Keratin 17-Related Recessive Atypical Pachyonychia Congenita with Variable Hair and Tooth Anomalies

This document reports the first known case of pachyonychia congenita (PC) affecting all ectodermal derivatives and the first recessive KRT17-related PC, observed in seven members across two consanguineous Pakistani families. The atypical PC is marked by a combination of symptoms including pachyonychia, plantar keratoderma, folliculitis, alopecia, sparse eyebrows, dental anomalies, and variable acanthosis nigricans, among others. Exome sequencing revealed a homozygous KRT17 c.281G>A (p.(Arg94His)) mutation in affected individuals, with linkage mapping supporting a single locus for the disorder. This contrasts with the heterozygous variants of KRT17, which cause PC2 with dominant inheritance and different symptoms. The study also highlights the importance of comprehensive genetic testing, as Sanger sequencing alone showed heterozygosity for the causal variant, suggesting that testing parents for variants found in siblings could reveal recessive inheritance patterns in other KRT genes as well.