Autosomal Recessive Palmoplantar Epidermal Differentiation Disorder Caused by Homozygous Stop-Gain Variant in KRT16 Gene

Palmoplantar epidermal differentiation disorders (pEDDs) comprise a heterogeneous group of disorders characterized by hyperkeratotic thickening of the palms and soles due to pathogenic variants in genes that regulate palmoplantar epidermal differentiation and keratinization. Among these, KRT16-pEDD is caused by heterozygous mutations in the KRT16 gene and may present clinically either as isolated palmoplantar keratoderma (PPK) or as part of the broader phenotype of pachyonychia congenita. This report describes a rare bi-allelic pattern of inheritance involving a presumed loss-of-function variant in KRT16, thereby extending the clinical and genetic spectrum of KRT16-related disorders, and highlighting important implications for variant interpretation and genetic counseling.