Epidemiology, onset & clinical features


Based on data from Finland (where the highest prevalence has been reported, due to 3 founder mutations) and The Netherlands, the prevalence is estimated to be 1 in 15,000 to 1 in 30,000. XLRS has also been reported in Indonesian, Chinese, Japanese, Indian, and Portuguese families. The disease is primarily seen in males and is a leading cause of macular degeneration in male children. Rarely, women with pathogenic mutations on both alleles of the gene have been reported.


XLRS is diagnosed in the first decade of life, most frequently in school-age children but in some cases as early as age of 3 months.

Clinical features

Majority of patients presents at school age with decreased vision and reading difficulties. Some patients present early in infancy with squint and nystagmus. Variation in disease presentation, severity and progression is typical, and is observed even within the same family or among individuals who carry the same mutation in the causative gene.
Visual impairment is variable with best-corrected visual acuity from 20/20 to 20/600. Affected males typically have vision of 20/60 to 20/120. Visual acuity often deteriorates during the first and second decades of life. Then it remains relatively stable and very slowly progressing. Atrophic changes in the macula, usually symmetric and bilateral, are common in individuals over age 50 years. Visual loss may progress to legal blindness by the sixth or seventh decade.

The hallmark feature of the disease is foveal schisis (retinal splitting) though over time this may become less distinct. More than 50% of patients have some peripheral retinoschisis (mostly in the inferotemporal region) that can vary from shallow schisis to marked elevation in the inner leaflet over a large retinal area. Breaks occur within the inner layer varying from small holes to large tears. Vessels crossing between the walls of the schisis may be unsupported and at risk of hemorrhage. Additional peripheral changes may include pigmentation, which can resemble retinitis pigmentosa, sublinear retinal fibrosis, white retinal flecks and vascular attenuation or sheathing. Some patients present an inner retinal reflex resembling a tapetal reflex. XLRS may progress to retinal detachment in 5-22% of affected individuals, including infants with severe retinoschisis. Four to 40% of individuals with XLRS may develop vitreous hemorrhage.

Carrier females almost always have normal visual function and normal electroretinogram (ERG). Rarely, white flecks or areas of schisis in the peripheral retina can be present. So far, affected females have been reported only twice in the literature, one of these report describing females with XLRS from a highly consanguineous Columbian family.