Atypical Fundus Findings in X–Linked Retinoschisis

Abstract

 

Purpose:

 

X–linked retinoschisis (XLRS; OMIM # 312700) is an X–linked inherited retinal disorder, which can usually be diagnosed with a careful fundus examination. The aim of this study is to present patients with XLRS in whom the fundus findings are insufficient to establish the diagnosis of XLRS, and to suggest an approach to reach the correct diagnosis.

 

Methods:

 

To date, a series of 38 male patients who have been conclusively given the diagnosis of XLRS have been evaluated in this study. A full ophthalmological examination included a dilated fundus exam and optical coherence tomography (OCT) of the macular area. Visual function measurements included best–corrected visual acuity, Goldmann kinetic perimetry, and electroretinography (ISCEV standard full–field ERG). Their DNA was extracted from a blood sample and screened for mutations in the XLRS1 gene by sequencing all six exons of this gene.

 

Results:

 

As expected, most patients (32/38) had fundus findings compatible with the diagnosis of XLRS, such as cystoid schisis spaces in the macular area and/or elevated or flat retinoschisis in the peripheral retina. In six patients (see table), fundus findings were non–specific. All showed atrophic changes and RPE pigmentation abnormalities in the macular area, but no macular schisis could be identified with either biomicroscopy or OCT. No peripheral schisis was seen. In all patients, a reduced (< 1.21) b–wave/a–wave amplitude ratio was detected in the combined ERG response ("electronegative" ERG). The diagnosis of XLRS was confirmed by detecting mutations in the XLRS1 gene predicted to be pathogenic.  

 

Conclusions:

 

In a significant minority of patients with XLRS, fundus findings were atypical. All of them were adults who showed macular atrophic changes; some of them carried the diagnosis of macular dystrophy. In view of these findings, XLRS should be included in the differential diagnosis of a male patient with an atrophic maculopathy of unknown etiology. An electronegative ERG argues in favor of this diagnosis, which can be confirmed with XLRS1 mutation analysis.

 

Keywords: retinal degenerations: hereditary • mutations • electroretinography: clinical