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The prenatal and postnatal development of the eye is determined by complex interactions between a number of genes, their products, and certain environmental factors.1,2 Since each eye is influenced by precisely the same processes as its fellow, mutations in regulatory genes usually lead to symmetric phenotypes. In this report, we describe two siblings of Asian ethnicity, born to unrelated parents with no family history of ocular disease, who have an unusual bilateral retinal dystrophy associated with very asymmetrical ocular growth.
Sib 1 was an 8 year old boy with epilepsy who had been born at term after an uneventful pregnancy. Pendular nystagmus had been noted soon after birth and his visual acuity in each eye was 3/60; refraction −17.00 DS right, plano left. Anterior segment examination was unremarkable with normal intraocular pressures. Examination of the right eye (Fig 1A and B) revealed generalised retinal pigment epithelial and choroidal atrophy, a macula “coloboma,” sheathed and occluded retinal vessels inferotemporally, and a shallow inferior longstanding retinal detachment with subretinal fibrosis. The left eye appeared similar; however there was no macula abnormality. By ultrasound, the axial length and ocular volume were 26.70 mm and 9.9 ml right, 20.70 mm and 4.6 ml left respectively.
Sib 2 was a 6 year old girl born at term with no significant past medical history. Her corrected visual acuity was 3/60 in each eye; refraction −17.00 DS right, plano left. Anterior segment examination was normal. Funduscopy of the right eye revealed a “macula coloboma,” extensive retinal pigment epithelial and choroidal atrophy, intraretinal pigment migration and preretinal fibrosis. The appearances of the left eye were similar. No retinal detachment was noted. Axial lengths and ocular volumes were 26.1 mm and 9.4 ml right, 20.7 mm and 4.6 ml left, respectively.
Electrophysiology was performed on both children based on the ISCEV standards for adults, but initially using surface electrodes on the lower eyelids. No definite ERG response could be recorded from the emmetropic left eye of either child (even with high intensity stimulation or photopic flicker stimulation with averaging), a finding consistent with severe generalised dysfunction involving rod and cone photoreceptors. The electrical responses of both children's myopic fellow eye showed a milder degree of dysfunction: there were reduced b:a ratios in both scotopic and photopic responses which, together with the abnormal 30 Hz flicker ERGs, suggest a mid-retinal locus affecting post-phototransductional cone and rod systems.3 The skin recordings obtained with surface electrodes were confirmed under anaesthesia using gold foil corneal electrodes.
It is reasonable to conclude that these two siblings represent original probands with a novel inherited, probably autosomal recessive, retinal dystrophy. The particularly interesting feature of this disorder is the asymmetry of the axial lengths and ocular volumes of the eyes, rare in genetically determined ocular diseases. Indeed, we are aware of only one other report that identifies ocular asymmetry in association with retinal degeneration. Lafaut et al4 reported a single patient who had bilateral Stargardt's disease and unilateral myopia.
Normally, axial elongation and ocular enlargement are carefully coordinated to equalise growth of fellow eyes in the quest for emmetropia.1 The differences observed in the two siblings described here reflect a decoupling of this developmental synchrony. It has been demonstrated that form deprivation in various species produces progressive axial growth and myopia of the postnatal eye.5 However, in both our sibs the ERG responses were much better preserved in the highly myopic right eye where, in addition, there was a low b:a ratio. Similar findings do not occur in myopia without retinal pathology.6
The bilateral symmetrical retinal dystrophy noted in both our patients suggests a genetic basis for the disease but a single genetic defect cannot explain the additional asymmetry of eye size and electrophysiological measurements. Most probably, the phenotype results from at least two separate events, a germline mutation in a retinal or retinal pigment epithelial specific gene leading to degeneration, thereby creating a susceptible background on which a second event could occur. This event, leading to the asymmetry of ocular volume, may be an environmental factor or a mutation in a second gene important in the regulation of eye growth. If this were a somatic rather than germline mutation it would explain the asymmetry of the disease.
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