SG10 Features of paediatric pachyonychia congenita (KRT6A/6B/6C/16/17-pEDD)

Abstract

Pachyonychia congenita (PC) is a group of rare autosomal dominant genodermatoses caused by mutations in five keratin genes. It was recently reclassified by genotype as KRT6A-pEDD, KRT6B-pEDD, KRT6C-pEDD, KRT16-pEDD and KRT17-pEDD. While the classic triad of plantar pain, palmoplantar keratoderma and nail dystrophy is well documented in adults, phenotypic expression and genotype–phenotype correlations in paediatric populations remain less defined. The aim of this study was to identify the prevalence of PC-related features and ascertain genotype–phenotype correlations in children and young people (aged < 21 years). Data were extracted from the International Pachyonychia Congenita Research Registry. Inclusion criteria were age < 21 years and a confirmed pathogenic mutation in one of the five PC-related keratin genes. As of September 2024, 209 eligible individuals were identified (mean age 13.8 years; 50% male). The most frequent subtype was KRT6A-pEDD (53%), followed by KRT17-pEDD (23%), KRT16-pEDD (17%), KRT6B-pEDD (5%) and KRT6C-pEDD (2%). Significant genotype–phenotype correlations were observed. Patients with KRT16-pEDD had the highest frequency of calluses, blisters and thickened skin (74%), while those with KRT17-pEDD had the lowest (29%; P < 0.001). Patients with KRT6B-pEDD reported fewer nail abnormalities (P < 0.001). KRT17-pEDD was significantly associated with follicular hyperkeratosis (42%, P < 0.001), cysts (65%, P < 0.001), natal teeth (75%, P < 0.001) and premature tooth loss (19%, P = 0.003). No significant difference was found in the use of special shoes or mobility aids across groups. Although key features of PC typically manifest in early childhood, only 25% of patients receive a diagnosis by the age of 1 year. These findings highlight distinct paediatric phenotypic profiles based on genotype. Improving recognition of these early correlations may facilitate earlier diagnosis, timely genetic counselling and the implementation of subtype-specific management strategies.