Familial craniofacial fibrous dysplasia: absence of linkage to GNAS1 and the gene for cherubism.

Editor—Fibrous dysplasia is a benign fibro-osseous condition that may involve one or more bones in the cranial and extracranial skeleton. There are four main types of fibrous dysplasia: monostotic in which only one bone is affected1; polyostotic in which multiple bones are affected2; McCune-Albright syndrome (MIM 174800), a polyostotic form accompanied by pigmentation lesions and endocrine dysfunction presenting as precocious puberty in females3 4; and a craniofacial form (CFD) in which only bones of the craniofacial complex are affected.5 The majority of patients with CFD present in their second decade; the lesions are generally unilateral and tend to become static once skeletal maturity is reached.6 Fibrous dysplasia usually occurs with no family history, although CFD has been shown to be inherited in an autosomal dominant fashion.7 8 Activating mutations within the guanine nucleotide binding protein gene ( GNAS1 ) (MIM 139320), located on chromosome 20q13.2-13.3,9 have been identified in lesions from monostotic fibrous dysplasia,10polyostotic fibrous dysplasia,11 12 and McCune-Albright syndrome.13 At present it is unknown whether this gene is mutated in the germline of patients with familial CFD. Another candidate gene for …