Idiopathic talipes equinovarus (ITEV), more commonly known as clubfoot, is a developmental deformity characterized by rigid ankle equinus, hindfoot varus, and forefoot adduction. This common birth defect is treatable, but the etiology of ITEV is largely unknown. Recently, a deletion in the chromosomal region 2q31-33 was found to be associated with clubfoot. Microsatellite markers spanning the region were genotyped in 57 multiplex ITEV families and 83 simplex trios. Family-based analysis revealed that two microsatellite markers, GATA149B10 and D2S1371, were associated with ITEV in the simplex trios. The 6cM region between the two markers contained the candidate genes CASP8, CASP10, and CFLAR. These genes encode proteins that are regulators of apoptosis, which is important during growth and development. Genotyping of SNPs throughout the genes in this sample of ITEV families has revealed positive linkage with association to the major allele of a variant in CASP10 in simplex ITEV white and Hispanic trios. This study is the first to find evidence for a candidate gene for ITEV and provides a scientific foundation to further explore the contributions of other apoptotic genes in the etiology of clubfoot.