Cutaneous features of SDR9C7 variants in eight subjects with autosomal recessive nonsyndromic epidermal differentiation disorders

Abstract

Epidermal differentiation disorders (EDD) are a heterogeneous group of disorders characterized by scaling and erythema. SDR9C7 encodes a short-chain dehydrogenase involved in epidermal differentiation and vitamin A metabolism, and pathogenic variants in this gene are a rare cause of nonsyndromic EDD (nEDD). To further delineate the clinical phenotype of SDR9C7-nEDD, we report eight individuals with SDR9C7 variants enrolled in the National Registry for Ichthyosis and Related Skin Disorders. Common features included fine scaling, hyperlinear palms, and greater severity on the extremities, especially the lower extremities. One subject showed plate-like scale and palmoplantar keratoderma, highlighting phenotypic diversity. Hypohidrosis, impaired thermoregulation, frequent dermatophyte skin and nail infections, and otologic findings were common, whereas ectropion and scalp involvement were absent. Topical emollients containing ammonium lactate or alpha-hydroxy acids improved scaling and dryness. Hydrocortisone reduced pruritus in some cases, and one severe case required systemic retinoids. These findings expand the clinical spectrum of SDR9C7-nEDD.