APAF1 and familial clubfoot with or without associated lower limb anomalies: Further investigation explored an additional five genes linked to apoptosis mediated by mitochondria, namely, CASP9, CASP3, apoptotic protease-activating factor 1 (APAF1), B cell lymphoma 2 (BCL2), and BH3-interacting domain death agonist (BID), revealing possible associations between genetic mutations in these genes and the occurrence of clubfoot.55, 56, 57 The deletion region of 2q31-33 encompasses the cluster of homeobox D genes (HOXD), which plays a crucial role in directing limb and muscle patterning during embryonic development.