Disparate X-linked retinoschisis phenotypes in fraternal twins with the same pathogenic variant in the RS1 gene

In X-linked retinoschisis (XLRS), the RS1 pathogenic variant and the patient's age might be the most important determinants of the XLRS phenotype. In this case report, we present fraternal twins with the same RS1 pathogenic mutation who were examined at the same age yet exhibited significantly different phenotypes.

This is a retrospective case report. Both patients underwent best-corrected visual acuity (BCVA) testing, slit-lamp examination, wide-field fundus imaging, optical coherence tomography (OCT), and genetic testing on the same day.

Fraternal twins, aged 21, were found to be hemizygous for the c.267T>A p. (Tyr89*) mutation in the RS1 gene. The first patient presented with a spoke-wheel pattern in the macula, extensive intraretinal cystoid cavities (ICC), and peripheral retinoschisis inferiorly and temporally, accompanied by breaks in the inner retinal layers. The second patient exhibited only tiny ICCs in the macula with mild disruption of the ellipsoid zone at the fovea and no peripheral retinoschisis.

Family members with the same pathogenic variant and of the same age can present with significantly different XLRS phenotypes. This highlights the importance of other factors, such as genetic modifiers, epigenetic regulatory events, and environmental influences, in contributing to phenotypic heterogeneity in XLRS patients.