Britishlournal ofOphthalmology, 1990,74,421-426 421 The eye in the CHARGE association Br J Ophthalmol: first published as 10.1136/bjo.74.7.421 on 1 July 1990. Downloaded from

I M Russell-Eggitt, K D Blake, D S I Taylor, R K H Wyse

Abstract association (vertebral malformation, atresia of CHARGE association includes patients with at the anus, cardiac malformation, trachael fistula, least four features prefixed by the letters of the oesophageal atresia, renal and radial dysplasia, mnemonic: , Heart defects, Atresia and limb malformations) may be an expression of of the choanae, Retarded growth and develop- the same defect as the CHARGE association.7 ment, Genital hypoplasia, Ear anomalies and/ Pagon et all and subsequently several other or hearing loss. Many also have facial palsy. authors89 have included in the CHARGE We report a series identified by collaboration association cases of the Di-George syndrome. within one centre of all specialties concerned This is a disorder in development ofthe third and in the management of the CHARGE associa- fourth pharyngeal pouches, with parathyroid tion. Ocular abnormalities were found in 44 out and thymic hypoplasia, cleft palate, micro- of 50 patients with the CHARGE association. gnathia, low-set ears, and heart defects,° now Of these, 41 had 'typical' colobomata. The known sometimes to be due to a deletion in the majority had retinochoroidal colobomata with region 22q1 1 ofchromosome 22. involvement, but only 13 patients Davenport et a"l' reported a series of 15 had an defect. Two patients had atypical patients with the CHARGE association, with a iris colobomata with normal fundi. Additional similar multidisciplinary ascertainment to our features were microphthalmos in 21 patients, study. In many other reports of the CHARGE in four, in association there is a bias towards certain abnor- 12, and a vertical disorder of eye movement in malities: the 17 cases described by Hall were four ofthe 22 cases with facial palsy. We report selected on the basis of and an incidence of coloboma in the CHARGE multiple abnormalities.'2 Pagon et all described association of 86% (43/50) compared with a 21 patients all of whom had choanal atresia and/ previous cumulative reported incidence of66% or colobomata. In the most recent review of the (112/170). We believe that there may have been CHARGE association Chestler and France'3 previous underdiagnosis of colobomata in added six further cases with a bias towards children with multiple congenital abnormali- colobomata. ties. In this paper we report the incidence and range ofocular features in the CHARGE associa- http://bjo.bmj.com/ tion. Our aim was to record the largest series to Among the myriad of congenital abnormalities date and to reduce bias of ascertainment by seen in paediatric practice the grouping of cases collaboration, within one centre, ofall specialties where certain features often occur in association concerned in the management of the CHARGE is useful and often precedes understanding ofthe association. aetiology. The CHARGE association includes patients on September 29, 2021 by guest. Protected copyright. with at least four features prefixed by the letters Patients and methods of the mnemonic: Coloboma, Heart defects, This study describes the ophthalmic features of Atresia of the choanae, Retarded growth and 50 patients with the CHARGE association all of development, Genital hypoplasia. Ear anomalies whom have been seen at one centre. Ascertain- and/or hearing loss.' The diagnosis has become ment of patients, both retrospective and pros- more specific as patients with this phenotype but pective, was through a variety of specialists: a with a known aetiology, such as cat-eye syn- general paediatrician, geneticist, cardiologist, drome (partial tetrasomy 22), Di-George otorhinolaryngologist, and ophthalmologist. syndrome (deletion 22ql 1), and multiple Most cases presented as neonates requiring abnormalities due to teratogens such as retinoic major surgery for congenital heart disease, Department of are or , acid, excluded. choanal atresia, tracheo-oesophageal fistula. Hospital for Sick Most cases of CHARGE seem to be sporadic. Patients with CHARGE features were screened Children, Great Ormond Environmental or genetic causes may act during this study, if not previously, by all the Street, London similarly. Autosomal dominant pedigrees of for further features. The minimum I M Russell-Eggitt specialists D S I Taylor CHARGE give support to a genetic basis in a criterion for inclusion in our study required that minority of patients.2" The similarities between patients should have at least four of the major Department of Paediatric patients are striking, and there is considerable features in the acronym." There were 28 males Cardiology, Institute of Child Health, 30 Guilford concordance within dominant pedigrees. In 1981 and 22 females. There were 13 deaths, most Street, London WC1 Pagon et al' described this non-random series of during the first year oflife; those who died had all K D Blake features comprising CHARGE association in undergone at least three non-ophthalmic surgical R K H Wyse order that later splitting by aetiology might be procedures. Correspondence to: D S I Taylor, FRCP, FRCS, possible. Since then it has become clear that The six major systemic features of CHARGE Hospital for Sick Children, facial palsy, renal abnormalities, orofacial clefts, are presented in Table I. Facial palsy was also Great Ormond Street, London WC1N 3JH. and tracheo-oesophageal fistulae also frequently included as a major feature, as it has been Accepted for publication accompany the main features.6 previously reported in at least 40 cases and is an 26 January 1990 Warburg has suggested that the VACTERL otherwise uncommon finding in infancy. 14 422 Russell-Eggitt, Blake, Taylor, Wyse

