Focal Palmoplantar Keratoderma and Gingival Keratosis Caused by a KRT16 Mutation

To the Editor: Focal palmoplantar keratoderma and gingival keratosis (FPGK)(Online Mendelian Inheritance in Man [OMIM] 148730) is a rare autosomal-dominant syndrome featuring focal, pressure-related, painful palmoplantar keratoderma and gingival hyperkeratosis presenting as leukokeratosis.Focal palmoplantar keratoderma and gingival keratosis was first defined by Gorlin 1 in 1976.Since then, only a few cases have been reported, but no causative mutations have been identified. 2Focal pressure-related palmoplantar keratoderma (PPK) and oral hyperkeratosis also are seen in pachyonychia congenita (PC) (OMIM 167200, 615726, 615728, 167210), a rare autosomal-dominant disorder of keratinization characterized by PPK and nail dystrophy.Patients with PC often present with plantar pain; more variable features include oral leukokeratosis, follicular hyperkeratosis, pilosebaceous and epidermal inclusion cysts, hoarseness, hyperhidrosis, and natal teeth.Pachyonychia congenita is caused by mutation in keratin genes KRT6A, KRT6B, KRT16, or KRT17.Focal palmoplantar keratoderma and gingival keratosis as well as PC are distinct from other forms of PPK with gingival involvement such as Papillon-Lefèvre syndrome (OMIM 245000) and Olmsted syndrome (OMIM 614594).Papillon-Lefèvre syndrome is a rare autosomal-recessive disorder caused by mutations in the cathepsin C, CTSC, gene that exhibits erythematous, diffuse, transgradient PPK and early severe periodontitis.Olmsted syndrome is caused by autosomal-dominant gene mutations in transient receptor potential cation channel, subfamily V, member 3, TRPV3, and is characterized by severe bilateral transgradient PPK with leukoplakia of the tongue and buccal mucosa but also usually exhibits marked periorificial keratotic plaques, which facilitate exclusion of other phenotypically similar syndromes.