Pattern dystrophy: evidence of digenic inheritance and studies of visual outcome

Abstract

Abstract: : Purpose: Pattern dystrophy is a dominantly inherited macula disease caused predominantly by mutations in the peripherin/RDS gene. The purpose of this study was to document the clinical progression of the maculopathy and perform genetic analyses on several large families with the condition. Methods: Six families (including 39 affected) were ascertained, clinically evaluated and genome–wide genotyping undertaken. Mutation detection by direct sequencing of the peripherin/RDS gene was performed. Results: The condition appears to be characterized clinically by the accumulation of yellow subretinal flecks following which pigmentation and overlying patches of chorioretinal atrophy appear. Subsequently, 50% of individuals with pattern dystrophy in our study, all over the age of 50 years, developed significant central visual impairment owing to the development of geographic atrophy or sub–retinal neovascularisation. The risk of these complications increases with age. All six families had mutations in the peripherin/RDS gene. In two pedigrees, each with a different missense mutation, disease development appeared dependent on linkage to a novel locus on another autosome, consistent with digenic inheritance. Conclusions: Pattern dystrophy is not a visually benign condition. Instead, patients should be counseled that there is a significant chance that central visual loss will be lost in later years. This is one of only a few human diseases to show evidence of digenic inheritance.

Keywords: retinal degenerations: hereditary • gene mapping • macula/fovea