 2t.9 3.4 6 310 2.68 25.2 0.91 0.50 Iì posterior z¡,go-rnax iJ la q, sutu rc iobf r-zrnir NÙTìS 238 2.4 6 20-9 1.21 250 Palate L posterior palatal hcighL crn I sl-gpfl TììfIìS 25.3 1.4 6 21.3 24.2 -0.79 L posterior palaLal rvidth gpl'l-pns nìnìs 16 5 11 6 159 -0.35 t'7.1 0.35 R posrcrior palatal hcighL crn lsr-g¡rIt Intns 21 | r4 6 20.9 -4.43 25.O -1.50 [ì posterior palaLaL rvi

Appendix 2 Page li Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Adult (continued):

Atlult Standard I)aticnt HC Paticnt TS

Anatomical Unit l)clîni tion unit nlcan sd n Valuc Z Valuc Z

MAXILLA (conúnued) Dimensions

Anterior midline height n -pr mms 59.5 3.9 6 66. I 1.69 74.9 3.95 L lateral height nror[-em I sì mms 54-5 3.2 6 59.2 I 4'l 69.0 4.53 R lateral height nrorr cm I sr mms 56.2 2.9 6 63.6 2.55 695 4.59 L posterior height gpfhnsl rnms 33.4 33 6 35.3 058 45.8 3.16

R posterior height gp [r-rn s r rnms 33.5 2.6 6 40.2 2.58 45.1 4.46

L supcrior lengtb msl-inrn I nìms 41.6 3.8 6 52.1 Ll8 53.0 1.42 R superior lengtb rììs r-t tìrn r mrns 47.3 3.3 6 195 o.67 50. I 0.85 Posterior palaLal widtl gpfl -gpir ilì[ìs 31 2 276 30.2 -0 37 33. I 0.70 Anterior inter-cani¡e width ecsl-ecsr ìtìms 351 l9 6 3 5.9 0.1 I 34.6 -0.58 Maximum maxillary widLh ztl iI-z-rnir flìnls 95. l 9.6 6 19.1 -t.61 99.0 0.41 Superior (urLcr-orbital rim) width orl-orr Ûìnìs 65.tì 2.8 6 64.tt 19.1 4.96 Nasal aperture height rìâ-â¡ls ilìnìs 30.8 21 6 29.5 22.6 -3.04 Nasal apenure width :ill-alr mtns 26_3 1.5 6 ')t o 24.4 -t.27 Angles

l- orbital floor angle n Ii I rnsl-iobfl clcg 53.0 10.4 6 433 -0.9 62.4 0,90 Iì orbiLal floor angle nlir-r¡rsr-ioblr dcg 52.9 12.0 6 39.7 -l.l 72.9 t.6'l L ¡xrsrerior inferior angle rnsl-gpl'[-crn I sl dcg I 17.5 6.8 6 121 .8 L5l l 18.9 0.21 ll posterior infcrior angle nrsr-gpfr-crn I sr d"g l167 iÌl 6 1158 -0.1 I I13.6 -0.38 Supcrior rnaxilIar¡, splay iol¡fl -rnsl/rnsr-iobl r d"g 9l I 10.0 6 124 -l 87 103.5 1.24 l- superior /occlusal angle srrrnl -rnsl/crn I sl -pr d"g 33.8 4.1 6 46.8 3.17 29.3 - 1.10

[ì superior /occlusal anglc snrn r-rns r/crn I s r-pr ,iog 34.4 J- 1 Ò 31.0 079 35.2 o.24 L palatal/occlusal angle ans-pns/ern I sl-pr d"g 4 8.rJ 2.t 6 54.1 252 46.3 - 1,19 R palatal/occlusaI angle arrs-pns/crn I sr-pr d"g 50.0 266 5l .l o.42 52.5 0.96 Ânterior palatal angle gpl[ arrs-gp1'r dog 4t.3 266 426 050 31 .5 -t.46 Maxillary arch angle gpfl-pr-gpl-r d"g 31.9 226 44.8 314 41.9 1.82

NASAL BONES I)is rances

Nasal length tì â -tl tnnìs t6.1 23 6 22.6 2.51 32.1 6.96

L inferìor nasal width n a-inlrt l Ùìms ll.l 22 6 69 -l 9l 8.3 -t.21 L naso-maxillary suture inm l-snml mrns 208 28 6 20.6 -0.07 26.8 2.14

l- fronto-nasal suture rr -sn r¡rl Ûìnìs 6u ltÌ 6 6.2 -0.33 8.0 0.61 R inferior nasal width rì¿t ilìÛìr IilÙìS I 1.4 2l 6 95 8.6 - 1.33

R nasornaxillary suture r rìrn r-srìrìì r nìÌìs 2l.o 29 6 2t 8 0.28 21.7 2.31 lt fronto-nasaI suLure tì-stìnìr nìrns 17 t9 6 77 8.4 0.37 Dimensions Infcrior width inrnl innrr [ì [ls 16.3 25 6 Il -l 84 12.8 - 1.40 Superior width srrrnl -sn rrl r Ûìnìs 10.7 3.0 6 9.2 I r.0 0. l0 Ànglcs Nasal/anterior cranial base anglc s-n-tìâ d"g r08.9 5.9 6 973 8'7.9 -3.56

Superior nasal bone anglc snrtt I -n -s rlrn r ,l"g l0l 6 205 6 tìl 5 -0.9 84. I -0.85 Inferior nasal bone anglc inrnl-na innrr d"g 88.4 8.9 6 rì9.8 0l 985 1.13

Splay ol nasal b<.¡nes i n rn l -srl¡r l/sn ll r-i n rn r ,icg 160 12 6 75 -l I 4.O -1.61

Page lii Crouzon \'yndromc Appendix 2 Measurements for the Experimentar Standards and the patients with Crouzon Syndrome:

Adult (continued):

Adult Standard Paticnt HC Paticnt TS

Anâtomical Unit Dcfinition unit mcan d n Value Z Value Z

FRON'IAL Distances Supra-orbital L fronto-nasal sulure n-snml mms 6.8 I.8 6 6.2 -0.33 8.0 0.67 L fronto-maxillary surure snml-morl mms t2.t 3.0 6 t4.6 0.83 13.6 0.50 L superior medi¿l orbiral rim nrorl-sorl mms 194 2.7 6 24.3 1.81 18, I -0,48 L superior lateral orbital rirn sorl-slorl mms 29.8 1.5 6 31 .8 1.33 41.4 1.13 Lfronto-zygomaric sururc (anLerior) slorl-zfl mms 85 t4 6 8.8 o.2t 9.2 0.50 LfronLo-zygornaricsurure(Ìateral) zl'l-2,îsl tnms ll I 2.3 6 6.4 -2.04 8.0 -1.35 Lfronto-zygomalicsururc (nredial) zlsl-slorl lnrns 12.5 38 6 6.5 - 1.58 8.1 - 1.16 Iì fronto-nasal sutrìre n-stìmr mms 7.7 19 6 7.1 8.4 o.37 R fronLo-maxillar)/ sLrturc snrnr-rnorr mnts 11 .4 1.1 6 9;7 L2.l 0.41 Il superior medial orbiral rirn nìon-sorr mms 203 2.0 6 24l 22.7 1.20 [ì. su¡rcnor lateral orbital rirn sorr-slorr mns 30.5 l.-5 6 30.8 o.20 37.8 4.81 I{ fronto-zygornatic suturc (anLerior) slorr-zfr mJns tì.3 ll 6 9.1 t.2l 9.3 0.91 R fronto-zygomâric suture (lateraL) zlr-zfsr mms 10.8 2.7 6 8.3 -0.93 8.8 -o.74 lìfronto-zygorrìaricsuture(mcdial) z.fsr-slorr mms I 1.5 2,8 6 9.8 -0.61 90 -0.89 Ethmoid Nasal roor projecrion n-lc llms r 6.0 2.O 5 9.8 3.1 18.7 1.35 L fronto-ethmoìd arLachmcnr (anterior) lc-cpal o') mms 2.0 5 7.6 16. I 3.45 L fronto-erlunoid aLrachrncnt cpal-cppl (cribriform) nìms t8 7 r.9 6 26.6 4.16 118 -3 63 L fronto-erhmoid atrachntent (ltosLerior) c¡tpl-ofarnl tnrns t3.9 t.9 6 t.5 -3.47 19.9 3.1ó L fronro-erhmoid arrâchnìent (orbitat) rnorl-of ar¡ll tnÙìs 31 9 09 6 29.O -9.89 38.1 0.22 R fronto-ethmoid attachnrcnL (antcrior) fc-c¡rar nillls 8.9 r.3 5 6.3 -2.00 15.5 5.08 R fronto-ethnloid attachnìcnt cpar-cppr mtns 165 (cribriform) 2.9 6 25.9 10.3 -2.14 R fronto-ethmoid attâchrnent (posLerior) cppr-ofarnr mfns 14.9 1.1 6 83 -3.88 19. I 2.4't R fronto-ethmoid aLtachmenr (orbiral) rnorr-ofamr mms 368 r.8 6 309 -3.28 35.3 -0.83 Sphenoid L superior orbiral fissure ofarnl-sol>fl Ûùns 12.1 3.3 6 6.1 -r.82 16.6 1.36 Lfronto-sphcnoidsurure(orbiLal) sobll-zisl mm5 26.2 3.3 6 31.3 1.55 25.6 -0. 18 L lcsser rving lengrh spal-cppl mms 320 45 6 28.3 -0.82 36.3 0.96 Iì superior orbiral fissurc ofanrr-sobfr nìrns 10.2 2.3 6 1.5 14.4 183 Rfronto-sphenoidsururc(ortriral) sobfr-z[sr mms 28.3 4.0 6 25.4 0 25.5 -0.10 R lesser wing lengLh spar-cl)pr tÎ¡ts 33.2 2.4 6 30.6 1.08 38-7 ))o I)imensions

