BritishJournal ofOphthalmoloV, 1991,75,591-597 591 Heterogeneity in dominant anterior segment malformations Br J Ophthalmol: first published as 10.1136/bjo.75.10.591 on 1 October 1991. Downloaded from

Gerd E Holmstrom, William P Reardon, Michael Baraitser, John S Elston, David S Taylor

Abstract lost, and similarities to scleral tissues with Peters' anomaly is usually a sporadic or auto- irregularly arranged collagen fibrils of variable somal recessive condition. We present three dimensions are seen instead.'0'2 '4 Elastic fibres families whose members had dominantly have been described in the anterior stroma.'213 inherited anterior segment anomalies with The corneal endothelium and the Descemet's variable expression, including typical Peters' membrane are attenuated, incomplete, or anomaly in at least one family member. Slit- absent.'012-14 lamp examination of parents and family A prominent Scwalbe's line, sometimes called members of children with Peters' anomaly is posterior embryotoxon, has been reported in therefore important to exclude dominant 8-32% of otherwise normal eyes.4 116 However, inheritance. Axenfeld" used the term 'embryotoxon corneae posterius' when he described a patient with a whitish, prominent line in the posterior A variety of anomalies may be seen as a result of periphery of the , close to the limbus, and disturbances of the development of the anterior with strands up to this line. Subsequently a segment of the eye, including Peters' anomaly, prominent Schwalbe line in combination with Rieger's anomaly, Axenfeld's anomaly, and iris strands to the line has been called Axenfeld's sclerocornea. Many individual cases fit into the anomaly. It is associated with glaucoma in 50%,'1 more clearly defined patterns or syndromes but this condition being known as Axenfeld's syn- they often overlap, defying specific description. drome. Peters' anomaly consists of a central corneal In 1935 Rieger described cases with iris leucoma, a central defect of Descemet's mem- changes including hypoplasia, corectopia, and brane, and synechiae between the iris and the hole formation, in addition to findings consistent cornea.' The affected cornea is rarely vascular- with Axenfeld's anomaly.'9 Subsequently this ised, and the peripheral cornea is clear, though combination has been known as Rieger's scleralisatipn of the limbus is common.2 Kerato- anomaly. In 1969 Alkemade4 reviewed the litera- lenticular adherence with shallowing of the ture together with a study of patients with anterior chamber may be seen.2 80% ofthe cases 'dysgenesis mesodermalis of the iris and the are bilateral and glaucoma may occur in 50% of cornea'. A detailed description of Rieger's http://bjo.bmj.com/ the cases.4 Other associated findings include anomaly was given, the main constituents being congenital cataract, which may be related to the hypoplasia ofthe iris stroma and abnormalities of , microphthalmos, , the iridocorneal angle - that is, a prominent cornea plana, sclerocornea, and dysgenesis ofthe Schwalbe's line with iris strands extending over angle and the iris.3'5 Congenital perforation of the angle to the Schwalbe ring. Glaucoma occurs the cornea has also been reported.67 Associated in 60% of cases,4 and an ill defined iridocorneal systemic findings affecting the central nervous junction is commonly seen.4 The cornea is often on September 29, 2021 by guest. Protected copyright. system, cardiovascular system, urogenital normal, but microcornea or macrocornea may be system, digestive system, skull and face, and seen.4 Peripheral opacities of the cornea at the limbs are reported.4 Histologically the posterior site ofthe irideocorneal adhesions are described,4 cornea shows the most significant changes. The as are central leucomas.4202' Cornea guttata has Hospitals for Sick periphery is normal, but the central part shows also been mentioned.22 Pupil abnormalities are Children, Great Ormond an absence or marked attenuation of the endo- frequent (72%); abnormalities in and Street, London WC1 shape, size, Department of thelium and Descemet's membrane.23 Changes location are seen as well as polycoria.4 Ophthalmology in the angle, in the form of numerous iris uveae is described22 and so are coloboma of the G E Holmstrom processes adherent to the trabecular meshwork, iriS22 23 and abnormalities. Epicapsular stars D S Taylor have also been mentioned.8 on the anterior lens surface,42224 ,422 Department of Clinical Sclerocornea was first described as an isolated subluxation,4202 cataracts of many