Early-onset severe rod-cone dystrophy in young children with RPE65 mutations

PURPOSE. To describe the ocular phenotype of patients with RPE65 mutations in infancy and young childhood. METHODS. Four children from three families with severe early-onset visual i mpairment related to electrophysiologically detectable retinal dystrophy we re screened for mutations in the RPE65 gene. Visual function from infancy t o the age of 10 years was assessed with age-adapted methods. Clinical exami nations and electroretinograms (ERGs) were also performed on the six parent s. RESULTS. in all three families, patients were compound heterozygous for mut ations of the RPE65 gene (ins144T/IVS1 + 5G-->A, R91W/Y368H, 1114delA + T45 7N/IVS1 + 5G-->A). Visual acuity was measurable in all patients at the age of 6 to 10 years, despite severe visual impairment noted during infancy and congenital nystagmus in three of the four patients. Photophobia was not a feature. Funduscopic changes were discrete, the most prominent finding bein g increased granularity in the macula and the periphery. Peripheral vision was well preserved, measured by Goldmann perimetry. Rod ERGs were not recor dable, whereas cone ERGs were detectable in early childhood. All features t aken together suggest a specific form of Leber congenital amaurosis (LCA) d istinguishable on clinical grounds. ERGs were normal in five of the six par ents. One father had an ERG compatible with congenital stationary night bli ndness unrelated to his hc heterozygous state for the RPE65 mutation. CONCLUSIONS. RPE65 mutations on both alleles may be associated with early-o nset severe rod-cone dystrophy. Visual functions of the four patients were better than is usually seen in LCA, in particular in cases associated with retGC1 mutations. RPE65 mutations should be suspected in infants who appear to be blind in dim surroundings but react to objects in bright illuminatio n and have nonrecordable rod ERGs and residual cone ERGs.