Glabellar heighL g-rì [ìJlìs 85 2.6 6 I 1.9 1.3 1 6.6 -o.73 Glabellar promirrerrcc s-g mnts 7l 0 39 6 68.8 -0.56 68.6 -0.62 L anterior cranial fossa tlc¡rth sorl-s¡tal nìrns 44.2 3.9 6 36.8 - 1.90 43.'t -0. l3 Iì anterjor cranial fossa dcpLh sorr-spar mÍìs 45.3 2.8 6 34.5 -3.86 43.2 -o.15 Anterior superior orbital rvidth sorl-sorr rìlrns 478 236 58.0 443 48.9 0.48 Anterior supero-lateral orbrtal rvidth slorl-slorr nùns 962 236 98.2 0.81 I 13.3 143 Posterior rvidLh spal-spar nìms 690 39 6 81.5 3.2r 86.8 4.56

Appendix2 Page li¡i Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Adult (continued):

Adult Standard Paticnt HC Pat¡cht TS

Anatomical Unit Dclinition unit meân sd n Valuc Z Valuc Z

ZYGOMA'fIC BONE Distances L zygo-rnaxillary sulure (orbital) orl -iobfl mms l 9.8 1.9 6 6.0 -1 15.0 -2.53 L inferior orbital fissure (anL heìghL) iobfl-gwlJ nìms 10.0 1.8 3 122 I 5.3 -2 6l L spheno-zygomatic suture zl'sl-gwll mtns 12.4 0.9 3 220 l0 20.9 9.44 L fronto-zygomatic suture (medial) zf sl-slorl tnlns r2.5 3¡Ì ó 65 -l.5 8.1 - 1.16 L fronto-zygomatic suture (anLerior) sl orl-zfl rnrns 85 t4 6 88 o2l o) 0.50 L fronto-zygomalic suture (laLeral) zll-z[sl fnms I l.l 2.3 6 64 8.0 - 1.35 L infero-larcral orbital rim orl-ilorl mrns 13.4 2.0 6 il,4 I 1.3 -1.05 L infero-lareral orbital rinr ilorI-lorl rnrns 13.5 2.6 6 10.9 15.9 o.92 L lateral orbital rim lorl- slorl fruns 7.8 3.3 6 58 -06 6.7 -0.33 L lareral frontal process zf1-ztl mms t?o 1.9 6 zt.l 20.9 - 1.58 L zygomatico-temporal suture ztl-parl ûìms 23.3 1.4 6 238 0 26.4 2.2r L inferior arch pa rl- zrnil ûrms 31.2 1.5 6 29.6 30.6 -4.40 I- zygo-maxillary suture zmil-orl Íìms 255 4.5 6 zo.9 22.7 -o.62 Iì zygo-maxillary suture (orbiLal) o r-iobf r rnms 18.9 2.0 6 26 -8. I 14.0 -2.45

Iì i¡ferior orbiral fissure (ant height) iobfr-g w I r mms l0 0 2.6 3 l6.l 2.3 5.1 -1.88 I{ spheno-zygomatic suture grvlr-z-[sr mnìs 14.5 15 3 19 3 t9.1 3.4'l

Iì fronto-zygomatic suture (medial) zls r- s lorr nìrns I 1.5 2.8 6 9.8 -0.61 9.0 -0.89 R fronto-zygornadc suture (anterior) slorr-zfr tnlns 8.3 l.l 6 9.1 t2 9.3 0.91

R fronto-zygomatic suture (laLeral) zk -z[ sr mms l 0.8 2.1 6 õ. J 8.8 -0.74

R infero-lateral orbital rim o rr- i lorr llùns I 1.5 2.5 6 10.9 -0 10.9 -0.24 R infero-lateral orbiLal rinr ilon-lorr mms t2.5 2.6 6 14.0 0.58 16.0 1.35

R lateral orbital rim I orr-s I orr tnms 6.9 3.3 6 7.2 0.09 58 -0.33 [ì lateral frontal process tl'r-zt¡ ntftìs 243 l8 6 18.2 339 20.3 -2.22 [ì zygomaLico-temporal suLure zLl -Pa I I nl nìs 22.1 25 6 264 148 2'l .0 112 [ì infcrior arch PArr-znìlr mms 35.3 2.1 6 30.5 315 -1.81 R zygo-maxillary suture zrn I r-o rr mrns 279 39 (r 226 136 22.4 -1.41 Dimensions

L zygomatic height s Iorl-zrn il rlìfns 40.8 2t 6 40.5 -0. l4 44.0 1.52 R zygomatic height slorr-zrnir ÛìIls 101.8 6.0 6 91 .2 o.-Ì'7 1r4.9 2.18 L zygomatic lengrh pa rl-orl nìtìs 50.9 42 6 4l .l -2.33 43.0 - 1.88 R zygomatic length PAr( ort mms 49.2 f.36 45.4 -t. l5 43.1 - 1.85 L zygomaúc lateral depth grvll-ilorl mms t6.4 16 3 106 -3.62 15.4 -o.62

L zygomaúc Ìateral depth g rv I r-ilo rr nìms 11.6 ll 3 12.3 -4.82 11 .4 -0.1 8

VOMER Distances

Palatal length arìs -Prì s rnrns 46.9 4.6 6 43.0 -0.85 5r.3 0.96

Posterior choanal height ¡rrrs-h nìms 22.8 2.2 6 20.5 -l 05 20.2 -1.18 Spheno-vomerine juncrion h -vcs nìrÌìs I 8.8 226 I 8.4 -0.l8 13.8 -2.2'7 Erhmoiä-vomerine junction ves-\,el nìms 20.9 6.4 6 56 -2.39 18.1 -0.44 Septal attachment \icl-âtìs nìnìs 33.3 6.6 6 347 o.2t 34.2 014 f)imension and Angle

Vomerine length h -ans [ì Ûls 64.1 4.2 6 5 3.3 2.11 60.8 -0.93

Vomerine angle s -n/h -an s d"g 20.4 3.2 6 21 .4 2.19 29.3 2.78

Page liv Crouzon Synd.rome Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Adult (continued):

Âdult Standard Paticnt HC Paticnt TS

Anatomical Unit Dcfinition unit mcån sd n Value Z Value Z

ETHMOID Lateral Plare I)is tances

L anterior bordcr lateral p/aLe nlil-morl rtrns t5.l 266 10.4 -2.04 14.3 -o.54

L frontal erhmoid attâchrnenL (orbiral) morl-ofam I mm5 31 .9 0.9 6 29.O -9.89 38.1 0.22 L posrerior bordcr lareral plare olaml-msl nìms t4.1 31 6 7.6 -1.92 5.1 -2.43 L inferior border lateral plare rnslnlil mms 30.6 3.1 6 30.8 0.05 31.7 0.30 R anterior border lateraI plare n lir-¡norr mms 166 2.t 6 15.2 -0.67 1 1.0 -2.67 R frontal erhmoid allachmenr (orbiral) lnorr-ofanl r mÌns 36.8 1.8 6 30.9 -3.28 35.3 -0.83 R posterior border lareral plate ofalnr-msr mÍts 12.6 2.9 6 60 -2.28 5.4 -2.48 R inferior border lateral plaLe msr-nlir mrns 32.4 36 6 30.4 29.1 -0.92

L frontal ethmoid arrachmerìr (anLerior) rn orl -cpa I NìINS 133 1.6 6 9.1 12.9 -0.25 L frontal ethmoid attâchrìenr (posLcrior) cppl-o[aml mrns 13.9 1.9 6 I -5 19.9 3.16 R fronral ethmoid anachnìent (anLerior) rnorr-cPar fnms 12.1 206 85 -2.1 r5.8 1.55 R frontal ethmoid attachrnerìr (posrerior) cpp r-ofamr Itìrns 14.9 t] 6 8.3 -3.88 19. I 2.41 Dimensions 1 Posterior i¡ferior rvidrh lnslrn s r MIIS 409 4.6 6 28.3 40.7 -0.04 Anterior inferior rvidLh nlil-n lir mrlìs 39.4 3.5 6 30.3 36.3 -0.89 Anterior superior widLh lno rlrnor mms 23.5 1.3 6 24.2 0.54 28.9 4.t5 Posterior superior rvidLh ofam l-olam r nùns 261 2.2 6 29.1 1.09 337 3.18 Anr lateral projecrion of laLeral plarc n lil-morì/rnorr-nlir d"g 5t4 9.2 6 n.l -3.29 33.9 -2.55 Post lateral projcction of lateral plare ms [-otam l/ofam r-msr deg s3.6 11.8 6 15.5 -3.23 83.9 2.5'7 Cribriform Plate Distances