types,42022 Genetics congenital anomaly in 1933.9 It often occurs and posterior lens opacities associated with W P Reardon M Baraitser together with cornea plana or other ocular anterior persistent hyperplastic primary anomalies, including microphthalmos, anoma- vitreous.26 Rarely other ocular anomalies may be Department of Neuro- lies of the anterior chamber, glaucoma, and associated: disc anomalies, chorioretinal ophthalmology, National 11 Hospitals for Nervous coloboma.2 10 In 90% of the cases sclerocornea colobomas, macular degeneration, choroidal Diseases, London is bilateral.2 It may affect either the peripheral or hypoplasia, and retinal detachment.4 J S Elston the entire cornea,'2 which assumes an opaque Some patients with Rieger's anomaly have Correspondence to: appearance approaching that of the . associated non-ocular developmental defects, David S Taylor, FRCS, Department of Macroscopically the opacity usually extends particularly of the teeth and facial bones.2728 The Ophthalmology, Hospitals for through the full thickness of the cornea." The combination of Rieger's anomaly and dental Sick Children, Great Ormond Street, London WC1N 3JH. cornea is vascularised superficially, but the anomalies is called Rieger's syndrome. Many Accepted for publication process may extend deeply. 12 Histopathologically authors fail to distinguish between Rieger's 28 February 1991 the lamellar organisation of the corneal stroma is anomaly and Rieger's syndrome. Even the 592 Holmstrom, Reardon, Baraitser, Elston, Taylor

original description by Rieger'9 included at least Kivlin et al,38 who report on several patients with

one case which can be identified as Rieger's Peters' anomaly in one eye and Axenfeld's Br J Ophthalmol: first published as 10.1136/bjo.75.10.591 on 1 October 1991. Downloaded from syndrome by having teeth abnormalities. How- anomaly in the other eye, that the various ever, the term 'Axenfeld-Rieger syndrome' has components might represent variable expression been proposed, since dental defects also have of mesodermal dysgenesis. However, these been noted among patients with findings con- authors do not describe the inheritance of these sistent with Axenfeld's anomaly.29 patients. A variable expressivity of a dominant Furthermore, it has been suggested that gene in anterior segment anomalies is reported Axenfeld's and Rieger's syndromes may be dif- by Hittner et al,39 Salmon et al,4' and Green and ferent expressions of the same gene.303' The Johnson.4' In the study of Hittner et al3' all dental defects include microdontia, hypodontia, family members had cataracts and corneal and oligodontia or anodontia.173' Facial abnor- opacities, but with large phenotypic variation. In malities are a frequent finding, and Rieger the study of Salmon et a"40 most affected mem- described maxillary hypoplasia with flattening of bers had microcornea with cataract but one had a the midface and a short philtrum.'9 A broad, flat typical Peters' anomaly. In Green and Johnson's nasal root, hypertelorism, and telecanthus have study" one patient had Peters' anomaly, also been described.4 Many other systemic abnor- others had peripheral scleralisation ofthe cornea, malities have been reported43': hand and feet while most patients had microcornea and malformations,433' cardiovascular anomalies,435 cataract. deafness,434 mental deficiency,4 myopathy," We report on three families which support the skin changes,437 umbilical hernias, and hypo- contention that Peters' anomaly, Rieger's spadias.2434 anomaly, sclerocornea, and Rieger's syndrome The genetics of this group of conditions as a might occasionally be the result of variable whole is problematic. It has been suggested by expression ofthe same genetic disorder. Case reports

Family I I& Figure I Pedigree data offamily 1. I and II refer to the I mw different generations in the pedigree. 1, 2, 3, etc refer to the 2 individuals within a particular generation. * =affected male. OI=unaffected male. O=affectedfemale. O=unaffected female.

ITrIL I 6~~~~~ '! 3 I2 http://bjo.bmj.com/ on September 29, 2021 by guest. Protected copyright. _~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.. ".....

Figure 2 Case 12. The right eye of the mother has a Figure 3 Case I 2. The left eye has a microcornea, superior microcornea, superior and inferior scleralisation, and a scleralisation, and . The vision is 6/36 with glasses cataract. The visual acuity is countinghfingers. (+130). II2

3.~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.....

