Ophthalmic Features and Visual Prognosis in the Treacher-Collins

642 BritishJournalofOphthalmology 1993; 77: 642-645 Ophthalmic features and visual prognosis in the

Treacher-Collins syndrome Br J Ophthalmol: first published as 10.1136/bjo.77.10.642 on 1 October 1993. Downloaded from

Richard W Hertle, Sule Ziylan, James A Katowitz

Abstract The ocular findings and visual prognosis were reviewed in 24 patients with the Treacher- Collins syndrome who were evaluated in the craniofacial clinic in the Division of Pediatric Ophthalmology at Children's Hospital of Philadelphia between 1980 and 1991. AU patients had some abnormality. Vision loss was present in 37% ofpatients. Amblyopia was present in 33%, significant refractive errors were present in 58%, and anisometropia was documented in 17%. Strabismus was present in 37% and significant lid and adnexal abnormalities were seen in 96%. The prognosis for normal vision in at least one eye is good but vision loss secondary to amblyopia is more resistant to treatment owing to other medical problems and social concerns. (BrJ Ophthalmol 1993; 77: 642-645)

Figure I This patient has a severeform ofTreacher-Collins The Treacher-Collins syndrome (TCS) is an syndrome. autosomal dominant facial malformation with variable penetrance and is also known as zygo- auromandibular dysplasia or mandibulofacial choanal atresia, and lingual obstruction because dysostosis (MFD).'4 This bilateral anomaly of mandibular retrusion.>" Cleft lip and palate, represents a cluster ofmalformations resulting in enlarged sphenoid bone fissures, and skeletal zygomatic, temporoaural, and mandibular and cranial synostoses are other reported abnor-

dysplasia. It was first reported by Berry in 18895 malities. 12-13 This report summarises our http://bjo.bmj.com/ in a mother and daughter. Rogers,3 and experience managing 24 patients as part of the Franceschetti and Klein' further clarified the craniofacial clinic in the division of ophthal- clinical findings in their case reports. Most mology at the Children's Hospital of patients with TCS are ofnormal intelligence, but Philadelphia. maybesociallyaffected owing to theirappearance or appear retarded secondary to hearing loss. TCS is characterised by hypoplasia and Methods on September 28, 2021 by guest. Protected copyright. retrusion of the malar region, obliteration of the The craniofacial clinic is a monthly multi- frontonasal angle, and a receding chin. Pro- specialty clinic at the Children's Hospital of trusion of the nose and maxilla may produce an Philadelphia. Patients have an ophthalmic enophthalmic appearance. The inferior lateral examination as part of a day long process which angle of the orbit is defective and the supero- includes evaluation by many paediatric sub- lateral part of the orbit is displaced caudally specialties including: plastic and reconstructive giving the orbit an egg shaped appearance. The surgery, neurosurgery, oral and maxillofacial orbital contents appear displaced into the surgery, dentistry, genetics, ophthalmology, deficiency created by the malar hypoplasia'l otolaryngology, psychiatry/psychology, social (Fig 1). work, and speech and hearing. This group meets The Children's Hospital Ocular abnormalities include pseudo- at the end of the clinic day to discuss patient ofPhiladelphia and The colobomas (hypoplastic subcutaneous tissue, evaluations and proposed treatments. Scheie Eye Institute, The and and true University of muscle) colobomas (full thickness The clinical records of 329 patients seen for a Pennsylvania, absence of tissue) of the lids, especially infero- complete ocular examination from 1980 to 1991 Philadelphia, USA laterally, canthal dystopia, orbital lipodermoids, have been entered into a computerised database R W Hertle limbal dermoids, and occasional microphthalmos in the Division of Pediatric Ophthalmology. S Ziylan I J A Katowitz and anophthalmos. Cataracts, lacrimal duct Data include name, ages at first and most recent Correspondence to: atresia, pupillary ectopia, dystichiasis, and uveal examinations, craniofacial diagnosis, best and Richard W Hertle, MD, colobomas have all been reported.5"9 Strabismus worst visual acuities, amblyopia, pupillary Division of Ophthalmology, The Children's Hospital of has been reported in several forms including abnormalities, motility disturbances, results of Philadelphia, 34th St and Civic esotropia, exotropia, Duane's syndrome, and fusion testing, intraocular, disc or retinal Center Blvd, Philadelphia, PA 19104, USA. cranial nerve palsies."9 abnormalities, lid and adnexal abnormalities, Accepted for publication A large variety of ear abnormalities can be cycloplegic refraction (40 minutes after 1% 28 April 1993 present. Respiration can be affected by sinus and cyclopentolate (Cyclogyl) in children older than 1 Ophthalmicfeatures and visualprognosis in the Treacher-Collins syndrome 643

