Cutaneous features of SDR9C7 mutation in seven patients with autosomal recessive congenital ichthyosis

Summary: Abstract Body: Ichthyoses are a heterogeneous group of skin disorders characterized by scaling and erythema. SDR9C7 has been recently recognized as a cause of autosomal recessive congenital ichthyosis (ARCI). Due to the rarity of SDR9C7 mutations in ARCI, there is limited information regarding the associated cutaneous manifestations, comorbidities, and available treatments. We present seven cases of SDR9C7 mutations, detailing their clinical characteristics and management. The genotypes and clinical characteristics of the seven individuals were obtained from the National Registry for Ichthyosis. Among our seven cases, we observe that these individuals exhibited a vulgaris-like phenotype, with fine, white scaling and hyperlinear palms. Notably, common features of ichthyosis, such as ectropion and palmoplantar keratoderma, were absent in this cohort. However, other characteristic features, including hypohidrosis, impaired thermoregulation, and recurrent skin infections, were frequently reported. Topical emollients, particularly those containing ammonium lactate and alpha-hydroxy acids, proved effective in reducing scale, dryness, and pruritus. Regular baths also helped remove scale. Similar to other ichthyoses, the lower extremities demonstrated the most prominent scaling. Recently, SDR9C7 has been identified as a crucial regulator of epidermal barrier function, specifically by facilitating the covalent bonding of ceramides and the formation of the corneocyte lipid envelope. These findings help explain the characteristic clinical features of ARCI in individuals with SDR9C7 mutations, including dry skin, scaling, and hyperkeratosis. Furthermore, SDR9C7’s role in vitamin A metabolism – which is essential for epidermal differentiation – underscores the therapeutic efficacy of vitamin A derivatives in treating ichthyosis. This connection also suggests that retinoids could be an effective treatment option for the SDR9C7 subgroup of ARCI patients. Caroline Echeandia-Francis¹, Dawn H. Siegel², Amy Paller³, Keith Choate¹ 1. Yale University School of Medicine, New Haven, CT, United States. 2. Stanford University School of Medicine, Stanford, CA, United States. 3. Northwestern University Feinberg School of Medicine, Chicago, IL, United States. Genetic Disease, Gene Regulation, Gene Therapy & Epigenetics