087 Revisiting pachyonychia congenita: a case cohort study in 815 patients

Abstract

Pachyonychia congenita (PC) is a group of autosomal dominant disorders caused by mutations in one of 5 keratin genes (KRT6A, KRT6B, KRT6C, KRT16, or KRT17). The establishment of an international registry containing both clinical and molecular data led to the development of a disease classification based on the mutant gene and associated features. Here we harnessed the same resource to clarify the prevalence of PC-associated clinical features, delineate phenotype-genotype correlations and identify prognostic features for disease severity. 815 individuals with confirmed keratin mutations registered in the International Pachyonychia Congenita Research Registry (IPCRR) were surveyed for clinical findings associated with PC. Data were analyzed using Student T-test, Chi-Square, ANOVA tests (for differences in means/proportions), Spearman correlation and logistic regression (for phenotype-genotype correlation). KRT6A mutations were most common and evident in 40% of cases. Plantar keratoderma and toenail dystrophy were the most common clinical findings, with plantar keratoderma most significantly affecting patient’s quality of life. KRT6A mutations were associated with young age of onset, high number of fingernails/toenails involvement, oral leukokeratosis and hoarseness. Cysts and natal teeth were most common among patients carrying KRT17 mutations. Logistic regression models revealed that oral leukokeratosis correlated with earlier toenail involvement, walking aids use, nursing difficulties and hoarseness. Natal teeth and oral leukokeratosis were inversely correlated one relative to the other, while natal teeth and cysts positively correlated one with the other. Hoarseness predicted an increased number of involved fingernails. Our study reveals novel and clinically useful prognostic predictors in PC, and more generally demonstrates the importance of large registry-based careful studies in rare disorders.