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Home , Hypertropia, Nystagmus, Retinitis pigmentosa

Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

British Journal of , 1984, 68, 421-431

A of congenital retinal dystrophy and palsy-a subset of Leber's amaurosis

A. T. MOORE AND D. S. I. TAYLOR From the Hospitalfor Sick Children, Great Ormond Street, London WCJN3JH

SUMMARY Three children who presented in infancy with a severe visual defect and absent or barely recordable electroretinograms, with relatively well preserved visually evoked cortical potentials, were subsequently found to have vertical and horizontal saccade palsies with head thrusts but relatively good . These children, who were clearly different from other infants with congenital retinal dystrophy, were also developmentally delayed and had systemic motor and speech defects, but their visual prognosis was relatively good. The recognition of their saccade palsy was delayed because their poor visual attention in infancy was ascribed purely to the tapetoretinal degeneration. We consider these patients represent a clear subset of those patients who are diagnosed as having congenital retinal dystrophy or Leber's amaurosis.

Congenital retinal blindness (Leber's amaurosis), in the first few months of life. Other ocular abnor- which is a common cause of blindness in children, is malities such as , , and an inherited retinal dystrophy of variable severity. are often seen in older children. Between 10% and 18% of children in institutions for Congenital retinal blindness (CRB) has been the blind suffer from this condition, which is thought reported in association with various systemic con- http://bjo.bmj.com/ to be autosomal recessive in its inheritance.'2 The ditions. Mental subnormality, psychiatric disturb- usual presentation is with suspected blindness or poor ance, neurodevelopmental disorders, and certain vision with from birth or in the first few structural abnormalities ofthe months of life. There may be , and eye (CNS) are said to be commoner in this condition than poking (digito-ocular sign of Franceshetti)3 is some- in the general population. The incidence of these times seen. There is usually nystagmus or roving eye abnormalities in CRB is, however, difficult to movements, and the reactions may be sluggish determine because of the differences in patient on September 30, 2021 by guest. Protected copyright. or absent. The is often normal or subtly selection in different studies and also because of the abnormal when the child is examined in the first few different referral patterns to the various centres. months of life, but later a variety of abnormal fundus Alstrom and Olson' in a large series from Sweden appearances may be seen. The fundus is often found no association with neurological disorders, but albinotic; there may be a diffusely granular appear- their cases were drawn from a school for mentally ance to the retinal pigment epithelium, and white normal blind children, and therefore their results punctate spots are sometimes seen in the periphery.4 were biased against neurological or psychiatric dis- There may be a scattered pigmentary change, retinal order. Schappert-Kimmijser et al.2 found major arteriolar narrowing, and pallor of the optic discs. In neurological and psychiatric abnormalities in 25% of some older patients the fundus may resemble that in affected children in a large study from Holland. Other typical pigmentosa. The appearance of optic smaller studies4' -II have found a higher incidence disc oedema5 and 'macular "'7 has also of such abnormalities, but again this may reflect a been reported, and affected children are often hyper- bias in selection. Vaizey et al.,' for instance, base metropic. The diagnosis of congenital retinal dys- theirstudyon patients referred to a national paediatric trophy is made by the finding ofan absent or markedly neurological centre. Two recent reports'2 '3 found no reduced electroretinogram (ERG) in a child with major increase in the incidence of subnormality or blindness or poor vision and nystagmus from birth or in this condition. Although Correspondence to D. S. 1. Taylor, FRCS. specific structural abnormalities of the CNS are 421 Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

422 A. T. Moore and D. S. 1. Taylor

uncommon in CRB, there appears to be a definite condition, or there are separately inherited diseases association with hypoplasia of the .8 12 14 accounting for the variation. Nickel and Hoyt 12 reported the results of CT scanning Congenital retinal blindness is therefore seen in in 31 patients with CRB. A structural defect of the association with several systemic disorders. We report CNS was found in only three cases, and in each case three cases in which a congenital retinal dystrophy is the lesion was hypoplasia of the cerebellar vermis. associated with an ocular motor disorder similar to Dekaban 14 found hypoplasia of the cerebellar vermis ocular motor apraxia.

