Phenotypic expression of juvenile X-linked retinoschisis in Swedish families with different mutations in the XLRS1 gene

Objective: To describe the clinical phenotype of juvenile X-linked retinosc hisis in patients with different mutations in the XLRS1 gene. Methods: Thirty patients with 7 different XLRS1 mutations were examined. Th e genotype was determined by molecular genetics, which identified 6 known a nd 1 novel mutation (exon 5, 489 G-->T). Ophthalmologic examination include d full-field electroretinogram (ERG) recordings. Results: The fundus appearance showed marked variations between, as well as within, families with different XLRS1 mutations. The ERG demonstrated typi cal reduction of B-wave amplitude, with relative A-wave preservation, causi ng a reduced B-A ratio in all affected males. The implicit time of the 30-H z flicker ERG was prolonged in all patients examined. In a large family wit h a deletion of exon 1 and the promoter region, 12 affected males showed a phenotype ranging from moderate to severe vision impairment and a broad ran ge of ERG abnormality, suggesting that additional factors may contribute to the disease severity. Conclusions: Juvenile retinoschisis shows a wide variability in the phenoty pe between, as well as within, families with different genotypes. The ERG f indings show reduced B-A ratios of dark-adapted recordings and prolonged im plicit times of 30-Hz flicker response, which provide a useful clinical mar ker to confirm the clinical diagnosis. Clinical Relevance: This study describes the wide variability in the phenot ype in patients with juvenile retinoschisis and different mutations in the, XLRS1 gene. The study emphasizes the importance of complementing the ophtha lmologic examination with full-field ERG and molecular genetics in boys wit h visual failure of unknown etiology to determine the diagnosis early in th e course of the disease.