A Novel Mutation in the HPGD Gene Results in the Unusual Phenotype of: Palmoplantar Keratoderma with Digital Clubbing and Hyperhidrosis

A 24-year-old man presented to our clinic with a 10-year history of palmoplantar keratoderma (PPK), hyperhidrosis and digital clubbing resistant to various treatments. Family history was negative for a similar condition. Whole exome sequencing was performed on the patients' DNA and revealed a novel missense mutation, designated p.His156Gln, in the HPGD gene. PPKs may be inherited or acquired, however the triad of PPK, hyperhidrosis and digital clubbing has not been previously reported. HPGD has been previously described in the pathogenesis of hypertrophic osteoarthropathy as well as hyperhidrosis, however its role in palmoplantar keratoderma has not been evaluated. Here we identify a novel mutation implicated in the pathogenesis of this condition. Palmoplantar keratoderma (PPK) is a disorder of keratinization. Here, we present an unusual case of PPK in association with hyperhidrosis and digital clubbing. To the best of our knowledge these associations have not been previously reported.