Fig. b1h http://bjo.bmj.com/ and immature cortical neurons at post-mortem exam- ination of a 3-year-old boy with CRB. Childhood retinal dystrophies have also been reported in association with renal abnor- malities.8' 14-22 Senior and others'5 and Loken and others "' independently first described the association of a recessively inherited renal dysplasia, juvenile , or medullary cystic disease and a on September 30, 2021 by guest. Protected copyright. tapetoretinal degeneration indistinguishable from Leber's amaurosis. The renal and retinal abnor- malities have also been described in association with another recessively inherited condition-congenital hepatic fibrosis.23 Various authors have reported great variations in the level of vision in CRB. All of Nickel and Hoyt's'2 31 patients had vision estimated at the level of light perception or worse. Other authors' 281113 have reported a small group of children who have reason- ably good central vision when old enough to be formally tested, despite apparent blindness and a reduced or absent ERG in infancy. This relatively ritg. IC high level of acuity has been attributed to preserved central visual Figs. la,b The rightfundus ofcase I at22 months shows function, with widespread peripheral the very slightly pale right and its macula. The retinal abnormalities accounting for a reduced ERG. arterioles were probably within normal limits. c: Case 1: the Clearly there is either great heterogeneity within one fluorescein angiogram was normal. Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

A syndrome ofcongenital retinal dystrophy andsaccadepalsy-a subset ofLeber's amaurosis 423

Case reports ampicillin in pregnancy, for recurrent parotid swelling, but the pregnancy was otherwise normal. CASE 1 The birth was normal, at term, and the birth weight This boy was the first child of healthy, unrelated was 8 lb 2 oz (3685 g). Intubation and intermittent parents. His mother received several courses of ventilation were required for 1 l/2minutes after birth, V E P

Case 0 Age 2y

Case 3 Age 2y http://bjo.bmj.com/ Case 2 Age 4y on September 30, 2021 by guest. Protected copyright. Case 1 Age 5y

St im. Stim. Time marker 25 ms Fig. 2 Electroretinogram (ERG) recordedfrom an electrodeplaced on the bridge ofthe nose and visualevokedpotential (VEP) recordedfrom the midoccipital region (flash stimulated to both eyes simultaneously while open). Top traces (M. S.) normal. Responsesfrom 2-year-old childfor comparison. Case3, case2, and case I show no clear retinal response, but a cortical response ispresent, though the usual earlier components are rathersmall, especially in case 1, butare in keeping with some preservation offunction ofthe central visualpathways to the brain. Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

424 A. T. Moore and D. S. I. Taylor and intensive care and nasogastric feeding were count, ESR, urea and electrolytes, liver function required for the first 10 days. Neonatal jaundice was tests, plasma amino acids, toxoplasma, herpes and treated with phototherapy. rubella titres, serum thyroxine, pyruvate and lactate, The mother, a trained nurse, suspected that he had creatinine phosphokinase and immunoglobulins, poor vision at 6-8 weeks; nystagmus was noted at 12 urinary aminoacids, urinary reducing substances, weeks, and photophobia was present for the first 4 midstream urine, nitroprusside test. There were no months. At 12 weeks he was admitted to the local metachromatic granules on urine examination and no children's hospital for investigations. He was found vacuolated lymphocytes in the peripheral blood. Skull to have poor vision, optic atrophy, and develop- x-ray, chest x-ray, and intravenous pyelogram were mental delay. A raised cytomegalovirus (CMV) titre normal. An electromyogram and nerve conduction was found and thought to be the factor responsible studies were also normal. The CMV titres were 1 in for his condition. 64. CT scan (Fig. 3) showed a large fourth ventricle He was first seen at the Hospital for Sick Children and prominent cisterna magna, and an appearance at 22 months. His parents had noticed some improve- consistent with hypoplasia of the cerebellar vermis. ment in his vision over the preceding 12 months. On When examined at the age of 4 years he appeared examination he could reach out for objects in all parts to have good visual acuity, and there was a horizontal of his visual fields; there was bilateral 'pendular and vertical saccade palsy, with head thrusts similar nystagmus' with full random eye movements. Pursuit to those seen in ocular motor apraxia used on refixa- movements were mildly impaired, but there was a tion. The ERG was again absent. He was last seen in gross defect in saccadic eye movements. Pupil 1982, at the age of 8 years, when the visual acuity was reactions were normal, and fundus examination 6/18 in each eye with hypermetropic correction. There showed slightly pale discs, rather featureless maculae, was 'pendular' nystagmus without fast phases and an and mild peripheral retinal pigment epithelial dis- alternating divergent squint with left . turbance; the fluorescein angiogram was normal (Fig. Colour vision was normal. The visual fields were 1). There was no recordable ERG, and the visual reduced to 300 in each eye. Both discs were pale with evoked response (VER), though present, was of low attenuated vessels, and there was a mild peripheral amplitude, and no early components were detectable retinal pigment epithelial disturbance but no pigment (Fig. 2). clumping. The ocular movements were again General examination revealed that he was on the abnormal. There was difficulty in carrying out smooth 50th percentile for height and weight and the 75th pursuits, and there was an almost total saccadic

