Polydactyly: phenotypes, genetics and classification

Clin Genet. 2014 Mar;85(3):203-12. doi: 10.1111/cge.12276. Epub 2013 Oct 18.


Polydactyly is one of the most common hereditary limb malformations featuring additional digits in hands and/or feet. It constituted the highest proportion among the congenital limb defects in various epidemiological surveys. Polydactyly, primarily presenting as an additional pre-axial or post-axial digit of autopod, is a highly heterogeneous condition and depicts broad inter- and intra-familial clinical variability. There is a plethora of polydactyly classification methods reported in the medical literature which approach the heterogeneity in polydactyly in various ways. In this communication, well-characterized, non-syndromic polydactylies in humans are reviewed. The cardinal features, phenotypic variability and molecular advances of each type have been presented. Polydactyly at cellular and developmental levels is mainly a failure in the control of digit number. Interestingly, GLI3 and SHH (ZRS/SHH enhancer), two antagonistic factors known to modulate digit number and identity during development, have also been implicated in polydactyly. Mutations in GLI3 and ZRS/SHH cause overlapping polydactyly phenotypes highlighting shared molecular cascades in the etiology of additional digits, and thus suggesting the lumping of at least six distinct polydactyly entities. However, owing to the extreme phenotypic and clinical heterogeneity witnessed in polydactyly a substantial genetic heterogeneity is expected across different populations and ethnic groups.

Keywords: additional digits; classification; clinical variability; genetic heterogeneity; polydactyly.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Enhancer Elements, Genetic
  • Genetic Association Studies
  • Genome-Wide Association Study
  • Hedgehog Proteins / genetics
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Nerve Tissue Proteins / genetics
  • Phenotype*
  • Polydactyly / classification
  • Polydactyly / diagnosis*
  • Polydactyly / genetics*
  • Syndactyly / diagnosis
  • Syndactyly / genetics
  • Zinc Finger Protein Gli3


  • GLI3 protein, human
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • Nerve Tissue Proteins
  • Zinc Finger Protein Gli3