~~~~~~~~~1

Figure 4 Case II 2. The right eye ofthis 5-year-old boy has microphthalmos, slight superior and inferior scleralisation, Figure S Case II 2. The left eye has microphthalmos, and peripheral iridocorneal adhesions. There is a horizontal sclerocornea, and peripheral iridocorneal adhesions and can nystagmus, and the best visual acuity is 6/36. only localise light. Heterogeneity in dominant anteriorsegment malformations 593

III 3 Br J Ophthalmol: first published as 10.1136/bjo.75.10.591 on 1 October 1991. Downloaded from

1113m~~~~~~~~~~~~~~~~fia..%

Figure 6 Case III 3. The right eye ofthis baby has Peters' Figure 7 Case III3. The left eye hassPeters' anomaly with a anomaly with a central corneal opacity and lens adhesions to more pronounced corneal opacity and ilens adhesions to the the corneal endothelium seen with gonioscope at 3 months of cornea seen at gonoscopy. The arrows iindicate the border ofthe age. The arrows indicate the border ofthe lens. lens.

Family 2 I Figure 8 Pedigree data offamily 2.

1 ~~~2 3

12 L http://bjo.bmj.com/ I2 _* on September 29, 2021 by guest. Protected copyright.

Figure 9 Case I 2. The right eye has iris hypoplasia, Figure 10 Case I 2. The left eye also has iris hypoplasia, posterior embryotoxon, peripheral iridocorneal adhesions, and posterior embryotoxon, peripheral iridocorneal adhesions, and a visual acuity of6/9. a visual acuity of6/12 (-2-5 dioptres).

Figure 12 Case I 2. The mother has short clinical crowns of Figure 11 Case I 2. Enlarged, irregular corneal endothelial the twofrontal teeth, which have been capped, aplasia ofthe cells withfocal defects. lateral incisors, and a right side cross-bite. 594 Holmstrom, Reardon, Baraitser, Elston, Taylor Br J Ophthalmol: first published as 10.1136/bjo.75.10.591 on 1 October 1991. Downloaded from

Figure 14 Case 11 The left eye has Peters' anomaly with a - central corneal opacity and afew peripheral iridocorneal adhesions The vision is countingfinger

Figure 13 Case II 1. The right eye ofthis 14-year-old boy has iris hypoplasia, partialposterior embyotoxon, afew peripheral iridocorneal adhesions. and a vision of6/9.

*;...:.. t ~~~ ~ ~~ ~ ~~ ~~~ ~~~ ~~~ ~~~ ~~~ ~~~ ~~~ ~~~ ~~~ ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.....

- Figure 15 Case II 1. This boy has maxillatry hypoplasia, evident by the malocclusion ofthe teeth. He has also two tw in the lower .. ~~~~~~fronwotal,capped teeth, hypoplastic premnolars jaw, and a tiny lateral incisor in the upperjaw. http://bjo.bmj.com/

II3~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ on September 29, 2021 by guest. Protected copyright.

Figure 16 Case II3 A 7-year old boy with a right eye with Figure 17 Case 113. The left eye has iris hypoplasia, iris hypoplasia, posterior embryotoxon, polycoria, cataract, posterior embryotoxon, peripheral iridocorneal adhesions and band keratopathy, glaucoma,and no perception oflight. a vision of6/9.

Figure 18 Case II 3. This boy has a bilateral cross-bite, which could be related to a maxillary hypoplasia. His dention _--~M is primary, and nothing canyet be said ofhis permanent teeth. Heterogeneity in dominant anteriorsegment malformations 595

Family 3 Br J Ophthalmol: first published as 10.1136/bjo.75.10.591 on 1 October 1991. Downloaded from I -M [17 2 3 L27~

3 4 5 Figure 19 Pedigree data offamily 3.

Case I 2. The mother has bilateral iris hypoplasia and partial posterior embryotoxon and normal vision.

Case II 2. A nine-year-old girl has bilateral iris hypoplasia andposterior embryotoxon laterally and a normal vision.

