Furthermore, the hind limb skeletal hypoplasia reported in Irx3−/−/Irx5−/− mouse embryos and the femoral fragility observed in Hamamy syndrome patients suggest that IRX3 and IRX5 are important for limb development in vertebrates (Gaborit et al., 2012, Hamamy et al., 2007a). Here, IRX5 is linked to Craniofacial dysplasia-osteopenia syndrome.