L anterior cr-ibrilonr ¡;larc I c-cpal mms 92 2.0 5 1.6 -0.80 16 I 3.45

L lateral cribrìfonn plaLc cpa l -cpp I tnr¡s 18.7 1.9 6 26.6 416 I 1.8 -3.63 L posLerior cribrifonn plaLc cs -cppl nìms 6.4 1.7 6 13. r 3.94 8.4 l.l8 R anterior cribriform plare I'c-cpa r mms 89 1.3 5 6.3 -2.O0 15.5 5.08 R lateral cribrifonn plate cpa r-cPPr ìnms 165 z.<) 6 2s.9 3.24 10.3 -2.t4

R posterior cribrifonn ¡rlaLe es-cppf mrns 7.1 1.8 6 12.8 3.1 8.3 0.6't Angles

L angle laLeral cribrifonr plaLc cl SN s -nlcpal -cppl deg 8l 5.4 6 I 1.9 0 28.9 3.85 R angle lateral cribrifomr plare cf SN s-n /cpa r-cppr deg 5.4 4.8 6 21.1 3.2'7 34.8 6.12 Medial angle of plate cf SN n-s/es-fc deg 192 33 5 3.6 -4.13 23.6 t.33 Medial Plate Distances

Anterior hcight crisra galìj lc-cg mrÌs 4.2 5 8.4 l.9t tô -1.00 Posterior height crisLa galli cg -es tntns 21.8 2.0 6 20.1 -0.85 21.9 0.05 Spherro-ethmoid rncdial plarc jurrcriorr cs-ves mtns 21.8 1.6 6 21.7 -0.06 266 3.00 Ethmoid-vomerinc _jurrcrion vcs vot mrns 20.9 6.4 6 56 -,) 20 18. I -o.44 Septal attachmenL vol -n fllllìs 396 40 6 46.2 L65 58.2 4.65

Nasal projection n-fc lÌìÛl s 16 0 2.O 5 98 -3.10 18.7 1.3 5 Dimensions

Maximum nrcdial plaLe hcighL vcr -cg tnrns 39.6 3l 6 35.7 -t -26 53.1 4.55 Maximum media[ plaLc lerrgLh n -cs nìllìs 358 39 6 366 o.2l f6.9 o.28

Appendix 2 Page lv Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Adult (continued):

Adult Standard I'aticnt HC Patiõnt TS

Anatomical Unit f)ctinition unit mcan sd n Valuc Z Valuc Z

SI'HENOII) Lesser Wing

Dis ta nccs L medial wing olanll -acl mms 15. I 1.4 6 14.3 9.1 -3.86 l- lateral wing (posterior) acl-spal mms 28.5 2.6 6 343 223 39.3 4. r5

L lateral wing (anterior) s ¡>al -cs rnnìs 365 3.9 6 40.8 44.O 1.92 R medial wing ol anlr-acr rNIììS 15.6 r.3 6 t52 -0.31 1t.7 -3.00 R lateral wing (¡rosterior) acr-sPar NìINS 29.0 z.o 6 31 .9 30. I 0.55 R lateral wing (anterior) sPilr cs tììInÌ 38.E 726 43.3 2 44,1 2.68 l)imensions

Maximum lesser wing width s pal-spa r rnms 69.1 3.3 6 8r.3 86.3 5.21 Lesser wing superìor angle spal-cs -spar ,1"8 129.0 14 6 150.1 r53.3 3.28 L lateral projecrion (anterior anglc) n-s/acl-spal deg 54.1 8.3 6 59.2 0.61 51;l -0.29 R lareral projection (anterior angle) n-s/acr-spar d.g 568 5.6 6 56.2 -0 ll 51 .8 0. t8 Pterygoid Platc

I)i s ta nces L medial pterygoid plaLe ptsl-hpl rnnìs 30.6 3.3 6 26.1 -t f6 31 .6 2.12 L medial harnular notch hpl-hnI nì[ìs 5.2 1.8 6 43 -0 50 6.4 o.67 L lateral harnular notch hnl-pLll nìms 10.0 1.6 6 9.6 -0.25 13.2 2.00 L lateral pterygoid plate ptl,l-1ool mrns 26.O 236 20.0 -2.6t )'l 't, 0.51 I{ medial pterygoid plaLe pts r-h pr ntms 304 226 26.3 -1.86 33.1 t.3z R medial hamular notch hpr-hnr Ûìnls 5.8 2.5 6 4.6 -0.48 4.6 -0.48

R lateral hamular notch h n r-¡;tl r nlms 10.4 25 6 lll 0.28 t3.4 1.ZO R lareral pLerygoid plate ptlr- loor rlìnìs 243 24 6 20.6 21.0 I .13

,A,rrg lcs

[. pterygoid axis n -s/pLsl-hpl .lcg 61 1 34 6 83.4 638 19.5 5.24

fì pterygoid axrs n -s/pts r-hpr dcg 60.6 3.1 6 86.5 8.03 79.9 623 G reater Vy'ing Distances Lateral L anterior middle cranial fossa fosl-gwll rnrns 42t 2.9 3 38.6 t.2l 45.4 1.14 L spheno-zygomaúc suture zl sl-grvll trms 124 0.9 3 22.0 2.09 9.44

R anterior middle cranial fossa fos r-g rvlr tÌìrns 39.6 2.1 3 38 1 -0.71 43.8 z.m R spheno-zygomatic sutt¡re grvlr-zls r rnrns 145 l5 3 19.3 t9.1 J.41 OrbiLal

L inferior lateral orbital length grvll-grvrn I llìflìs 30.5 21 3 28.3 -0 8l 24.6 -2.19

L superior orbital fissure height gwml-sobfl rllrllS r 5.5 42 6 14.0 -0.3 15.7 0.05 [. spheno-f rontal suture (orbiLal) sobf[-zfsl ININS 26.2 1t 6 31.3 25.6 -0.1 8 ll inferior laLeral orbiLal length gwlr-gwrn r nìrns 29.o 28 3 23.8 25.0 -1.43 R srrperior orbital fissure heighL grvnr r-sobfr rnrlìs 13.4 44 6 -0.2'l 18.8 t23

Il spheno-frontal suture (orbital) sobl r-z.l s r nìnìs 28.3 40 6 254 -o.tz 25.5 -0.70 Posterior L spheno-petrous tenrporal suLurc (inf) losl-ptsl nì nìs 14.4 l8 6 15.3 0.50 t 4.6 011 R spheno-petrous temporal sLrLure (inf) fosr-pts r nìnìs t5 0 z.t 6 17 0 0.95 15.2 0.10

L posterior rniddle cranial fossa [osl -peLa I nì r'lìs 225 l0 6 259 3.40 263 3.80 R posterior lniddle cranial fossa fos r-¡rcLa r Ûìnìs 43.8 1.6 6 42.5 -0.8 I 41.9 i.l9

I'age Lvi Crouzon Syndrome Appendix 2 Measurements for the Experimental standards and the patients with Crouzon Syndrome:

Adult (continued):

Adult Standard Paticnt HC Paticnt TS

Anatolnical Unit Dclìnition unit mcan d n Valuc Z Value Z

SPHENOID (conrinued) Dimensions and Angles Posterior sphenoitl witlLh l'osl-[osr nìrn s 58.3 2.3 6 52.3 -2.61 57.1 -0.52 L angle of grcarcr wing spla)/ zls[-gwml-pLsl d"g 135.t 5.1 6 1 30.1 -0.9 140.3 t.02 R angle of grearer wing splay z[s r-gwm r-pts r d"g 136.1 6.0 6 140.2 136. I -0.10 Toral angle of protrusiorr zlsl-gwrn l/g wnr r- zfs r d"g 89. r 5.5 6 105 5 3.1 106.5 335 Inlerior greater rving protrusiorr grvll-grvnt l/gwmr-g wlr dcg 87.6 34 3 121.O 122.5 t0.26 Posterior angle ol grcatcr wirrg fosl-pcLa l/pera r-[os r d"g 92.9 7l 6 - 1.86 94.1 0.28 Squamous Sphenoid L squamous spheno-fronLal surure z-fsl -spcl tnms 21 .6 6.4 5 L squarnous spherro-parieral srrture spcl-sptl mms U5 235 L lareral spheno-tcmporal sururo losl-spLì mms 52.2 2.6 5 R squamous spheno-frontal suture zfsr-spcr MS 26.8 4.8 5 R squamous spheno-parictal srrrurc spcr- sPtr ITtr'Iì S 10.3 2.1 5 R lateral spheno-temporâl suturc fos r-sptr mrns 51 8 33 5 Sphenoid Body Dislan ces