percentile for head circumference. There was gener- defect. There appeared to be great difficulty in in- http://bjo.bmj.com/ alised hypotonia, but no other abnormal physical itiating eye movements, and closure and head signs. Psychological assessment showed him to be thrusts were present on attempted refixation. Opto- functioning at the 16-month level on a scale for kinetic nystagmus was absent, but doll's head move- partially sighted children (Reynell-Zinkin scale). The ments were full. General assessment revealed muscle following investigations were normal: full blood hypotonia, severe speech dyspraxia, generalised dis- on September 30, 2021 by guest. Protected copyright. I

Figs. 3a,b The CTscans ofcase I at 22 months showed hypoplasia of the cerebellar vermis..

Fig. 3g.Fig. .3h Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

A syndrome ofcongenital retinal dystrophy andsaccade palsy-a subset ofLeber's amaurosis 425

i-ic. 4(i HIoi 4f1l Figs. 4a,b The right optic disc and macula ofcase 2 at 8½ months. Apartfrom a mild appearance ofoptic discswelling the fundi were normal.

turbance of motor control, disequilibrium, and low brother's with a marked abnormality of saccadic eye normal intelligence. movements. There were no large head thrusts, but head movements were used in refixation in the

CASE 2 absence of normal . The ERG was repeated, http://bjo.bmj.com/ This male child, the younger sib of case 1, was born and there was a very low amplitude response of 1 or 2 after a normal pregnancy and delivered at term. On the second day he developed respiratory stridor and bursts of rapid respiration, especially when handled, but this soon settled. The neonatal period was other- wise uneventful. His mother noticed nystagmus and

poor vision soon after birth, and for the first six on September 30, 2021 by guest. Protected copyright. months he showed little visual attention. He was first seen at the Hospital for Sick Children at 81/2 months. There was 'pendular' nystagmus, but he would follow a light, and pupil reactions were normal. Retinoscopy revealed 9 dioptres of hypermetropia in each eye. Fundus examination was normal (Fig. 4), apart from an appearance of mild disc swelling. Fluorescein angiography showed an area of poor choroidal filling below and temporal to the optic disc, but was other- wise normal (Fig. 5). An ERG was ofvery low ampli- tude (2 ,uV), and the visual evoked response was normal (Fig. 6). General examination revealed generalised hypotonia and developmental delay. Similar investigations to those performed in his sibs were all normal apart from the CT scan (Fig. 6) which showed a similar appearance to his sib. Fig. 5 Thefluorescein angiogram showed a transient When reassessed at the age of 2 years he was found choroidalfilling defect in the right eye but was within normal to have an ocular motor abnormality similar to his limits. Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

426 A. T. Moore and D. S. I. Taylor

Figs. 6a,b The CTscan ofcase 2 showed cerebellarhypoplasia.