Figure 21 Case II 3. The left eye shows Peters' anomaly with a central corneal opacity, lens opacity, posterior Figure 20 Case II 3. This 7-year-old boy has a right eye embryotoxon, and glaucoma. There is no perception oflight. with iris hypoplasia, posterior embryotoxon (arrow), and a II3 normal visual acuity. http://bjo.bmj.com/ Case II 4. A two-year-old Discussion boy who has patchy iris are dis- as hypoplasia bilaterally. His Anterior segment anomalies caused by drome' to 'include all possible factors such vision appears normal. turbances in the early development of the eye. improper differentiation, absorption, or even The optic primordium develops from three shifting or mobilisation of tissue in its develop- different embryonic layers: neural ectoderm, mental stage'. Waring et al'8 presented an surface ectoderm, and mesoderm (primary anatomical description of the anomalies of the mesenchyme).4' Neural crest cells, a sub- anterior segment, based on the 'anterior on September 29, 2021 by guest. Protected copyright. population of cells emigrating from the dorsal chamber cleavage' theory, which they called 'a margin of the neural folds at about the time of stepladder classification'. However, Kupfer and neural tube closure, migrate into the primary Kaiser-Kupfer& did not find any embryological mesenchyme to form secondary mesenchyme.43 basis for this explanation of the anterior cleavage Subsequently three successive waves of second- syndrome and instead suggested a disturbance of ary mesenchyme migrate centrally from the rim the migration of the three mesenchymal waves ofthe optic cup to form the corneal endothelium from the optic cup, and the term 'mesenchymal and the trabecular meshwork, the keratocytes, dysgenesis' was proposed by Kenyon.2 Bahn et al and the anterior iris respectively." Johnston et suggested a classification of corneal disorders a1 43 showed that neural crest cells are the major based on neural crest origin, where sclerocornea contributor to the development of the corneal and Axenfeld's, Rieger's, and Peters' anomaly stroma, the corneal epithelium, the anterior were thought to be caused by abnormal neural chamber, the iris stroma, and the sclera in chick crest cell migration." Neural crest cell disturb- embryos, and light and electron microscopy ances also affect other parts of the body, which studies on the human corneal endothelium also explains the systemic symptoms sometimes point to a neural crest origin.45 associated with anomalies of the anterior seg- Several theories of the pathogenesis of the ment of the eye.8 different anomalies of the anterior segment have In the families described here the common been presented. Alkemade4 used the term feature in all three pedigrees is Peters' anomaly 'mesodermal dysgenesis ofthe iris and cornea' to in at least one family member. Other affected describe the pathogenetic mechanism. Reese and family members showed Rieger's anomaly, Ellsworth' believed that anterior segment sclerocornea, and other manifestations of anomalies were due to faulty cleavage and intro- anterior segment malformation. Although des- duced the term 'anterior chamber cleavage syn- cribed in association with a wide variety of 596 Holmstrom, Reardon, Baraitser, Elston, Taylor

extraocular abnormalities,38 Peters' anomaly is grees demonstrate that Peters', Rieger's, or thought to occur most often as an isolated, non- Axenfeld's anomaly may be seen as part of a genetic condition.2 However, there are some dominantly inherited condition without extra- Br J Ophthalmol: first published as 10.1136/bjo.75.10.591 on 1 October 1991. Downloaded from cases which are indisputably familial, and these ocular abnormalities. At present in the absence are mainly composed of multiple affected sibl- of extraocular abnormalities there is no way of ings suggestive of autosomal recessive