X-linked retinoschisis: an update

X-linked retinoschisis (XLRS) is a retinal dystrophy caused by mutations in the RS1 gene in Xp22.1, which leads to schisis (splitting) of the neural retina leading to reduced visual acuity in affected men (OMIM #312700). The condition accounts for almost all congenital retinoschisis with occasional reports of autosomal dominant retinoschisis making up the remainder. 1 The split in the retina occurs predominantly within the inner retinal layers and is very different from retinal detachment, which is a split between the neural retina and the retinal pigment epithelium. XLRS was first described in the 19th century 2 and documented as X linked in 1913.(3) Several cases were then described but were given alternative names including neuroretinal disease in men 4 and congenital vascular veils in the retina. 5 The term X linked retinoschisis'' was first used in 1953 6 and this, together with juvenile retinoschisis,'' 7 is now the generally accepted term. The causative gene RS1 was identified in 1997 8 and numerous inactivating mutations have since been found(9) (http://www.dmd.nl/rs/index.html). Investigation of the protein retinoschisin, encoded by RS1, has revealed it to be a secretory protein, containing a discoidin domain and functioning as an octamer.(10-13) Three retinoschisis mouse models have been developed and they have similar retinal pathology to the human disease.(14-16) This article aims to review the clinical, pathological and electrophysiological features of XLRS, our current understanding of its molecular basis and to consider future therapy.