[ig. (6i I-1i. Ot) ,uV. He was last seen at the age of 5 years, when his reduced to about 45°. Fundus examination revealed corrected vision was 6/18 right and 6/36 left. There normal discs and vessels but a mild peripheral retinal was an alternating divergent squint, but no nystagmus pigment epithelial disturbance and an unusual white in the primary position. Pursuit movements were deposit around both maculae (Fig. 8). General assess- normal, but there was a marked abnormality of ment revealed low normal intelligence, a dyspractic horizontal and vertical saccadic movements. There speech abnormality, and disequilibrium and motor was difficulty in initiating saccades, and attempts at abnormalities similar to those of his sib. refixation were accompanied by head movements in advance of eye movements (Fig. 7). The normal fast CASE 3 component ofoptokinetic nystagmus was not elicited. This male child was born after a normal pregnancy to Doll's head movements were full. Visual fields were unrelated parents by a normal delivery, and weighed http://bjo.bmj.com/ on September 30, 2021 by guest. Protected copyright.

_ 1~~,;A m _ ~ ~ Fig. 7b He has already thrust his headfar to the right and is Fig. 7a Case 2, showing him about to look to the rightfrom returning it to the left whilst the eyes achieve their new the left. position. Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

A syndrome ofcongenital retinal dystrophy and saccade palsy-a subset of Leber's amaurosis 427

Fig. 8at Fg. 8h Figs. 8a,b The maculae ofcase 2 at 2 years oldshowed a white deposit around thefo,ea in the neural . 6 lb 13 oz (3090 g) at birth. He had a brief cyanotic other eye was covered. Nystagmus was still present, attack soon after birth, but the neonatal period was but on this occasion he was found to have an oculo- otherwise normal. There was no relevant family motor abnormality with poor horizontal saccades and history. At 6 months the health visitor noticed obvious horizontal head thrusts similar to those seen nystagmus and poor visual attention. At 2 months he in oculomotor apraxia (Fig. 10). Vertical movements was noticed to shake his head from side to side; he were normal. Spinning resulted in only a tonic devia- was also showing signs of poor motor development. tion of the eyes. Fundus examination and fluorescein At 4 months he was admitted for investigation of angiogram were normal. An ERG carried out with

poor vision and developmental delay. He was found skin electrodes with the child awake showed an absent http://bjo.bmj.com/ to have 'roving eye movements' with poor fixation. response, but a second ERG carried out under Pupil reactions to light were sluggish, and spinning general anaesthetic using a gold foil electrode in the produced only a tonic deviation of the eyes. Fundus lower fornix revealed a low amplitude response examination and a fluorescein angiogram were (30 [V-normal 150 [tV). General examination normal (Fig. 9). The ERG was absent, and the VER revealed hypotonia, generalised motor delay, and was of reduced amplitude (Fig. 2). General examina- poor intellectual performance. tion revealed hypotonia and delayed motor He was last seen at the age of 51/2 years. Because of development. mental retardation it was not possible to test his on September 30, 2021 by guest. Protected copyright. The following investigations were all normal: full visual acuity formally, but he could reach out for blood count, ESR, urea and electrolytes, serum small objects in all parts of the of each eye. creatinine, liver function tests, plasma amino acids, To confrontation his visual fields were full, and he plasma proteins, 'immunoglobulins, serum mag- was able to match coloured objects accurately. There nesium, phosphate and alkaline phosphatase, was no nystagmus or squint, but both reacted creatinine phosphokinase, toxoplasma, rubella, very sluggishly to light. There was difficulty in per- cytomegalovirus, and herpes (TORCH) screen, forming horizontal pursuit movements and a marked VDRL, skull x-ray, and chest x-ray. The serum abnormality of horizontal saccades. Vertical move- pyruvate and lactate were minimally raised but ments were reasonably full. Obvious head thrusts thought to be of no significance. There were no were present on attempted refixation. No optokinetic metachromatic granules on urine examination and no nystagmus could be elicited. Fundus examination vacuolated lymphocytes in the peripheral blood. CT showed mild peripheral retinal pigment epithelial scan was normal. A provisional diagnosis of Leber's disturbance but was otherwise normal. He still has amaurosis was made. very poor motor development; he is able to support When he was examined again at the age of 3 years his weight but unable to walk; he has developed his vision was found to be better than anticipated. He no speech, but has normal hearing, and is severely would reach out for small objects, even when one or intellectually subnormal. Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