inherit- knowing whether isolated Rieger's, Peters', or ance.44748 However, dominant inheritance has Axenfeld's anomalies confined to the eye are part also been shown,4950 and, although single cases of of Rieger's syndrome, and therefore likely to be Peters' anomaly have been associated with dif- transmitted to offspring, or not. This genetic ferent chromosome defects including chromo- counselling dilemma awaits the outcome of link- some 4 abnormality,5' ring 21 chromosomal age studies and the development of gene specific abnormality,"' and interstitial deletion of the probes for Rieger's syndrome. long arm of chromosome 1 12 a chromosomal basis is very unlikely to account for most cases. We thank Mr J Dart for endothelial studies offamily 2. We are also grateful to the Photographic Department for their help and for Axenfeld's anomaly has been reported to be support from 'Help a child to see'. inherited as an autosomal dominant condition.3' However, Brear and Insler did not find any 1 Peters A. Ueber angeborene Defektbildung der Descemet- schen Membran. Klin Monatsbl Augenhezlkd 1906; 44: 27- inheritable basis of Axenfeld's anomaly at all."3 40, 105-19. Sclerocornea is most often thought to be a 2 Kenyon K. Mesenchymal dysgenesis in Peters' anomaly, sclerocornea and congenital endothelial dystrophy. Exp Eye sporadic or dominantly inherited condition.' '2 Res 1975; 21: 125-42. A recessive inheritance pattern has, however, 3 Townsend W. Font R, Zimmerman L. Congenital corneal leukomas. 2. Histopathological findings in 19 eyes with also been mentioned." central defect in Descemet's membrane. Am J Ophthalmol Most published evidence points to Rieger's 1974; 77: 192-206. 4 Alkemade P. Dysgenesis mesodermalis of the in's and the cornea. syndrome being inherited as an autosomal domi- Assen: Van Gorcum, 1969. nant condition with a substantial variation in 5 Townsend W. Congenital corneal leukomas. 1. Central defect in Descemet's membrane. AmJ Ophthalmol 1974; 77: 80-6. expressivity.4 9243 345455 However, Forsius56 6 Krause U, Koivisto M, Rantakallio P. A case of Peters' found indications of recessive transmission. syndrome with sponataneous corneal perforation. J Pediatr Ophthalmol Strabismus 1969; 6: 145-9. Rieger's syndrome has been described in associa- 7 Heckenlively J, Kielar R. Congenital perforated cornea in tion with chromosomal abnormalities, including Peters' anomaly. AmJ7 Ophthalmol 1979; 88: 63-5. 8 Kupfer C, Kaiser-Kupfer M. New hypothesis of develop- chromosome 13 deletion,57 pericentric inversion mental anomalies of the anterior chamber associated with ofchromosome 6,58 and an isochromosome ofthe glaucoma. Trans OphthalmolSoc UK 1978; 98: 213-5. 9 Rolled J. Arch Keratites, degenerations et opacites Corneennes long arm of autosome 6.59 The genetics of hereditaires et familiales. Arch Ophthalmol (Paris) 1933; 50: Rieger's anomaly is less clear, though there 160-91. 10 Goldstein J, Cogan D. Sclerocornea and associated congenital certainly are pedigrees with autosomal dominant anomalies. Arch Ophthalmol 1962; 67: 99-106. transmission of the In the 11 Howard R. Abrahams I. Sclerocornea. AmJ7 Ophthalmol 1971; eye defect.2223 absence 71:1254-60. ofan offspring study ofisolated cases the propor- 12 Elliot J, Feman S, O'Day D, Garber M. Hereditary sclero- tions due to genetic and other causes cannot be cornea. Arch Ophthalmol 1985; 103: 676-9. 13 Kanai A, Wood T, Polack F, Kaufman H. The fine structure apportioned, and the precise contribution of new of sclerocornea. Invest Ophthalmol Vis Sci 1971; 10: 687-94. mutations cannot be quantified. 14 Kolbert G, Seelenfreund M. Sclerocornea, anterior cleavage http://bjo.bmj.com/ syndrome, and trisomy 18. Ann Ophthalmol 1970; 2: 26-30. The genetic counselling problems in these 15 Burian H, Braley A, Allen L. Visibility of the ring of Schwalbe families are evident from pedigree 3, where the and the trabecular zone. Arch Ophthalmol 1955; 53: 767-82. 