SMAD4 and pachyonychia congenita: For other tumor suppressor genes such as MAP2K4, MADH4 (SMAD4/DAC4), ACVR1B (ALK4, activin receptor type 1B) known to undergo germ-line or somatic genetic inactivation in clinically sporadic PC, no germ-line mutations could be identified in any of the FPC kindreds tested (76).