Previously unreported clinical features of PC include development of painful oral and nipple lesions during breastfeeding, copious production of waxy material in ears, and inability to walk without an ambulatory aid (50%). Stratification of these data by keratin mutation confirmed the increased incidence of cyst formation and natal teeth among PC-2 patients, although cysts were more commonly seen in PC-1 than previously reported (25%–33%). Prospective evaluation of 57 PC patients from 41 families revealed variable clinical findings: hyperhidrosis (79%), oral leukokeratosis (75%), follicular keratosis (65%), palmar keratoderma (60%), cutaneous cysts (35%), hoarseness or laryngeal involvement (16%), coarse or twisted hair (26%), early primary tooth loss (14%), and presence of natal or prenatal teeth (2%). Analysis of clinical, pathological, and genetic data from the literature and two research registries reveal that >97% of PC cases exhibit fingernail and toenail thickening, and painful plantar keratoderma. Pathogenic mutations in keratins K6a or K16 are associated with the PC-1 phenotype whereas K6b and K17 mutations are associated with the PC-2 phenotype. Pachyonychia congenita (PC) is a rare genodermatosis affecting the nails, skin, oral mucosae, larynx, hair, and teeth.