16 Forsius H, Eriksson A, Fellman J. Embryotoxon corneae mother (12) had subtle abnormalities confined to posterius in an isolated population. Acta Ophthalmol (K-bh) the eyes but her children, who might have been 1964; 42: 42-9. 17 Axenfeld T. Embryotoxon corneae posterius. Ber Dtsch predicted to be at low risk, have inherited Ophthalmol Ges 1920; 42: 301-2. Rieger's and Peters' anomalies. In pedigree 1 the 18 Waring G, Rodrigues M, Laibson P. Anterior chamber cleavage syndrome. A stepladder classification. Surv mother's eye problems are mainly microcornea Ophthalmol 1975; 20: 3-27. on September 29, 2021 by guest. Protected copyright. and cataract, and yet she is obviously a gene 19 Rieger H, Beitrage zue Kenntnis seltener Missbildungen der Iris. II. Uber Hypoplasie des Irisvorderblattes mit carrier whose children have Peters' and Rieger's Verlagerung und Entrundung der Pupille. Graefes Arch Clin anomalies. Even with the lesson of pedigree 3 in Exp Ophthalmol 1935; 133: 602-35. 20 Falls H. A gene producing various defects of the anterior mind it would have been very difficult on seeing segment of the eye. AmJ7 Ophthalmol 1949; 32: 41-52. this woman to have predicted a 50% offspring 21 Wolter JR, Sandall G, Fralick B. Mesodermal dysgenesis of anterior eye: with partially separated posterior embryo- risk for her. In view of the hypodontia in toxon. J Pediatr Ophthalmol Strabismus 1967; 4: 41-6. pedigree 2 it is easier to say that the condition in 22 Henkind P, Siegel I, Carr R. Mesodermal Dysgenesis of the anterior segment: Rieger's anomaly. Arch Ophthalmol 1965; this family is Rieger's syndrome. However, the 73: 810-7. mother's (12) problems are very subtle, and, as 23 Pearce W, Kerr C. Inherited variation in Reiger's malforma- tion. BrJ Ophthalmol 1965; 49: 530-7. with pedigrees 1 and 3, accurate predictions as to 24 Chisholm I, Chudley A. Autosomal dominant iridogoniodys- the offspring risk would have been very difficult genesis with associated somatic anomalies: four-generation family with Rieger's syndrome. BrJrOphthalmol 1983; 67: before the birth of her first affected child. 529-34. It is probable that the mothers in each of these 25 Busch G, Wieskopf J, Busch K. Dysgenesis mesodermalis et ectodermalis Rieger oder Rieger' sche Krankheit. Klin three pedigrees are gene carriers of an autosomal MonatsblAugenheilkd 1960; 136: 512-23. dominant condition for anterior segment anoma- 26 Storimans C, Van Schooneveld M. Rieger's eye anomaly and persistent hyperplastic primary vitreous. Ophthalmic lies. In pedigrees 1 and 3 the lesions are without _ Paediatr Genet 1989; 10: 257-62. extraocular abnormalities, like the pedigrees 27 Rieger H. Erbfragen in der Augenheilkunde. Graefes Arch Clin Exp Ophthalmol 1941; 143: 277-99. reported by Fitch and Kabak3' and Pearce and 28 Mathis H. Zahnunterzahl und Missbildungen der Iris. Kerr.23 The resulting eye defects in our families Z Stomatol 1936; 34: 895-909. 29 Shields B. Axenfeld-Rieger syndrome: a theory of mechanism are remarkably variable, and these three pedi- and distinctions from the iridocorneal endothelial syn- grees serve to emphasise the variability of mani- drome. Trans Am Ophthalmol Soc 1983; 81: 736-84. 30 Hoskins D, Shaffer R. Rieger's syndrome: a form of irido- festations that this autosomal dominant gene corneal mesodermal dysgenesis. J Pediatr Ophthalmol rise to. While further the Strabismus 1972; 9: 26-30. gives complicating 31 Fitch N, Kaback, M. The Axenfeld syndrome and the Rieger situation for the genetic counsellor, these pedi- syndrome. J Med Genet 1978; 15: 30-4. Heterogeneity in dominant anterior segment malformations 597