Table I Clinical characteristcs of24 patients with Treacher-Collins syndrome PT VA Refraction Strabismu HX amblyopia Lid/adnexal abnormality Br J Ophthalmol: first published as 10.1136/bjo.77.10.642 on 1 October 1993. Downloaded from 1 20/30 OD + 125 Ortho No Dacryostenosis OU, pseudocoloboma OU 20/20 OS +[175 2 20/20 OD -1-00 +0 75 x90 Ortho No Ptosis, pseudocoloboma, telecanthus, epicanthus OU 20/20 OS -0 50 +0 50x90 3 20/20 OD +2 50 Ortho No Canthal dystopia OU, telecanthus, epicanthus OU 20/20 OS +4 50 4 F&F OD Plano XT No Lower lid coloboma OU F&F OS +0.50 5 20/20 OD -1-00 +0 75 x 12 OALSO OS Ptosis OU 20/60 OS -0 50 +1 00x 160 6 20/20 OD +0 75 Ortho No Lower lid coloboma OU 20/20 OS +0-25 7 20/30 OD +0 50 Ortho No Dacryostenosis OU, pseudocoloboma OU 20/30 0S -0 50 +1 00x60 8 20/20 OD + 150 XT No Canthal dystopia OU, lower lid coloboma OU 20/25 OS +1-50 9 20/20 OD -4 50 + 150x 180 CN VI palsy, OD Pseudocoloboma OU, canthal dystopia OU 20/20 OS -3 50 +2 75x75 LHT 10 F&F OD +0 50 Ortho No Dacryostenosis OU, canthal dystopia OU, absent inferior F&F OS +0 50 systems 11 20/200D +1-00 +0 25x31 ET OS CanthaldystopiaOU 20/40 OS +1-75 +0 50x45 12 20/20 OD +1-00 Ortho No Canthal dystropia OU, pseudocoloboma RLL, 20/20 OS +[-00 + 1 00x90 coloboma RLL 13 20/20 OD +1-25 Ortho No Pseudocoloboma OU, canthal dystopia OU 20/20 OS +1-25 14 20/25 OD -0-75 + 1 00x 135 Ortho OD Pseudocoloboma OU 20/25 OS -0 50 +0 50x45 15 CSM -1-00+1 00x175 XT,RHT No None CSM -2-00 +1 00x45 16 20/20 OD +2 75 +3O00x 150 Ortho No Pseudocoloboma OU 20/20 OS +2-00 +3 25x 14 17 CSMOD -1-25 +1[75x 140 Ortho No PseudocolobomaOU CSM OS -3 00 +2 25x40 18 20/20 OD +0 75 Ortho No Coloboma OU, entropion OU, trichiasis OU 20/20 OS +0-25 19 CF OD +4-00 + 1 00x45 XT OD Ptosis OU, lower lid coloboma OU 20/20 OS +1-25 20 20/200 OD +0 50 Ortho No Canthal dystopia OU, (CVI) pseudocoloboma OU 20/200 OS +0 75 21 20/30 OD -100 +075x 135 V-XT, No Pseudocoloboma OU 20/40 OS -1-00 +0 75x60 OAIOOU 22 20/40 OD -2-00 +3 00x 135 Ortho OD Ptosis OU, canthal dystopia OU 20/25 OS -[175 23 20/30 OD +2-00 Ortho No Canthal dystopia 20/40 OS +2-00 24 20/30 OD +[125 +3 00x 165 ET OS Canthal dystopia pseudocoloboma OU 20/50 0S +0 75 +5 00x20 VA=visual acuity; OD=right eye; OS'=left eye; OU=both eyes; CSM=central, steady, and maintained gaze; Ortho=orthophoria; XT=exotropia; OALSO=overactionofleftsuperioroblique; CN VI=cranial nerveVI; LHT=lefthypertropia; RHT=righthypertroPia; ET=esotropia; F&F=fixes and follows; CVI=central visual impairment; V-XT='V' pattern exotropia; OAIOO=overaction of the inferior oblique http://bjo.bmj.com/

