Case Report: Successful topical simvastatin therapy in a 2-year-old girl with keratin 16-associated palmoplantar epidermal differentiation disorder.

Palmoplantar epidermal differentiation disorder associated with pachyonychia congenita is a rare autosomal dominant genodermatosis characterized by painful palmoplantar hyperkeratosis and nail dystrophy. Treatment options remain limited, particularly in young children, in whom systemic therapies carry safety concerns. Herein, we report a 2-year-old girl who presented with palmoplantar hyperkeratosis since 1 month of age, with progressive nail dystrophy involving all 20 nails. Whole-exome sequencing identified a hemizygous multi-exon deletion in keratin 16 (ClinVar: SUB16259296; OMIM: #167200), and orthogonal validation using amplicon-based high-throughput sequencing confirmed a 437-nucleotide deletion predicted to result in a frameshift with premature termination codon (PTC). American College of Medical Genetics and Genomics classification supported likely pathogenicity. Twice-daily application of topical 2.5% simvastatin/cholesterol cream for 11 weeks produced substantial improvement in plantar hyperkeratosis, resolution of painful fissures, and visibly improved morphology of nascent nail growth. No local or systemic adverse effects were observed. This case provides preliminary evidence that topical simvastatin may be an effective and well-tolerated therapy for keratin 16-associated palmoplantar epidermal differentiation disorder in young children, and highlights the potential importance of topical drug delivery in achieving therapeutic efficacy for this genetic subtype.