32 Wesley R, Baker J, Golnick A. Rieger's syndrome (oligodontia corneal pigmentation and fibrous proliferation by iris and primary dysgenesis of the iris): clinical features and melanocytes. Arch Ophthalmol 1981; 99: 1232-8. report an case. .7 of isolated Pediatr Ophthalmol Strabismus 46 Reese A, Ellsworth R. The anterior chamber cleavage syn- Br J Ophthalmol: first published as 10.1136/bjo.75.10.591 on 1 October 1991. Downloaded from 1978; 15:67-70. drome. Arch Ophthalmol 1966; 75: 307-18. 33 Frandsen E. Rieger's syndrome combined with oligodontia 47 Boel M, Timmermans J, Emmery L, Dralands G, Frvns J, van and finger deformity. Acta Ophthalmol (Kbh) 1963; 41: 757- der Berghe H. Primary mesodermal dysgenesis of the cornea 67. (Peters' anomaly) in two brothers. Hum Genet 1979; 51: 237- 34 Jorgenson R. Levin S. Cross H. Yoder F. Kelly T. The Rieger 40. syndrome. AmjMed Genet 1978; 2: 307-18. 48 Cross H. Penetrance of variability in anterior chamber malfor- 35 Schmidt-Rederman B, Vogt J. Hypoplasie der Arteria mations. Birth Defects 1979; 15: 131-44. pulmonalis beim Rieger-Syndrom. Klin Padiatr 1976; 188: 49 Kresca L, Goldberg M. Peters' anomaly: dominant inherit- 554-7. ance in one pedigree and dextrocardia in another. 7 Pediatr 36 Summit R, Hiatt R, Duenos D, Johnson W. Mesectodermal OphthalmolStrabismus 1978; 15: 141-6. dysplasia of the iris and the cornea, mental retardation and 50 DeRespins P, Wagner R. Peters' anomaly in a father and son. myopathy: a sporadic case. Birth Defects 1971; 8: 129-35. Amnj Ophthalmol 1987; 104: 545-6. 37 GassIer H, Berthold H. Ein Beitrag zur Ektodermalen 51 Cibis G, Waeltermann J, Harris D. Peters' anomaly in Dysplasie aus Ophthalmologischer Sicht. Klin Monatsbl association with ring 21 chromosomal abnormality. Am.7 Augenheilkd 1960; 136: 52-65. Ophthalmol 1985; 100: 733-4. 38 Kivlin J, Fineman R, Crandall A, Olson R. Peters' anomaly as 52 Bateman B, Maumenee I, Sparkes R. Peters' anomaly associ- a consequence of genetic and nongenetic syndromes. Arch ated with partial deletion of the long arm of chromosome 11. Ophthalmol 1986; 104: 61-4. AmJ7 Ophthalmol 1984; 97: 11-5. 39 Hittner H, Kretzer F, Antoszyk J, Ferrall R, Metha R. 53 Brear R, Insler M. Axenfeld's syndrome associated with Variable expressivity of autosomal dominant anterior seg- systemic abnormalities. Ann Ophthalmol 1985; 17: 291-4. 54 Donaldson D. ment mesenchymal dysgenesis in six generations. Am 7 Feingold M, Shiere F, Fogels H, Rieger's Ophthalmol 1982; 93: 57-70. syndrome. Pediatrics 1969; 44: 564-9. 55 McKusick V. Mendelian inheritance in man. 8th ed. Baltimore: 40 Salmon J, Wallis C, Murray A. Variable expressivity of Johns Hopkins University Press, 1988. autosomal dominant microcornea with cataract. Arch 56 Forsius H. Visibility of anterior border-ring of Schwalbe in Ophthalmol 1988; 106: 505-10. congenital corneal anomalies: tumours of the limbus 41 Green J, Johnson G. Congenital cataract with microcornea and and dental anomalies. Acta Ophthalmol (Kbh) 1963; 41: Peters' anomaly. Ophthalmic Paediatr Genet 1986; 7: 187-94. 97-107. 42 Duke-Elder S. System of ophthalmology. St Louis: Mosby, 57 Stathacopoulus R, Bateman B, Sparkes R, Hepler R. The 1964; 3: 29-32. Rieger syndrome and a chromosome 13 deletion. I Pediatr 43 Johnston M, Noden D, Hazelton R, Coulombre J, Coulombre Ophthalmol Strabismus 1987; 24: 198-203. A. Origins of avian ocular and periocular tissues. Exp Eye 58 Heinemann M, Breg R, Cotlier E. Rieger's syndrome with Res 1979; 29: 27-43. pericentric inversion of chromosome 6. Br Ophthalmol 44 Bahn C, Falls H, Varley G, Meyer R, Edelhauser H, Bourne 1979; 63: 40-4. W. Classification of corneal endothelial disorders based on 59 Tabbara K, Khouri F, Der Kaloustian V. Rieger's syndrome neural crest origin. Ophthalmology 1984; 91: 558-63. with chromosomal anomaly. Can]7 Ophthalmol 1973; 8: 488- 45 Snip R, Green R, Kreutzer E, Hirst L, Kenyon K. Posterior 91. http://bjo.bmj.com/ on September 29, 2021 by guest. Protected copyright.