Novel Clinical Manifestation of Congenital X-Linked Retinoschisis FREE

Traditionally, congenital X-linked retinoschisis (CXLRS) has been defined as a juvenile macular dystrophy.¹ It is characterized by foveal schisis accompanied by an abnormally reduced b-wave on electroretinography.² The gene for CXLRS, RS1, has been mapped to the short arm of the X chromosome and encodes for the protein retinoschisin.^3- 4 Schisis spaces, visible on optical coherence tomography (OCT), have been reported in the fovea in virtually all cases.⁵ We report a case of CXLRS followed up for 6 years with no evidence of foveal schisis on OCT and excellently maintained central vision.

The patient was referred to the Associated Retinal Consultants, Royal Oak, Michigan, in 2004 at age 9 years. At this time, he had a 2-year history of recurrent vitreous hemorrhages in the left eye with a recent spontaneous vitreous hemorrhage in the right eye. His visual acuity was 20/30 OU. Dilated fundus examination revealed bilateral nasal dragging of his discs, absent foveal reflexes, and bilateral peripheral schisis cavities (Figure 1). A diagnosis of probable CXLRS was given, and the patient was scheduled for electroretinography as well as an examination under anesthesia with OCT. His OCT findings confirmed the presence of bilateral peripheral schisis cavities, and electroretinography showed decreased a- and b-waves. A detailed family history revealed a maternal grandfather diagnosed as having retinitis pigmentosa, which likely represents a misdiagnosed case of CXLRS. Unfortunately, it was not possible to examine the patient's grandfather to confirm or disprove this theory. The patient was followed up at regular 6-month intervals with serial clinical examinations and OCT scans. Vision and funduscopic examination findings remained stable. In 2010, his peripheral blood was screened for mutations in RS1. This test showed a positive missense mutation, R102Q (CGG to CAG), on exon 4 of RS1. At his most recent follow-up visit in October 2010, his visual acuity was 20/25⁻¹ OD and 20/20⁺¹ OS. Spectral-domain OCT showed redemonstration of peripheral schisis cavities but failed to show any detectable evidence of the foveal cystic changes that have been considered universal in CXLRS (Figure 2). Central foveal thickness was normal at 266 μm OD and 276 μm OS. A return visit was scheduled for 6 months later.

We report a case with the classic diagnostic criteria for CXLRS: abnormal electroretinographic findings, clinically evident peripheral schisis cavities with associated visual field abnormalities, and confirmed mutation in RS1. The R102Q mutation in RS1 has previously been reported in clinically diagnosed cases of CXLRS.⁶ This case is unique in that the patient has failed to develop foveal involvement during the 6 years in which he has been closely followed up. The novel clinical manifestation of this case underscores the need for a formal genetic evaluation in any child with suspected genetically controlled retinal pathology. In the updated classification system for CXLRS inclusive of OCT findings, all 4 subtypes demonstrate foveal cystic schisis.^1- 2 Although this patient has multiple features of CXLRS, his lack of this critical finding places him outside this previously described classification system. It has been observed that children with CXLRS may not have clinical foveal changes at birth, but they usually manifest by age 8 years in our experience. The clinical picture of this case is somewhat of an outlier. This case may represent a fifth type of CXLRS with peripheral schisis and no associated macular lamellar schisis or foveal cystic schisis.