TABLE I The initial letters ofthe acronym CHARGE are TABLE II Thefrequency ofoccurrence ofmajor ocular used to denotefeatures present in each case reported features is tabulated Br J Ophthalmol: first published as 10.1136/bjo.74.7.421 on 1 July 1990. Downloaded from Coloboma Number ofpatients Heart defect Atresia of choanae Right Left Bilateral Total Retardation of growth or development Genital hypoplasia Colobomata Ear abnormalities or deafness Iris 5 2 6 13 palsy of facial nerve Retinochoroidal 7 3 30 40 4 6 27 37 1 CHARGEp 26 H RGEp 1 2 CHARGE 27* CHAR E Microphthalmos 7 6 8 21 3* C AR Ep 28 CHARGEp Squint 17 4* CHAR E 29 CH RGE Nystagmus 12 5 CHARGEp 30 CH RGE 6 C RGE 31* CHAR Ep 7 CH R Ep 32* CH R Ep 8 CH RGE 33* C AR E 9 CH RGEp 34 CH RGE Colobomata affected the posterior segment in 10 CHA GEp 35 CH RGEp 11 HARGE 36* CHAR Ep 38/50 cases (bilateral in 32). Two additional cases 12* CHA E 37* CHAR Ep had gross microphthalmos of the fellow eye, and 13 CHA GEp 38* CHAR E 14 C RGEp 39 CH RGEp in all but seven eyes the optic disc was involved. 15 CHARGE 40* CH R E In some cases the coloboma was very subtle, 16* CHAR E 41 H RGEp 17 CHARGEp 42* CH R E but nonetheless of diagnostic importance: three 18 C ARGE 43 CH RGE patients had iris colobomata which involved 19* CHAR Ep 44* CH R E 20* CHAR Ep 45* HAR E only part of the stroma, and two patients with 21 CH RGEp 46* HAR E posterior colobomata had only a small defect in 22 CHARGE 47* CH R E 23* HAR E 48 CH RGE the retinal pigment epithelium just below and 24* CHAR Ep 49 CH RGE nasal to the optic disc. The optic disc in these 25 CHARGE 50* C AR E patients had a hyperpigmented border, especi- *Denotes female. ally temporally, and in one eye this was the only abnormality, but the fellow eye had a disc Genital abnormalities were apparent only in the coloboma with inferonasal chorioretinal thin- males. ning with scleral ectasia (Figs IA, IB). Microphthalmos was bilateral in eight patients, right sided in seven, and left in six, but Results was mild in the majority. Only one eye of three patients had no useful vision. KARYOTYPES Optic nerve hypoplasia was noted in patients Chromosome analysis was performed in 48/50 19, 30, 41, and 50. In all these cases the eye with of the patients and an abnormality in blood the hypoplastic disc was the better seeing eye,

chromosomes was confirmed only in case 36, with an acuity range of 6/6-6/18. Only patient 50 http://bjo.bmj.com/ which had an apparently balanced translocation had a pigmented optic disc border, and none had ofchromosomes 6 and 8. the double pigmented ring sign of optic nerve hypoplasia. Two patients (17 and 41) had unilateral per- OCULAR FINDINGS sistent hyperplastic primary vitreous (without a The ocular features of the individual patients are fundal view), case 17 had a 'typical' coloboma

