The molecular basis, involving mutations in six key genes (ARHGAP31, RBPJ, NOTCH1, DLL4, DOCK6, and EOGT) that disrupt critical cellular pathways including Notch signaling and Cdc42/Rac1-mediated cytoskeletal regulation, explains the wide phenotypic variability, from aplasia cutis congenita and limb defects to severe cardiovascular and neurological anomalies. The gene discussed is DOCK6; the disease is aplasia cutis congenita.