Mutations in HOXA13 and HOXD13 are associated with disorders of limb formation such as hand-foot-genital syndrome (HFGS), synpolydactyly (SPD), and brachydactyly.
Similar types of mutation (plus eight alanines) have recently been found in another HFGS family and also in the human HOXD13 gene (plus seven up to plus 14 residues) where it leads to synpolydactyly (SPD), a further congenital limb malformation rarely associated with genital abnormalities.
HOX genes play a fundamental role in the development of the vertebrate central nervous system, axial skeleton, limbs, gut, urogenital tract and external genitalia, but it is only in the last 4 years that mutations in two of the 39 human HOX genes have been shown to cause congenital malformations; HOXD13, which is mutated in synpolydactyly, and HOXA13, which is mutated in Hand-Foot-Genital syndrome.