Overlapping retinal phenotypes in a consanguineous family harboring mutations in CRB1 and RS1

To describe and distinguish overlapping retinal phenotypes in a consanguineous family harboring mutations in CRB1 and RS1, two different genes that are associated with splitting of the central neurosensory retina.

Retrospective case series.

Three siblings and their father had decreased vision from early childhood, but the father was unavailable for clinical examination. The proband, an 11-year old boy, had clinical features classic for CRB1-retinopathy (nummular pigmentary degeneration, relatively plump vessels, thickened retinal by optical coherence tomography with cystoid splitting in the central macula). The younger brother had right eye cataract with retinal detachment (presumed traumatic) and neurosensory retinal splitting in the central and peripheral retina with nummular pigmentary changes. It was assumed both brothers had the same disease until examination of the older sister, who had bilateral central and peripheral neurosensory retinal splitting in a pattern classic for X-linked retinoschisis and without any evidence for CRB1-retinopathy. The mother had an unremarkable clinical examination. ERG testing and directed genetic testing of CRB1 and RS1 for the family members confirmed CRB1-retinopathy in the proband, X-linked retinoschisis in the younger brother (hemizygous RS1 mutation), and X-linked retinoschisis in the older sister (homozygous RS1 mutation). The mother was confirmed as a carrier for both mutations.

A consanguineous family affected by retinal degenerative disease may have homozygous mutations in more than one gene, and this includes the possibility of homozygosity for X-linked disease. Electroretinography can be useful in distinguishing CRB1-retinopathy from X-linked retinoschisis.