Lateralfi osrerior 13

L anterior itr[erior lengLh gwnr l-prsì mms 2tt 2.8 6 2l.1 0.00 3 1.5 31t L spheno-occipiral syrrchonclrosìs (laL) ptsl-petal mfns 16.2 19 6 17.7 o.79 I 5.8 -o.2r L posrerior cliroid heighL pcLal-pcl rnms 12.0 3.2 6 12.9 0.28 r 0.8 -o.37 Posterior cL¡oid widrh pcl-pcr mms 159 1.7 6 14.8 I ó.5 0.35 R anterior Lrferior lerrgth 8wnìr-ptsr nìrns 19.5 2.5 6 2t.6 29.9 4.16 Iì spheno-occìpitaI s¡,nchonrlrosis (laL) ptsr-pcrar mns t5.9 2t 6 11.2 15.8 -0.05 R ¡rosrerior clinoid hcighr Pctâ r-pc r mms 120 30 6 14.4 0.80 t2.6 0.20 ArrLerior BorJy

L spheno-etfunt¡id suLr¡ rc cs -cppJ Ûùns 64 tl 6 r3.t 3.94 8.4 l.r8 L anterior lateral distarrcc cppl-ofaml rnms 139 1.9 6 '7.3 19.9 3.16 L anterior su¡rerior lcngrh ofaml-gwrnl mrns 9.5 2.2 6 t2.8 '7.5 -0.91 R spheno-ethrrr)id suturc cs-cPpr ruI'ts l1 1.8 6 12.8 3.17 8.3 0.67 R anterior lateral disLance cppr-ofam r mms 14.9 11 6 8.3 -3.8 8 19. 1 2.47 R anterior superior lengrh ofamr-grvm r lnms Il 1.4 6 14.0 1.64 8.3 -2.43 Sella L lareral anrerior bod), cppl -olprn I mfns t] .t 21 6 12.3 ))o 19.8 r.29 L lateral selÌa lcngrh o[prnl-pct al nìrns 233 t.7 6 24.7 23.1 -0.12 R lateral anterior bod), cppr-ofpÛì r mûìs 19.2 226 12.0 -3.21 19.9 0.32 R lareral sella lengLh ofprn r-pctar mms 245 206 28.9 2.20 27.6 1.55 Base/F1oor Ilody Spherro-cthmoitl nrcrlial plarc jrrrrcriorr cs -ves nìms 21.3 1.6 6 21.1 -0.06 26.6 300 Spheno-vornerìrrc juncLion vcs-h mÌìs 18.8 2.2 6 18.4 -0.1 r 3.8 aa1 L posterior widrh h -ptsl nìms 16.1 1.4 6 I 3.5 ))a 205 2.71 R ¡rosrerior widLh h -pLs r tlìÙìs 11 I 14 6 13.5 2.51 t].l 0.00

Appendix 2 Page lvii Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Adult (continued):

Adult Standard Paticnt HC Patient TS

Anatomical Unit Dcfinition unit rncân sd n Valuc L Valuc Z

SPIIENOID (continued) Dimensions Anterior inferior body width gwlnl-gwmr mrns 331 21 6 30.6 -l l5 42.0 3.O'7

Spheno-occipiral synchondrosis (ì nf ) ¡rtsl-ptsr mms 29.t\ 2.1 6 23.9 -2.81 29.1 -0.33

Anterior superior body widLh ofam [-o[arn r rnms 26.1 2.2 6 29 1 1.09 33.1 3. 18

Spheno-occipiLal synchon

L upper body angle s -n/ofpnr l-peLa I dcB 261 5.8 6 22.3 -o1 8.6 -1.12

R upper body angle s -rr/ofprn r-pcta r dcB 21.4 4.9 6 l1 6 -2.o0 14.9 -2.55

'fEMPORAL I)istances Squamous L lateral spheno-temporal suture fbsl-sptl mtns 52.2 2.6 5 L remporo-parieLal suture sptl-asl nt¡ns 80.2 7,8 5 L occipiral mastoid height asl-mal rnms 486 93 6 L medial masLoid prominence mal-sr¡fl rnms I.5.8 2.1 6 12.4 -l 22.6 2.52 R lareral spheno-lemporal suturc [osr-s ptr nìIns 5l.8 3.3 5 Iì temporo-parietal suIure sPtr-asr rnÌìs 83.6 44 5 R occipital mastoid heighL äsr-Ûìar rnms 50.5 6.2 6 [ì rnedial mastoid prontinence rrtar-slnf r nìnìs 15.6 40 6 14 I -0.3 24.8 2.30 llxtenral AudiLory Meatus (EAM) L lareral rnastoid prominencc nral-carnil mrns 20.9 2.t 6 28.6 3.67 L inferior-posterior EAM rirn earnil-earn pl tnrns 88 1.9 6 9.1 0.41 L posrerior-superior EAM rim campl-pol mrns 6.8 0.9 6 1.0 0.22

L superior-anterior EAM rirn ¡>ol-earnal mrns 6.4 1.0 6 6.2 -0.20 L anrcrior-inferior EAM rirn eamal-earnil rnflìs 6.3 o.1 6 4.9 -2.00 R lateral mastoid prominence ûìar-canìlr rnms 20.4 2.4 6 234 26.8 2.61 R inferior-posrerior EAM rim eârnt r-earnpr Inms 1t;l 1.6 6 8.9 -1.75 8.3 _) 1) -1.00 -0.86 R posrerior-superior EAM rim c arn D r-po r mms 75 Q] 6 6.8 6.9

R superior-anterior EAM rirn PO r-eânì â r rnÍìs 6.5 0.1 6 4.6 -211 10 0.11 _) 11 I{ anterior-inferior EAM nm catnA r-eaÙl r Ùì Ûìs 6.8 l.l 6 1.o 018 43 '

Page lviii L'rouzon Synd.romt: Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Adult (continued):

r\dult Standard Paticnt HC Patlent TS

Anatomical Unit l)cfin ition unit mcan S n Valuc Z Valuc Z

TEMPORAL (continLred) Zygoma

L EAM-anicular fossa lengrh camal-afl tntns t2.5 14 6 14.2 1.21 L articular fossa heighr afl-acl mms 9.0 2.t 6 1.6 -0.61 8.4 -0.29 L inferior arch lcngth ael -pa rl TTUnS 14.8 2.3 6 t'7.4 1.13 t2.5 -1.00 L zygomatico-Lcrnporal su [u re parl-ttl m¡ns 233 t.4 6 23.8 0.36 26.4 2.21 L superior arch lerrgth zLl-àul mrns 44.5 28 6 36.3 -2.93 41.3 -t.14 Il EAM-artrcular lossa lengLh eamar-a f r ntnts t2.o t2 6 12.5 o.42 t3.7 1.42 R anicular fossa heighr al r-acr mms ft.9 2.3 6 8.0 -0.39 9.3 0.11 Iì i¡ferior arch length aer-parr mms l4 t 3.0 6 14.2 0.03 10.8 -1.10 R zygornatico-temporal suturc pa I r -7,Lf trìlns 22.7 t< a 264 27.0 1.72 R superior arch lcngth zLr - àlr rnms 4t4 1.-5 6 40.7 -o.47 40.8 -0.40 Petrous

L spheno-petrous temporâl surure (sup) lisl-peLal nìnìs 19.8 t.9 6 19.8 0.00 22.t 121 L post-rned temporo-occipital sutLrre petal -j f¡rl mms 33.5 13 6 3l .8 -1.17 30.8 -2.08 L lateral temporo-occipitäl suru re jlpl-asil fnms 41 I 51 6 L peLrous superior rnargin asil-pctal rnnìs 648 5.9 6 R spheno-petrorrs ternporaI suLrrre (sLrp) [isr-pcta r rnms 20.2 0.5 6 16.8 -6.80 2t.6 2.80 R post-med temporo-occipital su[u rc peta r-j Ip r llms 36.0 1.5 6 34.5 - 1.00 35.4 -0.40 R lateral temporo-occipital surure jþr-asir mms 41 3 2.9 6 R petrous superior rnargin asrr-pctar mms 6ó.0 4.7 6 L occipital masLoid suture fitferior mal-jfll mms 26.O 2.1 6 32.6 2.44 36.8 4.00 L jugular foramen widrh jfll -jtnr I nìms 134 4.8 6 4.6 -1.83 10.2 -0.61 L medial tem¡xrro-occipirat suLure (inl) jfrnl-ptsì r¡nìs 21.5 5.1 6 32.6 2. l'1.5 -0.78 L spheno-petrous tenìporâl suLLrre (inf) fosl-pLsl nilÎs 14.4 1.8 6 15.3 t4.6 0.1I ll occipiLal ¡¡asroid suLurc infcrior rna r-j fl r mrns 23.1 3.5 6 25.8 o.7'7 26.3 0.91 jugular R foranrell widLh jil rjfnr r mms t23 2.3 6 8.t - 1.83 13.7 0.61 R medial Lem¡xrro-occipiral surure (inf ) jfrnr-pLsr mms 25.3 54 6 3r.8 1.20 25.1 -0.04 Iì spheno-pctrous tcnìporal sLrrrrrc (irrf) fìrs r-pLsr Ilì n'ìs r5.0 2t 6 170 0.95 15.2 0.10 I)imensions

