To describe the clinical phenotype of juvenile X-linked retinoschisis in patients with different mutations in the XLRS1 gene. Methods: Thirty patients with 7 different XLRS1 mutations were examined. The genotype was determined by molecular genetics, which identified 6 known and 1 novel mutation (exon 5, 489 G→T). Ophthalmologic examination included 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 typical reduction of B-wave amplitude, with relative A-wave preservation, causing a reduced B-A ratio in all affected males. The implicit time of the 30-Hz flicker ERG was prolonged in all patients examined. In a large family with 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 range of ERG abnormality , suggesting that additional factors may contribute to the disease severity. Conclusions: Juvenile retinoschisis shows a wide variability in the phenotype between, as well as within, families with different genotypes. The ERG findings show reduced B-A ratios of dark-adapted recordings and prolonged implicit times of 30-Hz flicker response, which provide a useful clinical marker to confirm the clinical diagnosis. Clinical Relevance: This study describes the wide variability in the phenotype in patients with juvenile retinoschisis and different mutations in the XLRS1 gene. The study emphasizes the importance of complementing the ophthalmologic examination with full-field ERG and molecular genetics in boys with visual failure of unknown etiology to determine the diagnosis early in the course of the disease.

opmental glaucoma by monosomy 9p23 with trisomy 8q22. 2 The investigators attributed the responsible area of glaucoma to 8q22, not 9p23, because GLC1D maps to 8q22. That case also showed retained testis and hydronephrosis, similar to our patient. Interestingly, 2 previously reported cases 3,4 of monosomy 9p24-pter (near the 9p23 locus) manifested developmental glaucoma. Therefore, partial monosomy 9p might be causative for developmental glaucoma. Chromosome 13 seems essential for development of the eye. Trisomy 13 often results in severe ocular defects, including developmental glaucoma. 5 One case of developmental glaucoma and polydactyly with trisomy 13 was reported, 5 which is compatible with our case. In a French family with congenital microcoria, axial myopia, and juvenile open-angle glaucoma, genetic linkage to 13q31-32 was suggested to result in these ocular findings. 6 Although our patient had a normal pupil phenotype, trisomy 13q31 might be responsible for the developmental anomaly of angle. Taken together, it is suggested that the abnormalities of chromosome 9p23 and/or 13q31 are associated with developmental glaucoma with other systemic anomalies.

Patients with RM and mutations in the CNGA3/CNGB3 genes presented a similar clinical phenotype, confirming the essential function of both the alpha- and beta-subunits of the cGMP-gated cation channel in cone photoreceptor function. Small remaining cone responses in a few of the younger patients and mid-peripheral pigmentary degenerations in the oldest patient examined indicate that there could be some degree of progression in retinal dysfunction in at least some patients with RM.

Patients with BMD and mutations in the bestrophin gene have a similar clinical phenotype characterized by a variable, but relatively moderate visual acuity reduction, atrophic changes in the macula, and pathological results of the electro-oculograms. The macular appearance remains essentially unchanged through the atrophic stage (stage IV) in the majority of patients, indicating a stationary disease course associated with this specific genotype.

Four young males with XLRS did not present with reduction in the scotopic b-wave amplitude on full-field ERG, which is otherwise often considered to be characteristic of the disease. Full-field ERG and molecular genetic analysis of the RS1 gene still remain the most important diagnostic tools for this retinal disorder, although the OCT can be a valuable complement in order to make the diagnosis at an early stage.