IRX3 and Craniofacial dysplasia-osteopenia syndrome: Irx3−/− and Irx5−/− mice do not show any Hamamy syndrome characteristics (Costantini et al., 2005, Smemo et al., 2014), but several aspects of the Hamamy syndrome phenotype are recapitulated in Irx3 and Irx5 double knockout mice (Irx3−/−/Irx5−/− mice), including the cardiac defects and craniofacial dysmorphisms (Hiroi et al., 2001).