L petrous ridge lengrh pcLal-petpl mrns 54.9 6.0 6 &.9 t.67 78. I 3.87 R petrous ndge lelrgth peta r-PetPr rnms 570 3.9 6 5'7.7 0, l8 74.6 4.51 Inter-intemal aud rncatr¡s dintcnsiorr iant r-iarl I fnlns 43.8 3.6 6 35.6 -2.28 45.3 0.42 Inter-extemal aud [ìeatus dilncnsiolt ¡rol-por nìms 103 1 2.O 6 101.4 -0.85 110.7 3.80 jugula Lrter-post r foramen dirnen sion jiprj|pt rÌùns 5.5 l 24 6 5l .5 -1.50 51.8 1.13 I¡ter-mastoid di¡nensìon lna l¡na r û1ìns 99t 51 6 86.5 -2.41 t06.'7 1.49 Angles

Auditor¡, canaì attgle pol-ianrl/iarnr-¡xrr deg 152 3 5.7 6 I 33.8 3.25 t45.6 -1.18 Petrous ridge anglc pcLpl-peLal/peLar-pctpr d"g 861 3.8 6 85. l 84.8 -0.50 L z5,gona projecLion anglc pctal-aul-z-LJ deg 88.7 46 6 79.5 83.7 - 1.09 R zygorna projecLion angle peLal-avt-ztr d"g 902 4.6 6 79.1 -2.41 87.4 -0.61

Appendix 2 Page lix Appendix 2 Measurements for the Experimental Standards and the Patients with Crouzon Syndrome:

Adult (continued):

Adult Standard Paticnt HC Paticnt TS

Anatomical Unit Dcfinition unit mcan sd n Valuc Z Valuc Z

PAzuETAL Distances

Sagirml suture l-br rnms I 08.8 4.0 6 L parietal frontal (coronal) suture br-s pcl mms 86.4 1.6 5 L spbeno-parietal suture spcl-sptl mms I 1.5 2.3 5

L temporo-parietal sutu re sptl-ä s I Dìrns 80.2 78 .5 L occipito-parietal (lambdoid) suturc asl-l Ûìflìs 141 33 6

R parietal frontal (coronal) sutLrrc br-spcr rnms 9l .5 60 5

[ì spheno-parietal suture spcr-sptr tntts r 0.3 21 .5 Iì Lerlrporo-parieLal suture spÍ-àsr fnms 83ó 44 5 l{ occipito-parietal (larnbdoid) suLurc asr-l rnrns 764 48 6

OCCIPITAL Distances L¿mbdoid and Cranial Base

L occipito-parietal (lambdoid) suLurc I -asl mrns 741 3.3 6 L lateral temporo-occipital suturc (sLrp) as l-j fÌ I nìrns 459 6.4 6 L la¡eral jugular foramen inl-jfpl Itìnìs 1.1 2.9 6 68 -0.3 l 58 -0.66 L medial jugular foramen jfpl-jl"rnl rnms 10. I 47 6 5.1 -l 06 5.2 - 1.04 L medial temporo-occipital suture (inf) jfrnl-pLsl [ìt¡s 21.5 5.1 6 32.6 2.1 8 t].5 -0.78 '16.4 R occipito-parietal (lambdoid) suLure l-asr ININS 4.8 6 R lateral temporo-occipital suture (sup) asr-jflr INNìS 440 3.4 6 l{ lateral jugular foramen jftrjfpr ntms 8.5 14 6 8.1 0. l4 8.8 0.21 R lnedial jugular forarnen jl prjfnr r rnrns 10.0 3.4 6 8tì -0.35 5.8 -t.24 R medial temporo-occipital suture (inf) jfmr-ptsr rnms 25.3 54 6 31.8 1.20 25.1 -0,04 Inferior spheno-occipital synchondrosis pLsr-ptsl rnrns 29.8 2.1 6 23.9 -2.8 I 29.1 -0.33 lìoramen Magnunr

L anterior foramen magnum ba-fmll mrns 19.8 2.8 6 2t.3 0.5 26.O 2.Zt I- posrerior foramen magnum lnrll -

R posterior foramen magnurÌ f rllr o ftìnls 235 33 6 255 0.61 26.1 0.19 Dimensions lìorarnen Magnurn

Foramen magnum lengLh ba -r¡ tnfns 32.8 4.2 6 33.9 0 39.8 1.61

Foramen magnurn width fl¡tll-frnlr nìrns 28.3 1.8 6 25.9 -1.33 3 3.0 2.61 Posterior Cranial Fossa Posterior crarúal fossa depth o-lop nlllls 42.8 2.9 6 31 .5 -1.83 49.1 2.38 Posterior occipital height ropl IllINS 50.2 4.O 6 L posrerior fossa lengrh pe pl- op rnms 59.1 5.4 6 51.1 -0.3'7 12.3 2.33 L posterior lossa length pctpr-roP nì tns 64.3 5l 6 51 .t -l 4l 63.6 -0.14

Page lx Crouzon Syndrome Appendix 2 Measurements for the Experimental Standards and the Patients with

Crouzon Syndrome:

Adult (continued):

Standârd Paticnt HC Patient TS ^(lult

Ä.natomical Unit I)clìn ition unit mcan sl n Valuc Z Value Z

CRAMAL BASE SU-t'UIìES Anterior Cranial Fossa L spheno-ethmoid synchondrosìs cs-cppl mms 6.4 1.1 6 13.1 3. 8.4 1.1 8 R spheno-ethmoid synchondrosis es-cPpr mms 7.1 1.8 6 12.8 3.1 8.3 0.67 L spheno-frontaI suture (ant fossa) cppl-spal mms 32.O 4.5 6 28.3 36.3 0.96 R spheno-frontal suture (ant lossa) cPP r-sPa r mtns 33.2 2.4 6 30.6 - 1.08 38.'7 )10 L spheno-frontal suture (orbital) spal-zfsl tnms )) () 41 6 20.0 -0.62 r4.0 -1.89 R spheno-frontal suLurc (orbita[) spar-zfsr mms 224 4.0 6 13.1 -2.32 2t.1 -0.32 L spheno-zygomatic sutu re z[sl-gwll mms 12.4 09 3 220 10.67 20.9 9.44 R spheno-zygomatic srrtu re zls r-g rvl r mms 14.5 1.5 3 19.3 3.20 19;l 3.41 Middle Cranial Fossa

L spheno-squamous ternporal suturc grv ll -f is I Ílìms 40.5 J.I J 36.2 1.39 42.5 0.65 R spheno-squamous temporal suture grvl r-frsr runs 38.6 223 35.6 40.5 0.86 L spheno-petrous temporal suture (sup) fisl-pctal Inms 19.8 1.9 6 19.8 22.1 1.21 R spheno-petrous tonìporal suLure (su¡r) fisr-petâr mms 20.2 0.5 6 16.8 21.6 2.80 L spheno-petrous tcnr¡roral suLure (irrl) los[-ptsl mms 14.4 I.8 6 15.3 r4.6 0.1I R spheno-petror:s temporal suttrrc (inl) fos r-ptsr mms 15 0 21 6 t] .o 0.95 15.2 0.10 Posterior Cranial l;ossa 0.41 [- medial tonìporo occi¡>ital sLrturc (su[)) ¡rcLal jlrnl nìfns 24.3 4.6 6 29.3 1.09 26.2 Iì medial tempor<>-occipiLal srrtLrrc (sup) ¡rctar-j I rn r mnls 25. tt 39 6 2l .o 0.31 30.5 1.21 -0.78 L medial tem¡rro-occi¡rital sutLrrc (inl) j lìn l -¡>Ls I mlns 21.5 5l 6 32.6 2.t8 17.5 R medial temporo-occipiral suLLrre (in[) jl rn r-pts r ININS 25.3 54 6 31 .8 t.20 z5.t -0.04 L occipital mastoid suture (su¡nrior) jfll -pctpl mms 34 1 5.8 6 39.1 0. 50. I 2.66 R occipital mastoid su[ure (superior) jfl r-petpr mms 3'7.1 3.1 6 32.6 -1.45 47.7 3.42 Spheno-occipital s),nchondrosis (st¡p) pctal -pctâ r rffns 24.5 1.2 6 20.7 -3.r7 19.6 -4.08 Spheno-occipital synchondrosis (in i) pts l-pts r mms 298 21 6 23.9 -2.81 29.r -0.33 L spheno-occipital synchondrosis ([at) ptsl-pcLal mms 162 1.9 6 17.7 0. 15.8 -0.21 R spheno-occipital s¡,rrchondrosi" (lat) ptsr-pela r Ìntns 15.9 2.1 6 11.2 15.8 -0.05

CRANIAL I]ASE Facial HeighLs

Anterior facial hcight rì -gn l"ms 104 8 6.8 6 125.9 3.10 139.0 5.03

L posterior facial hcight s -gol mrns 84..5 7.0 6 80.8 -0.53 93.8 1.33 R posterior laciaì hcight s-8or nìrns 81 .4 69 6 78.9 -1 23 98.'1 1.64 Facial Angles SNA s-rì -ss dcg 85.8 5.r 6 634 -4.39 64.6 -4.16

SNB s -rì -snì d"B ti0.3 39 6 r)t.t -3.23 65.8 -3.72 Cranial Base Anglc Cranial base anglc ba -s -n d"g 126 6 5.2 6 139 8 2.54 140.9 2.75 Cranial Basc I)irncnsions Cranial base lerrgth ba-rt mnìs 100 I 74 6 95.6 -0.61 98.7 -0. 19 Cììvus lcngth (¡rostcrior cranial basc) lr¿ -s ûìms 430 2.1 6 39.9 -1. l5 3 8.8 - 1.56 cranial basc lcngth s-n nìrns 676 f] 6 61.6 -1.62 65.5 -o.57 ^ntcrior

