Phenotypic Variability in Genetically Defined X-linked Congenital Stationary Night Blindness

Abstract

Purpose: : Congenital stationary night blindness (CSNB) represents a group of non-progressive congenital retinal disorders that are characterized by abnormal ERGs, impaired night vision, a normal fundus, myopia, nystagmus, and strabismus. Two genetic forms of X-linked CSNB (CSNB1, mutant in the NYX gene; CSNB2, mutant in the CACNA1F gene) are known to present with clinically variable phenotypes. The aim of this study was to establish the degree of the phenotypic variability in a large set of CSNB patient.

Methods: : A retrospective review of a cohort of genetically defined CSNB patients (all males), including 147 cases from our CSNB study group and 56 reported from other centers, was performed. The clinical data included visual acuity (VA), ERG, refractive error (RE), complaints of night blindness, nystagmus, and strabismus.

Results: : Data from 149 CSNB2 patients with CACNA1F mutations and 54 CSNB1 patients with NYX mutations were analyzed. Every one of these 203 CSNB patients had abnormal ERGs with 100% of the CSNB1 patients and 69 % of the CSNB2 patients revealing a ‘negative’ bright flash (BF) scotopic ERG. All CSNB patients had abnormal VA (mean 0.33 log MAR / 20/40 Snellen), though the variability in VA was significantly greater among CSNB2 than among the CSNB1 patients (F = 2.68, p = 0.01). CSNB1 patients had RE varying from mild to severe myopia (mean -9.73D), while the CSNB2 patients had RE varying from moderate hypermetropia to severe myopia (mean -3.43D), although the degree of variability in RE between CSNB1 and CSNB2 was not significantly different (F = 1.15, p > 0.5). 95% of CSNB1 patients complained of impaired night vision compared to 45% of the CSNB2 patients. Nystagmus was present in 67% and 45% and strabismus in 11% and 34% of CSNB1 and CSNB2 patients, respectively.

Keywords: degenerations/dystrophies • genetics • retinal degenerations: hereditary