428 A. T. Moore and D. S. 1. Taylor

1-iti. '3a Fic. 9bI origin. Most reports have emphasised the poor visual prognosis in CRB, but some studies have reported patients with relatively good visual acuity, when they are old enough to be formally tested.' 28x 3 In Alstrom and Olson's study' 79% of cases had visual acuity of hand movements or worse and only 5% had visual 0. 1 or better. There appeared to be a acuity of (6/60) http://bjo.bmj.com/ decline in vision in later life, which was not related to the development of opacities. In the study of Vaizey et al.8 6 of 27 children with CRB retained reasonable vision, and 5 could be formally tested. Three had vision between 6/36 and 6/60 and 2 had vision of 6/12 or better. Stanley et al.'33were able to assess visual acuity in 16 patients in their study and 4 had an acuity of 20/200 or better. Although most on September 30, 2021 by guest. Protected copyright. children with CRB have poor vision, a minority will develop reasonably good central vision despite having an extinguished or subnormal ERG. This indicates that CRB is a heterogeneous condition or, perhaps more likely, that it is a group of disorders. All three of our patients fall within this group, and they are not r1 I (. 9c the same patients reported by Vaizey et al. from this Fig. 9a The macula ofcase 3 at 4 months was normal. hospital.8 b,c: Thefluorescein angiogram was normal. In 1952 Cogan24 described a congenital ocular motor abnormality (COA) which he termed ocular Discussion motor apraxia, which is characterised by impairment of horizontal gaze with preservation of full random These three patients are of interest firstly because eye movements. Conspicuous head thrusts are they are part of a subgroup of patients with CRB who present on attempted horizontal gaze. Vertical gaze retain useful vision, and secondly because they show is usually normal. Horizontal saccades are absent or an association ofretinal dystrophy with an oculomotor abnormal, and the fast phase of optokinetic nystag- disorder which is also thought to be congenital in mus is absent horizontally. In children with large Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

A syndrome ofcongenital retinal dystrophy andsaccadepalsy-a subset ofLeber's amaurosis 429

Fig. 10 Case3. Left: he is about to make a refixation to the left. Right: he has thrust his headfar to the left and is making a correcting thrust to the right to get the eyeposition on target.

obvious head thrusts the diagnosis is not difficult, but cerebellum. An ocular motor defect similar to COA in other cases the abnormality of head and eye move- has been seen in spinocerebellar degeneration29134344- ments may be more subtle and very variable. In and in a closely related condition olivoponto- infancy the saccade disorder may easily be missed .' It has also been reported and the child suspected of having very poor vision in association with another cerebellar disorder, because of the absence of visually elicited eye move- Pelizaeus-Merzbacher disease.34 These conditions ments. The condition is commoner in boys, but it also can be differentiated from COA by the age of onset occurs in girls.25--3' It has been reported in and other associated clinical features. sibs,262932 identical twins,33 and in two successive In our three cases it is unlikely that the oculomotor generations.27 It is thought to be inherited both as a defect is due to a constricted visual field giving rise to

sex-linked and autosomal recessive condition, though poor visual fixation, because even reflex saccades http://bjo.bmj.com/ some cases are sporadic.32 were abnormal. Initially the condition was thought to be benign It is interesting that both COA and CRB have been and to improve with age, as it has only occasionally reported in association with hypoplasia of the been seen in adults. Some reports have indicated an cerebellar vermis, and in addition cerebellar disease association of COA with neurological and other and tapetoretinal degeneration coexist in several con- systemic disorders; these have been reviewed by ditions affecting children. Carpenter et al.47 reported