2 Page lxi Page lxii Lrouzon Sttndronrc Appendix 3

Measurements for Thrce Dimensional Quantitative Analysis of the Surgical Morphology in Crouzon Syndrome

The surgery of five patients was analysed and included: l. Patient SH Fronto-orbital Advance

2. Patient JS Fronto-orbital Advance

3. Patient IP Fronto-orbital Advance

4. Patient LW Extended Fronto-orbital Advance

5. Patient HC Fronto-orbitâl Advance

Three comparisons of the surgery were undertaken: a) Pre-operative Surgical Unif. vs Standa¡d Surgicat Unit b) Pre-operative Surgical Unit vs Post-operative Surgical Unit c) Post--operalive Surgical Unir vs Srandard Surgical Unit Appendix 3 Results of Three Dimensional Quantitative Analysis of Surgical Morphology:

Patient SH Fronto-orbital Advance:

a. Prc-operativc Surgical Unit vs Standarrl Surgical Unit

Landmarks Landmark Diffcrcnccs (mrn) x (right) y (anterior) z (supcrior) Magnitudc superior orbirale left -2.4 2.8 -l 1.0 11.6 superior orbitale right -5.6 -o.2 -13.6 l4;l supero-lateral orbitale superius left -4.2 0.1 -t2.0 t2.1 supero-lateral orbitale superius righL 1.0 -0.1 -1 0.1 lo.2 supero-medial orbitale left -2.3 0.3 -13 3 13.5 supero-medial orbitale right -2.8 11 -14.7 15.I zygo-f rontale superius left -5.3 -1.0 -9.5 11.0 zygo-frontale superius right 28 -0.8 -80 8.5

Displaccmcnt (nrnr) x (right) r(antcrior) z(supcrior) Magnitudc I | | _)o 0.3

b. Prc-opcrativc Surgical Un¡t vs Post-opcrativc Surgical Unit

LHndnrarks Lanrlmurk l)ilTcrcnccs (mln) x (right) y (antcrior) z (supcrior) Nlagnitudc superior orbitaÌe lefL -0.8 0.1 4.1 4.8 superior orbitale right 39 4.t 8.1 9.9 supero-lateral orbitale superius left 4.6 4.5 t2.l t3.7 supero-latera-l orbitale superius righ L 2.8 41 ll.l 12.3 supero-medial orbitale left -t4 -0.5 6.9 1.1 supero-medial orbitale right 1.7 1.9 8.9 9.3 zygo-f rontale superius left 14 1.9 1.2 13.8 zygo-frontale superius righL zl 5.9 9.0 I 1.0

Translation of Pre-operativc Surgical Unit Displaccmcnt (mm) to Post-operativc position x (right) y (antcrior) z (supcrior) Magnitude mm

c. Post-opcrativc Surgical Unit vs Standard Surgical Unit

Landmarks Landmark Diffcrcnccs (mrn) x (right) v (antcrior) z (su pcrior) Magnitude superior orbirale left -5.3 1.6 -3.6 10.0 superior orbitale right -4.0 98 -2.6 10.9 supero-lateral orbitale superius left - 1.5 9l 1.9 10.0 supero-ìateral orbitale superius right 2.3 9.4 5.-t to.z supero-medial orbitale left -5.9 5.2 -4.2 8.9 supero-medial orbitale right -3.5 6.3 -4.0 8.2 zygo-frontale superius left -5.6 10.5 2.5 12.2 zygo-ironLaIe superius right 3.6 9,1 2.8 l0.l

'l'ranslation of Post-opcrativc Surgie:rl Urrit Displnccmcnt (rnrn) from thc Standard Surgical Unit x (right) y (antcrior) z (supcrior) Magnitudc

TruN

Page lxiv Crouzon Syndrome Appendix 3 Results of rhree Dimensionar euantitative Analysis of surgical Morphology (continued):

PatientJS Fronto-orbital Advance:

a. Prc-opcrativc Surgical Unit vs Standard Surgical Unit

Landmarks Landrnark Difl'crcnccs (mm) x (right) y (rntcrior) z (supcrior) Magnitude

superior orbitale lefi -0. I -4.3 3.4 5.5 superior orbitale righL 0.0 -4.1 3.1 5.1 supero-laLeral orbiLalc supcrius left -27 -62 r.9 7.0 supero-lareral orbiLale superius rìghr 1.1 -4.9 0.1 5.0 supero-medial orbinle lefi -l 6 -2.O 5.5 6.1 supero-medial orbirale righr 1.0 -1.8 4.4 4.9 zygo-fronrale superius lefL -3 I -6.1 0.9 7.4 zygo-fronrale superius righL 11 -48 0l 5.1

Translation of Prc.opcrativc Srrrgical Unit I)isplaccrncnt (mrn) from thc Standartl Surgical Unit x (right) y (antcrior) z, (supcrior) Magnitudc rnm

b, Prc-opcrativc.Surgical Unit vs Post.o¡tcrativc Surgical Unit

[,andmarks Landnrark Ditfcrcnccs (mrn) x (right) y (antcrior) z (supcrior) Magnitudc

superior orbitale IeIL 3.0 10.5 3.1 1 r.5 superior orbirale righL 0't 6.6 2.5 1..1 supero-Ìateral olbitale superius Lcfr 3.2 16 0 5.2 t'l.l supero-lareral orbiLale superius righr 0.0 9'I -l 8 9.9 su¡rerornedial orbirale lefi o.7 7.2 4.9 8.7 supero-medial orbirale righL 1.4 71 5.6 9.6 zygo-frontale supcrius lefr -0.7 l1 .6 6.1 18.6 zygo-frontalc supcriLrs ri ghr 0l r 0.6 0.0 10.6

'I'ranslation ol' Prc-opcrativc Surgical Unit l)isplaccrncnt (mm) to Post-opcrativc position x (right) y (antcrior) z (supcrior) Magnitudc mm

c. Post.opcrativc Surgical Unit vs Stantllrd Surgical Unit

Landrnarks Lanrhnark f)ifl'crcnccs (rnrn) x (right) v (antcrior) z (supcrior) Magnitudc superior orbitale lefL 2.6 6.1 J.t 9.2 superior orbitale righL 04 3.1 3.6 4.8 supero-lateral orbirale superius lolt 0.1 10.0 6.0 tl.7 supero-lateral orbitale superius righL 0.8 52 -3.4 6.3 supero-medial orl¡itale lelL -t2 5.6 8.8 10.5 supero-medial orbiLale righr 2. I 6.3 83 10.6 zygo-frontale superius lelL -4 I 1r.l 6.0 13.3 zygo-frontale supcri rrs ri ghL t.5 t- I -1.1 6.5

'Iranslation of Post.opcr:rtivc Surgical Unit l)isplaccrncnt (mrn) fro¡n thc Standartl Surgical Unit x (right) y (antr:rior) z (supcrior) Magnitudc ûÌm

Appendix 3 Page ln Appendix 3 Results of Three Dimensional Quantitative Analysis of Surgical Morphology (continued):

Patient IP Fronto-orbital Advance:

a. Prc-opcrativc Surgical Unit vs Standarrl Surgical Unit

Landmarks Land¡nark Dif[crcnccs (nrm) x (right) y (antcrior) z (supcrior) Magnitudc

a< superior orbirale left -6.8 -18.6 ^ 32.2 superior orbitale right 16.2 -19.3 23.5 34.5 supero-lateral orbirale superius left -5 1 -t.-t 15.4 18.0 supero-lateral orbiLale supcrius righL 13. I -t2.8 12.5 22.2 supero-medial orbitale left -0.5 -10.3 18.4 2t.r supero-medial orbitale right 8.9 - 10.6 19 I 23.6 zygo-f rontale superius left -80 -6.8 t6.9 19.9 zygo-frontale superius right i -5.4 -12 3 t9't z't.9

Translation of Pre-opcrativc Surgical Unit Displaccrncnt (nrrn) from thc Standard Surgical Unit x (right) y (antcrior) z (su¡rcrior) Magnitudc

b. Prc-opcrativc Surgical Unit vs I)ost-opcrativc Surgical Unit

Landmarks I andmark l)iffcrcnccs^ (rnnr) x (right) y (antcrior) z (supcrior) Magnitudc superior orbitalc Ìefi -5E 19.5 4.4 20.8 superior orbitale right -2.0 24.1 45 24.6 supero-lateral orbiLale superius lolL -1 .5 13z r5.4 20.8 supero-lateral orbitale superius right 00 19.0 t93 27 -O supero-medial orbitale left -3 1 19.9 u5 23.3 supero-medial orbitale right ll3 20.6 t4.t 2't.4 zygo-f rontale superius left -43 il.1 15 1 19.1 zygo-frontale superius right -l 3 t6.4 12.3 20.5