summarised in Table II. Ocular abnormalities (that is, occurring along the embryonic fissure), on September 29, 2021 by guest. Protected copyright. were found in 44/50 patients (88%); 41 (82%) while case 41 had hypoplasia of the fellow optic of these had a 'typical' coloboma of varying disc. Patient 47 had partial upper lid colobomata, severity. Two patients had atypical iris colobo- and two cases (9 and 47) had blockage of the mata with normal fundi: case 8 had a unilateral nasolacrimal duct. upper nasal defect and case 48 had bilateral nasal One patient (18) had in association defects. with , and case 17 had spon-

Figure 1: The right optic disc ofcase 50 has a hyperpigmented border, the visual acuity is 6/6 with a -3-00 dioptre sphere. The fellow optic disc is colobomatous with inferonasal chorioretinal thinning and scleral ectasia. The acuity is 6/36 with -12 00 dioptre sphere.

Figure IA Figure IB The eye in the CHARGE association 423

Figure 2: The right eye of case 19fails to elevatefully,

especially in adduction, and Br J Ophthalmol: first published as 10.1136/bjo.74.7.421 on 1 July 1990. Downloaded from the left eye shows apparent overaction in laevoelevation. The left eye is mildly microphthalmic, with inferior corneal scarring due tofacial nerve weakness.

taneous dislocation of the . In case 25 there these patients improved in visual behaviour. was a unilateral anterior polar lens opacity. Nystagmus developed in patients 12, 20, and 49. was present in 17 patients: seven Thirty-six patients had their refraction esti- esodeviations, eight exodeviations, and two mated. Of these 19 were myopic, eight were which were initially convergent but became hypermetropic, nine were emmetropic, and 14 divergent. had more than 2 dioptres of . The Nystagmus was seen in 14 (28%). All of these Snellen acuity was recorded in only 12 cases, the had optic disc colobomata except for case 7, remainder being too young or mentally retarded. which had pallor of the retinal pigment epithe- One patient had an acuity of 2/60, and another http://bjo.bmj.com/ lium only inferonasal to normal optic discs. The had 2/36 in the better eye; the remainder of nystagmus was horizontal except in cases 2, 27, patients ranged from 6/5 to 6/18 in their better and 49. In cases 2 and 27 it was rotary, with eyes. There was no correlation between the profound hearing loss also present, while in case severity of ocular defect and mental handicap. A 49 the eye movements were initially chaotic, later more severe visual defect, even absence of light settling, with bursts of vertical nystagmus. perception, was suspected in some patients with In four cases (5, 9, 19, and 39) there was a optic disc colobomata. on September 29, 2021 by guest. Protected copyright. disorder of vertical eye movement associated with facial palsy, with deficiency of upgaze, particularly in adduction, ofthe eye contralateral Discussion to the facial nerve weakness (Fig 2). Facial palsy The major ocular feature of the CHARGE was present at birth or noted soon afterwards in association is coloboma. The reported incidence 22 cases (13 right, seven left, and two bilateral). is influenced both by ascertainment and by One additional patient, case 3, had hemifacial examination (most colobomata affect the spasm which resolved. Twenty-one of our posterior segment alone and some may be subtle patients with facial palsy had a strong Bell's defects). We report an incidence of 86% (43/50) reflex and copious tear formation. Cases 5, 35, compared with a previous cumulative reported and 49 had corneal exposure, with scarring, incidence of 66% (112/170).1-8-111315-24 In some requiring lateral tarsorrhaphy in spite of simple studies not all cases were examined by an eye ointment application. ophthalmologist, and as posterior colobomata Case 7 had a saccade palsy or oculomotor often occur without an iris defect (30/50 in our apraxia, and case 5 had a jaw winking of series) they may have been under-reported. Marcus-Gunn type. Cases 1, 19, 32, and 39 had Subtle defects in the retinal pigment epithelium narrow palpebral apertures ipsilateral to micro- or iris transillumination defects along the pre- phthalmos. Case 27 had bilateral asymmetrical sumptive line of the fetal fissure accounted for ptosis, normal sized eyes, and poor levator five of our cases and could easily have been function which required an internal sling opera- overlooked if colobomatous defects were not tion on the worse affected side. being specifically sought. Patients 10, 12, 20, 29, 32, 36, and 49 were In our series a grossly hyperpigmented optic initially thought to be blind, with no apparent disc border was observed both with and without fixing or following, and 'chaotic' eye movements. hypopigmented retinal pigment epithelium In all these cases there were bilateral optic disc (cases 38 and 50). This hypopigmentation occur- and extensive chorioretinal colobomata. All red along the presumptive line of the embryonic 424 Russell-Eggitt, Blake, Taylor, Wyse