year of age and 0-5% under 1 year of age), and hyperopia greater than +2 00 sphere, myopia type ofstrabismus procedures and results. greaterthan-0- 75 sphere,or astigmatismgreater Fifty one per cent of these patients had than 0 75 dioptres at any examination. Aniso- craniofacial stenoses, 25% had clefting syn- metropia was defined as greater than 1 50 dromes, 17% had other varied and often singular dioptres difference between the eyes in any on September 28, 2021 by guest. Protected copyright. craniofacial deformities, 7% had orbital tumbours meridian at any examination. or trauma and were evaluated by the entire team. The data included in this report are from all patients who were examined in the craniofacial Results clinic between 1980 and 1991 with the diagnosis Twenty four of 329 (7%) patients or 17% of TCS. Patients who had other first and second of patients excluding craniofacial stenoses, branchial arch syndromes (for example, tumours, and trauma were diagnosed with TCS. Goldenhar's, facial microsomia) or clefting Patient age at first examination ranged from 2 5 syndromes (for example, Stickler's syndrome, months to 20 years (median 2-7 years). Fourteen typical orofacial ocular clefts) were excluded patients were male. from analysis. All data used for this analysis were All patients examined in this study had some accumulated from one or multiple examinations ocular and adnexal abnormality (Table 1). of each patient. Twenty patients were examined Refractive errors were present in 14 (58%) on more than one occasion and four were patients. Five patients had anisometropia, 13 examined once. If an ocular abnormality was had mixed astigmatism, and one had simple present at any examination the date of onset and myopia. follow up treatments and results were recorded. Ten eyes (21%) in nine (37%) patients had or The follow up on the 20 patients with repeat have abnormal vision. Eighteyes in eight patients examinations ranged from 1 to 12 years with an (33%) had amblyopia at some time during their average of 4-5 years. All abnormalities reported evaluation and follow up as part of the cranio- were diagnosed during either their initial or facial clinic. One patient having 20/200 visual subsequent evaluations in the Division of acuity bilaterally by Teller acuity card testing Pediatric Ophthalmology. had central visual impairment (post-chiasmal Ametropic refractive errors were defined as dysfunction of unknown aetiology) and was also 644 Hertle, Ziylan, Katowitz

mentally retarded (patient 20). Thevisual acuities unknown. Recent evidence suggests that the listed in the table are those at the last examina- genetic defect responsible for TCS maps to the