Translation of Prc-opcrativc Surgical Unit Displaccrncnt (rnnr) to Post-opcrativc position x (right) r,(antcrior) z (supcrior) Magnitudc mm

c. Post-opcrativc Surgical Unit vs Stanrlard Surgical Unit

Landmarks Landmark Diffcrcnccs (rnm) x (right) y (antcrior) z (supcrior) Magnitude superior orbitale left -10 7 4.7 33.2 35.2 superior orbitale right r5 9 6.6 30.3 34.9 supero-lateral orbitale superius left 8.7 8.7 321 34-9 supero-lateral orbitale superius right 14.2 6.6 33.5 31 .0 supero-medial orbirale lefi -2.5 12. I 32.1 34.4 superornedial orbitale right -0.6 l 1.8 34.9 36.9 zygo-frontale superius lefi -r0 9 1.5 344 36.9 zygo-lronLale superius right r5 6 .5.3 334 31.3

'l'ranslation of Post-opcrativc Surgical L.tnit I)isplacclncnt (nrtn) (right) (untcrior) z (r-upcr¡or) l\{agnitudc fro¡n thc Standard Surgical Unit x | .v | | rtl 328 33.6 mm

Page lxvi Crouzon Syndrome Appendix 3 Results of Three Dimensional Quantitative Analysis of Surgical Morphology (continued):

Patient LW Extended Fronto-orbital Advance:

a. Prc-opcrativc Surgical Unit vs Standard Surgical Unit

Landmarks Landmark Diffcrcnccs (mm) x (right) y (antcrior) z (supcrior) Magnitudc infero-lateral orbitale left -3.8 -4-5 -2.1 6.2 infero-lateral orbitalc nghL 4.8 -26 -4.6 7.1 orbitale zygomaLrc left -4.8 -4.4 -3.6 7.5 orbitale zygomatic right 8.6 -3.2 -3.0 9.6 pre-articulare left -1.5 -2.3 -2.3 3.6 pre-aniculare righL 2.1 -4.1 -3.4 6.4 superior orbitale left -55 4.5 -2.3 7.5 superior orbitale right 15.9 t.z -2.8 t6.2 supero-lateral orbitale lefr -5.3 -0.9 1.0 5.5 supero-lateral orbiLale right 8.4 -l I - 1.0 8.5 supero-medial orbitale left -1.3 5.4 -3.5 6.6 s upero-medial orbitaLe right 3.6 5.9 -4.1 8.0 zygo-Irontale left -4.5 -4.6 0.1 6.4 zygo-frontale righr 8.2 -4.6 -2.9 9.9 zygo-maxillare i¡ferius laterale lefr -0 I -3.7 0.0 3.1 zygo-maxillare inferius laLerale nghr 03 -24 0.0 2.4 zygo-temporale lef t -2.6 -6.0 4.6 8.0 zygo-ternporale right õz -5.4 1.1 8.4

'franslation of Prc.oporativc Surgical Unit Displaccrncnt (rnm) from thc Standard Surgical Unit x (right) y (antcrior) z (superior) Magnitudc [trTt

b. Prc-opcrativc Surgical Unit vs Post.opcrativc Surgical Unit

Land¡narks Landnrark Diffcrcnccs (mm) x (right) y (antcrior) z (supcrior) Magnitudc inferolateral orbitale le[L -1.2 5.1 0.3 5.2 infero-lateral orbitale righ L 4.5 5.4 7.2 10.1 orbitale zygomatic lefi 11 -l.z 3.4 orbitale zygomauc right 32 2.0 ?o 4.8 pre-articuiare left -4.8 l 1.0 -0.5 2.1 pre-articulare right 2.1 204 -0.1 20.5 superior orbiLale lelt 0.3 5.6 2.8 6.3 superior orbitale righL -l.1 5.1 4.9 1.7 supero-lateral orbitale lc[L 1.3 6.3 -2.9 1.0 supero-lateral orbiLale righL 3.0 4.8 2.9 6.4 supero-medial orbitale lefi -02 l5 6.1 6.2 supero-medial orbitale righL z.l 2.5 1.3 8.2 zygo-frontale lefL -26 8.2 -1.4 8.7 zygo-fronrale righL 36 70 5.6 9.7 zygo-maxillare infcrius latcrale Le[L -6. I 1.3 t.1 6.5 zygo-nraxiìlare irrlcri us latcralc right l0l 1.8 2.2 10.5 zygo-temporalc lcft le 9.6 2.2 10.3 zygo-temporale right 3Iì 94 5.1 I 1.6

'l'ranslation of Prc.opcrativc Surgical Unit I)isplaccrncnt (mrn) to Post-opcrat¡ r'c po.sition x (right) y(antcrior) z(supcrior) Magnitude I | I l 0r

Appendtx 3P aqe lxvu Appendix 3 Results of Three Dimensional Quantitative Analysis

Morph

Patient LW Extended Fronto-orbital Advance (continued):

c. Post.opcrativc Surgical Unlt vs Standard Surgical Unit

Landmarks Landmark Diffcrenccs (mrn) x (right) y (antcrior) z (supcrior) Magnitude inferolateral orbitale left -4.9 -0.2 aa 5.4 infero-lateral orbitale right 9.4 3.4 10.2 orbitale zygomaúc left -6.9 -6.6 -l.9 9.7 orbirale zygomatic right 1 1.9 -1.1 0.8 t2.0 pre-arriculare left -6.2 1.9 - t.L 10.6 pre-aniculare right 5.0 15. I -2.4 l6.l superior orbitale left -5.6 9.4 -o.2 l 1.0 superior orbitale righL t3.s 6.7 3.1 157 supero-lateral orbitale left -6.9 4.1 26 8.7 supero-lateral orbitale righL ll.l 3.4 ?o 12.0 supero-medial orbitale left 1.8 6.2 2.1 6.8 supero-rnedial orbiLale righL 6.0 7.8 10.3 'L zygo-fronrale left 7.3 ?o -l 8 8. I zygo-fronralc right I 1.7 2.0 39 12.5 zygo-maxillare inferius larerale lefi -6.1 -3.1 1.5 zygo-maxillare inferius laterale right 9.9 -1.2 71 10.3 zygo-temporale left -5.6 3.1 6.4 9r zygo-temporale right 9.8 tì.6 13.6

'franslation of Post-opcrative Surgical Unit Displaccrncnt (rnrn) from the Standard Surgical Unit x (right) z(supcrior) Magnitudc I r(antcrior) | | 1.8 3.5 1.4 T TJ*-

Page lxviii Crouzon Syndrome Appendix 3 Results of rhree Dimensi

Patient HC Fronto-orbital Advance:

a. Pre-opcrativc Surgical Unit vs Standard Surgical Unit

Landmarks Landmark Diffcrcnccs (mm) x (right) y (antcrior) z (supcrior) Magnitude

superior orbi¡ale leIL -83 -l 8.8 18.9 )'7 0 s uperior orbirale righL 27 -11 8 22.4 25.4 supero-lateral orbiLale superius lcfi -?0 -11.9 19.9 supero-lateral orbirale superius righr -l I I 13.6 17.8 supero-medial orbirale lefi -6.8 -l 1.6 19.'t 23.8 supero-medial orbiralo ri ght -4.9 -9.8 17.1 20.8 alare left -04 -13.4 18.5 22.8 alare right -3 1 -16 0 150 22.2 anterior nasal spinc -12 1 17.2 21.5 ecLo-canine superiu s left -t2 -15 3 16.9 22.8 ecto-canine superius righL 1.4 -15 7 16.6 22.6 ecto-incision r< central superiris lcft -15 I 13.9 20.5 ecto-i¡cision central superius right -l.l -15 3 15.2 21.6 cctornolare lst supcrius Lcl't 2.6 .1 5 t0.2 12.9 ectomolâre 1st superius righr -ll -8 1 110 15.4 greater palatine foranlen lelt -l 6 -6 I 5.6 8.4 greater palatine ')f foranren right -6 I 4.6 8.1 inferolateral orbiralc lefr -0.6 -19 I t0.z 21.7 inferolateral orbita le righr -64 -t5 2 tt.2 20.0 laLeral orbitale lefr -2 I -17 0 8l 18.9 lareral orbitale 11 right -11 1 I 1.6 16.6 maxillary tuberosiL), lefi -2.4 -63 6.7 9.5 maxillary tuberosir), right 0.1 -3.4 6.8 1.6 medial orbitale lefr -3.1 -12.1 r 5.3 20.1 medial orbitale righr -3,0 -10 5 203 23.0 n a sale aa -7.4 15.9 17.8 nas10n -3.4 -12.1 t8.2 22.1 naso-lacrimal inferius lefL 2.1 -t4 4 18.8 23.9 naso-lacrimal inferius righL -56 -IJ.J t7 -3 22.5 orbitale left -4.5 -18 6 9.6 21.5 orbitale right -6.1 -15.4 12.8 21.0 posterior nasal spire -66 4.4 8.4 prosthion -1.8 -t3 9 12.8 18.9 subspinale -2.6 -16 0 10.6 t9.4 superior naso-maxillare lef t -1.4 -ll6 17.3 20.9 superior naso-rnaxillare righr -34 I 1.9 18.3 22.0 superoJateral orbirale left -39 -r1 9 19.9 supero-lateral orbiLalc righr -l 9 -l I .t 121 flz zygo-fronLale (1 lefi superius) -?o -l8 tì 6.2 20.2 zygo-frontale righL (+ 5¡pgr¡rr; -0.4 -13 9 18 15.9 zygo-maxiJlarc inferius lelr 62 -13 7 8.0 t] .o zygo-max ilJare inl crius righr ,to 2 -t? 3 I t.8 19.8 zygo-temporale lefr 2.2 -13 6 1.1 15.8 zygo-temporale righL -5.5 -10 0 I 1.6 16.2 canine superius lefr 1') -l I 5 t5.4 t9.3 canine supcrius righL -33 -99 16.0 19. I disto-molare supcrius left 2.6 -1.6 9.2 122 disto-molare superius right -6.3 -54 9.8 12.8 incision superius lefi -l 9 -t4 2 14.5 20.4 incision superius righr -1.4 -li 1 14.5 19.9 medio-molare lst superilrs lefi 1.8 -62 I 1.3 13.1 medio-molare lsr supcrius righL -7.8 .1 Z I1.8 15.9