fissure. In case 50 the fellow eye had a typical disc DVM and all had bilateral optic disc and coloboma (Fig 1). Such an optic disc appearance chorioretinal colobomata. All required major has been described previously in a family with surgery as neonates; two of them had tracheo- Br J Ophthalmol: first published as 10.1136/bjo.74.7.421 on 1 July 1990. Downloaded from microphthalmos and clinical anophthalmos, but oesophageal fistula, two had and without typical coloboma.25 As microphthalmos Nissen's fundoplication. is acknowledged as being often associated with Our two cases of atypical iris coloboma occur- coloboma, this adds to the case for 'hyperpig- red without posterior segment coloboma. This mented optic disc border' sharing a similar supports the view that these are not related to a aetiology. The peripapillary hyperpigmentation defect in closure of the fetal fissure. Franqois28 observed in our patients may be associated with considered them to be a partial due to a anomalous closure ofthe superior end ofthe fetal notch at the margin of the optic vesicle. fissure. Case 47 had notches between the inner third The majority of colobomata in our series were and outer two-thirds of the margin of the upper typical in that they were fetal fissure defects. In eyelid. This has not been previously reported in the embryo during the invagination of the optic the CHARGE association. Other reported cases vesicle a groove (the embryonic fissure) remains of lid coloboma'820 do not offer sufficient clinical open at the inferior aspect of the optic cup, information to determine whether patients had allowing entry of paraxial mesoderm which later the CHARGE phenotype. Upper lid colobomata forms the hyaloid system. At 4-5 weeks the are a well described feature of the Goldenhar- fissure begins to close centrally, with apposition Gorlin syndrome,29 while lower lid defects occur extending anteriorly and posteriorly by 6 weeks. in the Treacher Collins syndrome.30 We observed the complete spectrum of defects Persistent hyperplastic primary vitreous, seen previously described,' I 1"' encompassing iris to in two of our cases, has been described in chorioretinal coloboma with or without optic association with coloboma in trisomy 13,27 which disc involvement and microphthalmos. Visual shares many other features with CHARGE. acuity ranged in our series from light perception In the present series as in cases reported to 6/5 Snellen. elsewhere there is a notable absence of other Horizontal pendular nystagmus in the ocular abnormalities, such as anterior segment CHARGE association in two of six cases with dysgenesis and primary (only case 25 colobomata has been reported by Chestler and had a primary lens opacity). France.'3 In these cases it may be secondary Ho et al24 described a mother and her two to macular or optic nerve involvement in a children with cataract, but they had only 'CH' of coloboma. We propose that nystagmus may also CHARGE, and the was complicated be central in origin. We found our case 7 to have by diabetes. Their case 5 may have had horizontal nystagmus, no major eye defect, and CHARGE with cataract, as did case II-I reported inner ear abnormalities. Furthermore, we found by Davenport et al," though this patient may or rotary nystagmus in three vertical patients. have had cataract secondary to retinal detach- http://bjo.bmj.com/ We describe a vertical disorder of eye move- ment. Retinal detachment has been reported in ment in 4/22 cases with facial palsy, character- association with posterior colobomata and ised by defective elevation of the , with the in patients with the CHARGE associa- characteristics ofeither 'superior oblique muscle tion.4" This emphasises the need for specialist overaction' or, in one case, of 'superior rectus initial eye examination with regular follow-up. underaction'. Traction test has not been possible We excluded one patient from our series who cases to a in all exclude mechanical limitation of had facial palsy and all of the acronymous on September 29, 2021 by guest. Protected copyright. glove movement. However, central disorders of features of the CHARGE association except for ocular motility are not unexpected in a syndrome choanal atresia, as chromosome analysis showed in which congenital facial palsy and disorders of him to be trisomic for a part of chromosome 22: swallowing are major features. Vocal cord the cat-eye syndrome. The phenotypes of the paralysis has also been reported.'5 Few cases of ptosis have been reported in the TABLE III The phenotypes ofsyndromes which resemble CHARGE syndrome, and most of these are CHARGE association are tabulated with, where possible, an probably pseudoptoses associated with micro- indication ofthefrequency ofoccurrence ofindividualfeatures phthalmos or orbital asymmetry.'62224 Patient G294 D'^10 27, with true ptosis, phenotypically resembled 0 I C32-4 L V/h%7 E3x Turner's syndrome but had normal chromo- C A D A G D somes. August et al22 reported one case of ptosis H T E C E W A N T 0 A which may have been central in origin and who RE H E R R also had a disorder of eye movement, but no G Y A R G D E E R L E S mention of ocular size was made. Facial palsy has been previously reported in Heart defect *** *** * *** *** *** Ear anomaly *** *** *** * *** ** the CHARGE association,"' but as we add a Coloboma *** *** * * ** large number of cases, 22/50 (44%), it may be Atresia choanae *** ** * Genital anomaly ** * * R *** arguably included as one of the major diagnostic Retardation ** * * features. Cleft lip/palate * * * * * * Renal anomaly *** * ** * Delayed visual maturation (DVM) has been Vertebral anomaly * * ** ** * * reported in infants who are severely ill from Anal atresia * ** ** * Thymus deficient R *** * various causes, including tracheo-oesophageal fistula and chest infection,26 and in cases with an ***Very often (>50%). **Often (>30%). ocular disorder such as cataracts,26 albinism,27 *Occasional (>5%). and retinal coloboma. " Seven of our patients had R = Reported. The eye in the CHARGE association 425

