First described in 1994 by Kaplan et al. [8], POH is thought to be caused by heterozygous inactivating mutations of the guanine nucleotide-binding protein, alpha-stimulating (GNAS) gene, which encodes the alpha subunit of the G-stimulatory protein of adenylyl cyclase (Gsα) [2,4,9]. Here, GNAS is linked to progressive osseous heteroplasia.