'franslation of l)rc-opcrativc Surgical Unit I)isplaccnrcnt (rnrn) from thc Stanrlartl Surgical Unit x (right) y (antcrior) z (supcrior) Magnitudc mm

Appendix 3 Page lxix Appendix 3 Results of Three Dimensional Quantitative Analysis of Surgical Morphology (continued):

Patient HC Fronto-orbital Advance (continued):

b. Prc-operative Surgical Unit vs Post.opcrativc Surgical Unit

Landmarks Landmark Diffcrcnces (mm) x (right) y (antcrior) z (supcrior) Magnitudc

superior orbitale lef¡ -3 I 13.4 8.9 r6.4 superior orbitale right -63 9.9 4.5 t2.6 supero-lateral orbitale superius iefi -1.5 10.9 6.8 12.9

supero-Iateral orbitale superius right -0.5 2r.2 J. -1 2t.4 supero-medial orbitale left -3. I 11.0 3.6 12.0 supero-mediaÌ orbitale righr -4.6 I 1.4 4.8 13.2 alare left - -). -) 15.1 5.1 t].l alare right -3 1 11.4 65 18.9 anLerior nasal spine - t.-t 17.0 4.1 17.8 ecto-canine superius lefL -2.8 11.4 24 l?.8 ccto-cânûre superius righL 2.3 19.4 42 20. l ecto-ircision central superius [efL -3.0 l8 0 3.5 I 8.5 ecto-incision central superius right 2.1 t7.6 3.0 18.0 ectomolare lst superius left -l.l 15.1 2.3 t5.9 ectomolare lst superius righL -2.0 18.2 1.5 18.4 greater palarine loramen left -9.2 14.6 -5.0 11 .9 greater palatine foramen right 4.3 r4.9 15.9 inferolateral orbitale left -t.2 154 2.0 15.6 infero-lateral orbitale right -0.6 20.0 48 20.5

lateral orbitale left -3. 1 I 1.5 12.2 17.1 lateral orbitale right t6.7 I1.4 20.4 maxillary tuberosity left -1.4 15.7 4.1 16.2 maxillary tu berosity right o1 11 4 4.1 17.8 rnedial orbitale left - 1.9 18.1 10.8 21.2 medial orbitale right -5.9 19.5 5.6 21.1 nasale -5.8 154 5.9 r7.5 nâsron -45 15.5 4.1 16.6 naso-lacrimal inferius left -5.8 15.5 2.0 16;7 naso-lacrimal inferiu s righL -2.3 16.1 5.2 n'l orbitale left -3.8 I 1.8 4.6 13.2 orbitale right 2.5 11 4 3.0 r7.8 posterior nasal spine 0.9 15.5 5.3 16.4 prosthion 15.0 6.1 r6.4 11 subsprnale 16.'7 8.5 18.9 superior naso-lnaxilÌare lefl -4 1 16.3 6;l t8.2 superior naso-m axillare righ t -5 I 16l 6.3 18.0 supero-lateral orbirale left -l 5 10.9 6.8 t2.9 supero-lateral orbitale right t.2 21 1 43 22.1 zygo-frontalc lefL (+ s¡0"¡rr¡ -4.6 t32 56 l5. t zygo-frontale right (l superius) -08 20.4 4.3 20.9 zygo-maxillarc inferius left -l 8 12.5 5.t l3.l zygo-maxillare irferiu s right -36 t9.4 2.1 19.9 zygo-temporale lefL -2.1 l2.ti t.l 13. I zygo-remporale right -23 t9 8 3.t 20.3 canine superius left -22 13.6 l.t 13.9 canine superius right -t.4 t51 no 15.8 disto-molare superius left -1 5 13.9 t.z 14.0

disLo-molare superius right -3. 1 14.6 4.4 15.6

incision superius left -l.8 14. 1 0.4 14.3 incision superius right -3.1 14.9 3.5 15.8 mediornolare 1st superius left 0.0 12.6 -2.3 12.8 nledio-molare lst superius right -3 1 t].3 t.6 17.6

'I'ranslation of Prc-opcrativc Surgical Unit Displaccrncnt (rnrn) to Post-opcrativc position x (right) r(antcrior) z(supcrior) Mrgnitudc I.z3 lrs.qI Irc| |

Page lxx Crouzon Syndrome Appendix 3 Results of Three Dimensional Quantitative Analysis of Surgical Morphology (continued):

Patient HC Fronto-orbital Advance (continued):

c. Post-operativc Surgical Unit vs Standard Surgical Unit

Landmarks Landrnark Diffcrcnccs (mm) x (right) y (antcrior) z (supcrior) Magnitude

superior orbiøle left -t4.6 -3.9 27.2 31.1 superior orbitale righr -5.9 - 2.5 273 28.0 supero-lateral orbitale superius lefi -8.1 -6.4 r 3.8 t7.2 supero-lateral orbirale superius right -5.0 10.3 t't.6 21.0 supero-medial orbiraÌe left -11.9 0.5 22.8 25.7 supero-medial orbit ale righr -11.2 2.3 22.5 25.2 alare left -56 2t 23.9 24;7 alare right -95 1.7 21.6 23.6 anterior nasal spine -1 3 4.3 2t.t aa1 ecto-canine superius lcfL -5.8 t.8 19.0 19.9 ecto-calìine supcrius righL -59 4.0 2t0 22.2 ecto-incision central superius lcfl -6 1 21 n.1 18.4 ecLo-ircision ccnLral superitrs righL -55 2.O 18. I 19.0 ecLomolare lst superius lefr 1.0 7.2 t2.l 14.2 ectomolare lst superius right -9.6 10.5 t2.1 19.1 greater palaline foramen left -ll.l 8.2 0.6 13.8 greater palatine foramen right 1.3 8.6 t.1 8.9 ìnfero-lateral orbitale lefr -4.6 -37 I 1.6 13.0 infero-lateral orbiLale righL -9.2 5.5 16.5 19.6 lareral orbitale left -1.1 -5.1 19.6 21.7 lateral orbirale righL 5.1 23.6 25.1 maxillary tuberosit), Iefi -4.0 o? 10.5 r4.5 maxillary tuberosit), right 1.0 r 3.3 1 1.4 t7.5 medial orbitale left -1 0 5.8 25.8 n.4 medial orbitale righL - 10.7 9.4 25.9 29.6 n asale -9 1 8.2 21.6 25.1 n a s10n -9.9 39 22.2 24.6 naso-lacrimal inferius lefi -5.3 0.6 20.7 21.3 naso-IacrimaI infcrius nght -9.8 4.1 22.6 25.O orbitale left - 10.9 -6.3 13.7 18.6 orbitale right -<1 2.1 t6.z '1,7.4 posterior nasal spìre 8. tì 9.8 13.3 prosthion 0.9 18.7 t9.6 subspinale -6.6 0.7 19.0 20.1 superior naso-maxillare [c[t -8 I 4.9 239 25;l superior naso-maxillarc righr - 10.5 4.1 245 n.0 supero-Iateral orbitale lefL -8 I -6.4 13.8 17.2 su¡rero-latcraÌ orbitale righr -5.0 t 0.3 n.6 2r.0 zygo-frontale left (+ supcrius) -l r 3 -49 tr2 t6.6 zygo-frontale right (+ superi¡s) -3.4 6.4 t2.9 14.8 zygo-maxiìlare inferius lefL 28 tt2 1l .9 zygo-maxillare hferius rìgh L -15 I 8.2 15.0 22.8 zygo-temporale left -t2 8.2 8.7 zygo-remporale nght -9.1 10.3 16.0 21.1 canine superius lefL -54 1.9 16. I t7.t canine superius righL -5.4 5.6 15 1 17.0 disto-molare superius lefr 0.7 5.2 10. I I1.4 disto-molare superius right -9.4 9.4 14.5 19.6 incision superius lefr -5.1 -0.3 147 15.6 incision superius righr -64 0.9 17.9 19.0 nredio-molare lst superius lclr l6 5.5 8;l 10.4 medio-molare 1st superius right -11.2 10.5 136 20.5

î'ranslation of Post-opcrativc Surgical Unit Displaccnrcnt (mm) from thc Standard Surgical Unit x (right) y (antcrior) z (supcrior) Magnitudc mm

Appendix 3 Page lxxi