SMAD4 and pachyonychia congenita: The occurrence of additional mutations in key tumor suppressor genes, including cyclin-dependent kinase inhibitor 2A (CDKN2A), SMAD family member 4 (SMAD4), has been linked to the disruption of the cell cycle and the eventual development of carcinogenesis in 46–60% of CDKN2A cases [35,36,37] and 31–38% of SMAD4 cases during the advanced stages of PC [36,38].