Novel phenotypic and genotypic findings in X-linked retinoschisis

Objective: To describe atypical phenotypes associated with the retinoschisis (X-linked, juvenile) 1 mutation (RS1). Methods: Seven patients with multiple fine white dots at the macula and reduced visual acuity were evaluated. Six patients underwent pattern and full-field electroretinography (ERG). On-off ERG, optical coherence tomography, and fundus autofluorescence imaging were performed in some patients. Mutational screening of RS1 was prompted by the ERG findings. Results: Fine white dots resembling drusenlike deposits and sometimes associated with retinal pigment epithelial abnormalities were present in the maculae. An electronegative bright-flash ERG configuration was present in all patients tested, and abnormal pattern ERG findings confirmed macular dysfunction. A parafoveal ring of high-density autofluorescence was present in 3 eyes; 1 patient showed high-density foci concordant with the white dots. Optical coherence tomography did not show foveal schisis in 3 of 4 eyes. All patients carried mutations in RS1, including 1 with a novel 206T -> C mutation in exon 4. Conclusions: Multiple fine white dots at the macula may be the initial fundus feature in RS1 mutation. Electrophysiologic findings suggest dysfunction after photo-transduction and enable focused mutational screening. Auto fluorescence imaging results suggest early retinal pigment epithelium involvement; a parafoveal ring of high-density autofluorescence has not previously been described in this disorder.