The role of GLI genes in development was first revealed by the discovery of deleterious variants in GLI3 in several human congenital malformations, including Pallister–Hall syndrome (PHS) (Kang et al., 1997), Greig cephalopolysyndactyly syndrome (GCPS) (Vortkamp et al., 1991), non-syndromic polydactyly (Radhakrishna et al., 1999), and acrocallosal syndrome (Elson et al., 2002). This evidence concerns the gene GLI3 and Greig cephalopolysyndactyly syndrome.