Rendle Short32 and Cogan et al.34 Neurological three sibs under the age of 2 years with olivo-ponto- on September 30, 2021 by guest. Protected copyright. abnormalities have included mild hemiplegic , cerebellar atrophy, who had fundus appearances mental retardation, and delayed motor development. consistent with a tapetoretinal degeneration, though Several patients have shown structural abnormalities no ERG was performed no pathological findings on of the CNS on neuroradiological investigation. the eye were available. De Jong et al.48 reported Agenesis of the corpus callosum,3"35 hamartoma of three children under the age of 4 years with OPCA, the foramen of Monro,-35 and cerebellar hypoplasia31 who had a retinal dystrophy confirmed by the presence have all been reported. Other patients, however, of an extinguished ERG. Pathological examination have had normal air encephalograms and CT ofthe eyes of one child who died at 11 months showed scans.32 34 37There have also been two reports ofCOA absence of rods and cones in the posterior retina. in patients with brain stem compression by Ryan et al.49 found abnormal retinal pigment epi- tumour.3839 Other systemic abnormalities such as thelium and photoreceptors at post-mortem examina- web toes, cleft plate, and orofacial digital syndrome tion of the eyes of two children with histologically have also been reported in the condition.34 Supra- proved OPCA. The association of OPCA and an nuclear palsies of horizontal gaze with compensatory apparently acquired tapetoretinal degeneration has head movements similar to COA have also been also been reported in adults.5" Spinocerebellar reported in ataxia telangiectasia4"14' and Wilson's degeneration has also been described in association disease,42 Huntington's chorea,43 Gaucher's with an apparently acquired form of tapetoretinal disease,' and various conditions involving the degeneration, which first appears in adult life, affect- Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

430 A. T. Moore and D. S. I. Taylor

ing the macula initially and later involving the ing which patients need further investigation to rule peripheral retina.5' 52 A retinal dystrophy indis- out systemic associations. tinguishable from Leber's amaurosis has been reported in association with Joubert's syndrome; a recessively inherited condition comprising episodic The authors express grateful thanks to Dr Ann Harden for carrying out the electrodiagnostic studies and to Yvonne Robinson and hyperpnoea, abnormal eye movements, ataxia, Josephine Lace for preparation of the manuscript. Mr Martin Johns psychomotor retardation, and hypoplasia of the provided the photographs. cerebellar vermis.53 5' Tapetoretinal degeneration Mr A. T. Moore received financial support from the T.F.C. Frost and oculomotor abnormalities have also been Charitable Trust. described in association with mitochondrial cyto- pathy, a multisystem disorder ofchildren and adults,55 References but the usual oculomotor disorder is 'ophthalmo- plegia plus'5Se and is a peripheral muscular disorder I Alstrom CH, Olson OA. Heredoretinopathia congenitalis mono- hybrida recessiva autosomalis. Hereditas 1957; 43: 1-177. affecting all modalities of eye movements. 2 Schappert-KimmijserJ, Henkes HE, van den Bosch J. Amaurosis Cogan et al.34 have reported two sibs who were congenita (Leber). Arch Ophthalmol 1959; 61: 211-8. found to have COA and normal fundi in infancy, who 3 Franceschetti A. Rubeole pendant la grossesse et cataracte con- when re-examined seven years later were found to genitale chez l'enfant; accompanee du phdnomene digito- -a oculaire. Ophthalmologica 1947; 114: 332-9. have typical pigmentary with an 4 Franceschetti A, Francois J, Babel J. Autosomal chorioretinal extinguished ERG. Ourthree cases in which diagnosis heredo degenerations with tapetoretinal predominance in chorio- of a retinal dystrophy was made before a saccade retinal heredode generations. Springfieid: Thomas, 1974: 305-29. palsy was evident confirms the association of supra- 5 Flynn JT, Cullen RF. Disc ocdema in congenital amaurosis of nuclear Leber. BrJ Ophthalmol 1975; 59: 497-502. gaze disturbance and tapetoretinal degenera- 6 Leighton DA, Harris R. Retinal aplasia in association with tion in children. Although only one of our cases had macular , keratoconus and cataract. Clin Genet 1973; typical ocular motor apraxia, it appears that these 4: 270-274. five cases represent a new subgroup ofthose disorders 7 Margolis S, Scher BM, Carr RE. Macula colobomas in Leber's which have in common abnormalities of brain stem congenital amaurosis. Am J Ophthalmol 1977; 83: 27-31. 8 Vaizey MJ, Sanders MD, Wybar KC, Wilson J. Neurological and cerebellum, supranuclear gaze disturbance, and abnormalities in congenital amaurosis of Leber. Review of 30 tapetoretinal degeneration. Klein has pointed out cases. Arch Dis Child 1977; 52: 399-40)2. that there may be a specific group of disorders with 9 Dekaban A, Carr R. Congenital amaurosis of retinal origin. cerebellar and retinal involvement,57 and Nickel and Frequent association with neurological disorders. Arch Neurol Hoyt have emphasised that the cerebellar vermis 1966; 14: 294-301. 10 Noble KG, Carr RE. Leber's congenital amaurosis. A retrospec- http://bjo.bmj.com/ begins to appear as a distinct structure at the same tive study of 33 cases and a histopathological study of one case. stage of embryogenesis (12 weeks) that active dif- Arch Ophthalmol 1978; 96: 818-21. ferentiation of the photoreceptor layer of the retina is 11 Karel I, Brachfield K, Styblova, Sedlackova E. Ophthalmological and general findings in congenital diffuse tapetoretinal degenera- taking place. 12 Both CRB and COA have individually tion. In: Brunette JR, Barbeau A, eds. Progress in neuro-oph- been reported in association with hypoplasia of the thalmology. Amsterdam: Excerpta Medica, 1968: 377-86. cerebellar vermis, and in the first two cases reported 12 Nickel B, Hoyt CS. Leber"s congenital amaurosis. Is mental here the CT scan appearances were consistent with retardation a frequent associated defect? Arch Ophthalmol 1982;

