Since the global loss of both Irx3 and Irx5 leads to cardiac phenotypes similar to those seen in Hamamy patients, we wanted to see if the decreased mineralization we found in Irx3flox/flox/Irx5−/−/Osx-Cre+ mice also reflected the clinical presentation of Hamamy syndrome patients. Here, IRX5 is linked to Craniofacial dysplasia-osteopenia syndrome.