TABLE IV Reported ocularfeatures in syndromes with sick neonates to specialist centres; a few may be tystemicfeatures in common with the CHARGE association diagnosed later in life. While the finding of typical colobomata is not Br J Ophthalmol: first published as 10.1136/bjo.74.7.421 on 1 July 1990. Downloaded from G29 Di specific to the CHARGE syndrome, additional 0 I C32 L V39 E3 findings such as facial nerve palsy may point to C A D A G D this diagnosis in a child with multiple abnormali- H T E C E W A N T 0 A ties. We add a description of a dysplastic optic RE H E R R disc with marked peripapillary pigmentation. In G Y A R G D EE R L E S addition two patients had atypical iris colobo- mata with normal fundi, while another had Coloboma * * * * * PHPV * upper eyelid colobomata. Epibulbar dermoids * Lid coloboma * * Ocular motility 1 Pagon RA, Graham JM, Zonana J, Yong S-L. Coloboma, disorder * * congenital heart disease, and choanal atresia with multiple Optic nerve anomalies: CHARGE association.JPediatr 1981; 99: 223-7. hypoplasia * * 2 Kaplan LC. Choanal atresia and its associated anomalies. Further support for the CHARGE association. IntJ Pediatr Otorhinolaryngol 1985; 8: 237-42. 3 Hittner HM, Hirsch NJ, Kreh GM, RudolfAJ. Colobomatous microphthalmos, heart disease, hearing loss, and mental cat-eye and CHARGE retardation - a syndrome. J Pediatr Ophthalmol Strabismus syndrome the association 1979; 16: 122-8. are remarkably similar (see Table III). Some 4 Mitchell JA, Giangiacomo J, Hefner MA, Thelin JW, Pickens as some JM. Dominant CHARGE association. Ophthalmic Paediatr patients reported CHARGE (including Genet 1985; 6: 31-6. in our series) may be mosaics for cat-eye or have a 5 Metlay LA, Smythe PS, Miller ME. Familial CHARGE small deletion ofchromosome 22 as in syndrome: clinical report with autopsy findings. AmJI Med Di-George Genet 1987; 26: 577-81. syndrome. Mosaics with normal blood chromo- 6 Oley CA, Baraitser M, Grant DB. A reappraisal of the somes have been in full the CHARGE association. J Med Genet 1988; 25: 147-56. reported trisomy 22,3' 7 Warburg M. Ocular coloboma and multiple congenital abnormality being only detected on fibroblast anomalies: the CHARGE association. Ophthalmic Paediatr culture. Genet 1983; 2: 189-99. 8 Stewart G, Young DG, Azmy AF. CHARGE association in Our case 36 with an apparently balanced neonates presenting with choanal atresia. Z Kinderchir 1987; translocation may the clue 42: 12-3. provide cytogenetic 9 Brown OE, Burns DK, Smith TH, Rutledge JC. Bilateral leading to the identification of a submicroscopic posterior choanal atresia: a morphologic and histologic deletion which could be the cause of other cases study, and computed tomographic correlation. IntJ Pediatr Otorhinolaryngol 1987; 13: 125-42. at present diagnosed as having the CHARGE 10 Rohn RD, Leffell MS, Leaden P, Johnson D, Rubio T, with normal chromosomes. Emanuel BS. Familial third-fourth pharyngeal pouch syndrome overtly syndrome with apparent autosomal dominant transmission. Ocular features may help to separate the J Pediatr 1984; 105: 47-51. different phenotypes of 11 Davenport SLH, Hefner MA, Mitchell JA. The spectrum of Di-George, VACTERL, clinical features in CHARGE syndrome. Clin Genet 1986; cat-eye, and Goldenhar-Gorlin syndromes which 29: 298-310. 12 Hall BD. Choanal atresia and associated multiple anomalies. have characteristics in common with http://bjo.bmj.com/ systemic J Pediatr 1979; 95: 395-8. CHARGE (see Tables III and IV). 13 Chestler RJ, France TD. Ocular findings in CHARGE syn- drome. Ophthalmology 1988; 95: 1613-9. 