tion. All patients with amblyopia have had or are long arm of chromosome 5.9 Postulated con- Br J Ophthalmol: first published as 10.1136/bjo.77.10.642 on 1 October 1993. Downloaded from currently receiving treatment. This consisted of sequences of this genetic defect may cause a refractive correction when indicated combined complete absence of embryonic malar bone with occlusion therapy. At the time ofthis report centres or their outgrowth, or hypoplasia of total treatment periods ranged from 3 months to bones or parts of bones after development.'92' 4 years, with a median of 21 months. Six of the There is experimental and embryological eight patients did not have equal visual acuities at evidence which suggests that abnormal neural their most recent examination. All these patients crest migration as early as 4 months' gestation had poor compliance with the instructed may be related to the defects of TCS.2>22 The occlusion regimen. genetic defect in TCS may be responsible for Strabismus was diagnosed in nine (37%) creating this deformity by disrupting migration patients. There were two patients with esotropia, of these neural crest cells.20 It is believed that five with exotropia, one with a cranial nerve six these defects occur before the 17 mm crown to palsy, and one with overaction ofthe left superior rump length (17-20 weeks).' 2' In other work oblique muscle. One patient had a V pattern and with animal embryos abnormal stapedial artery associated inferior oblique muscle overaction in blood supply during the sixth week of embryo- addition to the exotropia (Table 1). genesis can produce ear and facial abnormalities Except for one patient with bilateral pseudo- similar to TCS.20 In this model the associated papilloedema secondary to buried drusen, no overlying soft tissue and muscular defects are intraocular abnormalities were observed. the results of underlying aberrant bony Lid and adnexal eye disorders were present in maldevelopment. 24 patients (100%) (Table 1). Canthal dystopia Abnormal lid and adnexal morphology and was present in 24 patients, dacryostenosis in function, ocular motility problems, refractive three patients, blepharoptosis in six patients, errors, and amblyopia are the abnormalities lateral lower lid true coloboma in six patients, which most frequently require treatment. and pseudocolobomas in 13 patients. Entropion Specific treatment of associated ophthalmic and trichiasis were each present in one patient. abnormalities in patients with craniofacial anomalies follow similar principles utilised in patients without the anomalies. Discussion Lid malpositions, colobomas, and pseudo- The TCS belongs to a group of craniofacial colobomas are usually treated surgically. anomalies having in common maldevelopment of Inadequate underlying bone in the lateral canthal the first and second branchial arches.' 116 area presents a unique challenge. Lateral canthal Characteristic clinical, familial, and chromo- dystopia can be repaired at the time of maxillary somal findings justify separation ofthis syndrome reconstruction but the maxillary hypoplasia may from other abnormalities in development of the need several staged procedures. It is sometimes first and second branchial arches. The others advantageous to postpone definitive lateral http://bjo.bmj.com/ include facial clefting syndromes, Goldenhar's canthal reconstruction until these procedures syndrome, facial microsomias, Miller's have been completed. syndrome (digit and limb abnormalities, and Motility problems are treated after amblyopia acrofacial dysostosis), and Nager's syndrome therapy and correction of refractive errors. (radial limb deficiencies).'5 16 Surgical treatment of strabismus proceeds Franceschetti and Klein' suggested a according to the strabismus diagnosis and not on September 28, 2021 by guest. Protected copyright. classification system consisting of five clinical necessarily delayed until other craniofacial forms: (1) the complete form, having all known surgery is performed. We prefer to use the fornix features, (2) the incomplete form, presenting incision in approaching the muscle because is it variably with less severe ear, eye, zygoma, and easier to examine all the muscle insertions. mandibular abnormalities, (3) the abortive form, Anomalous insertions are seen with increased in which only the lower lid pseudocoloboma and frequency in patients with other craniofacial zygoma hypoplasia are present, (4) the unilateral malformations and in some instances may form, with the anomalies limited to one side of contribute to the type of strabismus.23 the face regardless of severity, and (5) the Discovering anomalous muscle position or atypical form or incomplete form combined with number during surgery may influence the other abnormalities not usually part ofthe typical surgical plan. syndrome. The percentage of patients with vision loss They reported that the most common forms (37%) and strabismus (37%) in this series is were the typical and atypical (1 and 5) higher than in the general paediatric population. varieties.'2412 The existence of the unilateral Other series do not report the vision in their form has been challenged and' may actually patients making comparison between series represent a type of facial microsomia which is difficult.357 The overall visual prognosis in these often unilateral and shares many common patients is favourable although there is a much features with TCS.7 18 This classification system higher incidence of unilateral vision loss. The represents a spectrum ofvariability in the clinical most common reason for this is amblyopia. As in presentation ofthis malformation. This system is patients with other craniofacial syndromes this presented for historical purposes as the func- is due to a combination of factors which tional and cosmetic consequences and treatment are independently amblyogenic.2425 Refractive options do not depend on one or another form. errors, anisometropia, strabismus, and ptosis The aetiology of the facial defects in TCS are combined to various degrees were responsible Ophthalmicfeatures and visualprognosis in the Treacher-Collins syndrome 645

in our patients. No patients 2 McKenzie J, Craig J. Mandibulofacial dysostosis (Treacher- for the amblyopia Collins syndrome). Arch Dis Child 1955; 30: 391-411. had structural problems of the globe which 3 Rogers BO. Berry-Treacher-Collin's syndrome: a review of

contributed to their vision loss. Patient 20 had 200 cases. BrJPlastSurg 1964; 17: 109-13. Br J Ophthalmol: first published as 10.1136/bjo.77.10.642 on 1 October 1993. Downloaded from 4 Treacher Collins E. Case with symmetrical congenital notches post-chiasmal visual dysfunction (central visual in the outer part ofeach lower lid and defective development impairment) which, by history, was the result of of the malar bone. Trans Ophthalmol Soc UK 1900; 20: 190. 5 Berry GA. Note on a congenital defect (?coloboma) of the a perinatal anoxic insult. Of the eight patients lower lid. Roy Soc London. Ophthalmol Hosp Rep 1889; 12: with amblyopia, equal vision was only obtainable 255. in two at the last examination. This emphasises 6 Wang MF, Millman AL, Sidoti PA, Goldberg RB. Ocular findings in Treacher Collins syndrome. Am J7 Ophthalmol compliance difficulties in these patients. Oral 1990; 110:280-6. and auricular function may also be affected and 7 Hurwitz P. Mandibulofacial dysostosis. 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