100:1089-92. on September 30, 2021 by guest. Protected copyright. cerebellar hypoplasia. 13 Stanley JH, MacDonald J, Flynn JT. Leber's congenital These three cases raise a further question about the amaurosis: a clinical study. Neuro-ophthalmology update. In: nature of the condition of Leber's amaurosis. Most Lawton-Smith J. New York: Masson, 1977: 91-7. cases are thought to be autosomal recessive in in- 14 Dekaban AS. Hereditary syndrome of congenital retinal blind- ness (Leber), polycystic kidneys and maldevelopment of the heritance, yet there is a wide variation in the severity brain. Am J Ophthalmol 1969; 68: 1029-37. of the visual loss and also in the associated systemic 15 Senior B, Friedmann Al, Braudo JL. Juvenile familial features. Are the cases reported here a genetic sub- nephropathy with tapetoretinal degeneration: a new oculorenal type, as may be those cases with renal or neurological dystrophy. Am J Ophthalmol 1961; 52: 625-33. or 16 Loken AC, Hanssen 0, Halvorsen S, Jolster NJ. Hereditary disorders, are they all part of a wide spectrum of renal dysplasia and blindness. Acta Paediatr Scand 1961; 50: disease in a single genetically determined disorder? It 177-84. is interesting in this respect that Waardenberg et al.55 17 Fairley KF, Leighton PW, Kincaid-Smith P. Familial visual reported two patients blind from birth with presumed defects associated with polycystic kidney and medullary sponge who kidney. Br MedJ 1963; 1: 1060-3. CRB, married and had two normal children, 18 Hussels IE. Congenital amaurosis and nephronophthisis: a new suggesting that there are at least two different syndrome. Birth Defects 1971; 7: 199. recessive causing this disorder. The answers to 19 Meier DA, Hess JW. Familial nephropathy with retinitis pig- these questions are of more than academic interest, mentosa: a new oculorenal syndrome in adults. Am J Med 1965; as they are important in an 39: 58-69. allowing accurate visual 20 Betts PR, Forrest-Hay 1. Juvenile nephronophthisis. Lancet and educational prognosis to be made and in predict- 1973; ii: 475-8. Br J Ophthalmol: first published as 10.1136/bjo.68.6.421 on 1 June 1984. Downloaded from

A syndrome ofcongenital retinal dystrophy andsaccade palsy-a subset ofLeber's amaurosis 431

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tclangicctaisia. Ophthiahnoloalgica 19811; 181: 33(0-3. (Kbh) 1963; 41: 317-20. on September 30, 2021 by guest. Protected copyright.