14 Bergstrom L. Syndromes associated with congenital facial paralysis. Otolaryngol Head Neck Surg 1981; 89: 336-42. CONCLUSIONS 15 Lin AE, Chin AJ, Devine W, Park SC, Zackai E. The pattern ofcardiovascular malformation in the CHARGE association. In a large series with the CHARGE association, AmJ Dis Child 1987; 141: 1010-3. we have described the spectrum of coloboma- 16 Goldson E, Smith AC, Stewart JM. The CHARGE associa- tion: how well do they do? AmJI Dis Child 1986; 140: 918- microphthalmos including subtle defects such as 21. on September 29, 2021 by guest. Protected copyright. a of the retinal infero- 17 Pardo JM, Chua C. The CHARGE association in a male pallor pigment epithelium newborn infant. Clin Pediatr 1985; 24: 531-3. nasal to the optic disc and marked peripapillary 18 Koletzko B, Majewski F. Congenital anomalies in patients Ocular disorders of with choanal atresia: CHARGE-association. EurJ Pediatr pigmentation. motility 1984; 142: 271-5. central origin also occur frequently; nystagmus 19 Leclerc JE, Fearon B. Choanal atresia and associated may be or Facial anomalies. IntJ Pediatr Otorhinolaryngol 1987; 13: 265-72. horizontal, vertical, rotary. 20 Duncan NO, Miller RH, Catlin FI. Choanal atresia and nerve palsy may be accompanied by a vertical associated anomalies: the CHARGE association. Int ocular deviation. PediatrOtorhinolaryngol 1988; 15: 129-35. 21 Cyran SE, Martinez R, Daniels S, St J Dignan P, Kaplan S. Colobomata of the posterior segment with Spectrum of congenital heart disease in CHARGE associa- associated retinal detachment may be present tion.JPediatr 1987; 110: 576-8. 22 August GP, Rosenbaum KN, Friendly D, Hung W. Hypo- without iris defect (30/50 had a coloboma of the pituitarism and the CHARGE association. J Pediatr 1983; posterior segment with normal irides). A large 103: 424-5. 23 Curatolo P, Libutti G, Brinchi V. Infantile spasms and the chorioretinal coloboma even with involvement of CHARGE association. Dev Med Child Neurol 1983; 25: 367- the optic disc may be consistent with 73. moderately 24 Ho CK, Kaufman RL, Podos SM. Ocular colobomata, cardiac good central vision, but a superior visual field defect, and other anomalies: a study ofseven cases including defect is to be expected. Refractive errors are two sibs. J MedGenet 1975; 12: 289-93. 25 Russell-Eggitt IM, Fielder AR, Levene MI, Young ID. common. Twelve of our patients have benefited Microphthalmos in a family. Ophthalmic Paediatr Genet from spectacles, and there may be ocular mor- 1985; 6: 121-8. 26 Fielder AR, Russell-Eggitt IM, Dodd KL, Mellor DH. bidity due to both meridional and strabismic Delayed visual maturation. Trans Ophthalmol Soc UK 1985; . 104: 653-61. 27 Flynn JT. In: Harley RD, ed. Pediatric ophthalmology. 2nd ed. It is important for paediatricians to be aware of Philadelphia: Saunders, 1983; 1:13-4. the ophthalmic features ofthe CHARGE associa- 28 Franqois J. Colobomatous malformations. Int Ophthalomol Clin 1968; 8: 797-876. tion, since some, such as choroidoretinal 29 Mansour AM, Wang F, Henkind P, Goldberg R, Shprintzen coloboma, may be occult until complicated by R. Ocular findings in the facioauriculovertebral sequence (Goldenhar-Gorlin syndrome). AmJ7 Ophthalmol 1985; 100: retinal detachment. Ophthalmologists should be 555-9. aware of the potential systemic associations of 30 Collins ET. Case with symmetrical congenital notches in the outer part ofeach lower lid and defective development of the coloboma. Patients do not necessarily present as malar . Trans Ophthalmol Soc UK 1900; 20: 190. 426 Russell-Eggitt, Blake, Taylor, Wyse

