Both gain- or loss-of-function mutations in GNAS have been found to cause severe cranial bone defects in MAS or POH human patients, respectively.8,9 Our findings in this study support a model in which normal intramembranous bone development shares common underlying cellular and molecular mechanisms with ectopic intramembranous bone formation such as the one in POH. This evidence concerns the gene GNAS and progressive osseous heteroplasia.