GLI3-related polydactyly: a review

Clin Genet. 2017 Nov;92(5):457-466. doi: 10.1111/cge.12952. Epub 2017 Feb 22.


GLI3 mutations are known to be associated with nine syndromes/conditions in which polydactyly is a feature. In this review, the embryology, pathogenesis, and animal models of GLI3-related polydactyly are discussed first. This is followed by a detailed review of the genotype-phenotype correlations. Based on our review of the literature and our clinical experiences, we recommend viewing GLI3-related syndromes/conditions as four separate entities; each characterized by a specific pattern of polydactyly. These four entities are: the preaxial polydactyly type IV-Greig-acrocallosal spectrum, postaxial polydactyly types A/B, Pallister-Hall syndrome (PHS), and oral-facial-digital overlap syndrome. We also provide illustrative clinical examples from our practice including a family with a novel GLI3 mutation causing PHS. The review also introduces the term 'Forme Fruste' preaxial polydactyly and gives several conclusions/recommendations including the recommendation to revise the current criteria for the clinical diagnosis of PHS.

Keywords: GLI3; Greig cephalopolysyndactyly; Pallister-Hall; polydactyly.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Genetic Association Studies
  • Humans
  • Polydactyly / embryology
  • Polydactyly / genetics*
  • Syndrome
  • Zinc Finger Protein Gli3 / genetics*


  • Zinc Finger Protein Gli3