Clinical and para-clinical description of a novel mutation for Schnyder dystrophy in a French family

Summary Introduction The objective of this article is to describe the evolution of Schnyder dystrophy in 3 related patients of different ages and to highlight the discovery of a new mutation unidentified until now. Case report We present a series of 3 cases, all first-degree relatives with no suggestion of consanguinity , of different ages (30, 40 and 59 years) and two distinct generations (mother and children). Slit lamp examination revealed the same lesions in our three patients: an early-onset corneal arcus senilis , central corneal deposits, and a gray stromal haze in the two oldest subjects. The older the patient, the more numerous and dense were these lesions. The various anterior segment OCTs showed an increase in the number of hyperreflective opacities in the anterior stroma and, in the older subject, the appearance of many posterior shadows. Monitoring of pachymetry by Pentacam ® showed progressive age-related thickening. All three patients had dyslipidemia treated with statins or diet alone. In our case we proposed treatment only to subject A because of the significant impact on her visual acuity . Discussion Numerous clinical, para-clinical and genetic descriptions of this disease are found in the literature. Schnyder dystrophy is rare but not unheard of and may be discovered fortuitously or in the setting of decreased visual acuity. Genetic analysis of our family revealed a mutation of the UBIAD1 gene not described in the literature. UBIAD1 encodes the protein domain-containing UbiA prenyltransferase 1 which converts vitamin K1 into K2 and is involved in the cholesterol synthesis pathway. In the case of a mutation, it is no longer functional, leading to the accumulation of cholesterol crystals. Given the clinical context and the presence of this variant of the reference sequence in all relatives, its pathogenesis is strongly suspected in our family. The originality of our article is to present the progression of the same pathology in 3 patients with the same mutation at different ages and degrees of severity. This notion of progressive worsening and the need to treat late in the majority of cases are found in literature. Conclusion The discovery of a new variant within the UBAID1 gene suggests its pathogenesis in view of the clinical features available to us. The dystrophy is initially asymptomatic before the high number of deposits becomes disabling.