IRX5 and Craniofacial dysplasia-osteopenia syndrome: Irx3flox/flox/Irx5−/−/Osx-Cre+ mice that survive to 3–4 weeks of age have smaller femora and tibiae and appeared to have signs of bone fragility, which is consistent with reports of Hamamy syndrome patients developing bone fragility and long bone fractures later in life (Hamamy et al., 2007a).