Pachyonychia congenita is caused by mutations in genes that encode keratins, proteins that are the main structural components of skin, nails, and hair. The mutations prevent keratins from forming the strong network of filaments that normally gives skin cells strength and resilience. As a result, even normal activities like walking can cause cells to break down, ultimately leading to the painful blisters and calluses that are the most debilitating features of the disorder.