Advances in the molecular genetics of non-syndromic polydactyly

Abstract

Polydactyly is one of the most common inherited limb abnormalities, characterised by supernumerary fingers or toes. It results from disturbances in the normal programme of the anterior–posterior axis of the developing limb, with diverse aetiology and variable inter- and intra-familial clinical features. Polydactyly can occur as an isolated disorder (non-syndromic polydactyly) or as a part of an anomaly syndrome (syndromic polydactyly). On the basis of the anatomic location of the duplicated digits, non-syndromic polydactyly is divided into three kinds, including preaxial polydactyly, axial polydactyly and postaxial polydactyly. Non-syndromic polydactyly frequently exhibits an autosomal dominant inheritance with variable penetrance. To date, in human, at least ten loci and four disease-causing genes, including the GLI3 gene, the ZNF141 gene, the MIPOL1 gene and the PITX1 gene, have been identified. In this paper, we review clinical features of non-syndromic polydactyly and summarise the recent progress in the molecular genetics, including loci and genes that are responsible for the disorder, the signalling pathways that these genetic factors are involved in, as well as animal models of the disorder. These progresses will improve our understanding of the complex disorder and have implications on genetic counselling such as prenatal diagnosis.