31 Lessick ML, Szego K, Wong PKW. Trisomy 22 mosaicism discordant monozygotic twins: a case report and review of with normal blood chromosomes. Clin Pediatr (Phila) 1988; the literature. AmJ Med Genet 1987; 28: 103-9. 27:451-4. 36 Evans JA, Reggin J, Greenberg C. Tracheal agenesis and

32 Schinzel A, Schmid W, Fraccaro H, et al. The 'cat eye associated malformations: a comparison with tracheoeso- Br J Ophthalmol: first published as 10.1136/bjo.74.7.421 on 1 July 1990. Downloaded from syndrome': dicentric small marker chromosome probably phageal fistula and the VACTERL association. Am Med derived from a no. 22 (tetrasomy 22pter -> qI 1) associated Genet 1985; 21: 21-34. with a characteristic phenotype. Hum Genet 1981; 57: 148- 37 Weaver DD, Mapstone CL, Yu P-i. The VATER association. 58. AmJ Dis Child 1986; 140: 224-9. 33 Barakat AY, Butler MG. Renal and urinary tract abnormalities 38 Taylor A. Autosomal trisomy syndromes. A detailed study of associated with chromosome aberrations. Int Pediatr 27 cases of Edwards syndrome and 27 cases of Patau's Nephrol 1987; 8: 215-26. syndrome. Med Genet 1968; 5: 227. 34 Tovo PA, Davi G, Fraceschini P, Delpiano A. Thymic 39 Lillquist K, Warburg M, Andersen SR, Hagerstrand I. hormone dependent immunodeficiency in an infant with Coloboma of the iris, ciliary body and in an infant partial trisomy of chromosome 22. Thymus 1986; 8: with oesophago-tracheal fistula and congenital heart defects. 313-8. An unknown malformation complex. Acta Paediatr Scand 35 Boles DJ, Bodurtha J, Nance WE. Goldenhar complex in 1980; 69: 427-30. http://bjo.bmj.com/ on September 29, 2021 by guest. Protected copyright.