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.