Although the Irx3−/−/Irx5−/− mice have a complete loss of protein in comparison to the point mutations found in humans with Hamamy syndrome, the finding that multiple features of Hamamy syndrome phenotype are recapitulated in Irx3−/−/Irx5−/− mice indicates that this mouse model may be useful for understanding the role of Iroquois proteins in vivo. Here, IRX3 is linked to Craniofacial dysplasia-osteopenia syndrome.