Clinical presentations of X-linked retinoschisis in Taiwanese patients confirmed with genetic sequencing

PURPOSE To investigate the clinical characteristics of X-linked retinoschisis (XLRS) and identify genetic mutations in Taiwanese patients with XLRS. METHODS This study included 23 affected males from 16 families with XLRS. Fundus photography, spectral domain optical coherent tomography (SD-OCT), fundus autofluorescence (FAF), and full-field electroretinograms (ERGs) were performed. The coding regions of the RS1 gene that encodes retinoschisin were sequenced. RESULTS The median age at diagnosis was 18 years (range 4-58 years). The best-corrected visual acuity ranged from no light perception to 20/25. The typical spoke-wheel pattern in the macula was present in 61% of the patients (14/23) while peripheral retinoschisis was present in 43% of the patients (10/23). Four eyes presented with vitreous hemorrhage, and two eyes presented with leukocoria that mimics Coats' disease. Macular schisis was identified with SD-OCT in 82% of the eyes (31/38) while foveal atrophy was present in 18% of the eyes (7/38). Concentric area of high intensity was the most common FAF abnormality observed. Seven out of 12 patients (58%) showed electronegative ERG findings. Sequencing of the RS1 gene identified nine mutations, six of which were novel. The mutations are all located in exons 4-6, including six missense mutations, two nonsense mutations, and one deletion-caused frameshift mutation. CONCLUSIONS XLRS is a clinically heterogeneous disease with profound phenotypic inter- and intrafamiliar variability. Genetic sequencing is valuable as it allows a definite diagnosis of XLRS to be made without the classical clinical features and ERG findings. This study showed the variety of clinical features of XLRS and reported novel mutations.