Polyostotic Fibrous Dysplasia Wikipedia

Description: McCune-Albright syndrome (polyostotic fibrous dysplasia), described in 1937 by Donovan James McCune and Fuller Albright, is a genetic disorder of bones, skin pigmentation and hormonal problems along with premature puberty. It is suspected when two of the three following features are present: (autonomous) endocrine hyperfunction such as precocious puberty Fibrous dysplasia Café-au-lait spots Within the syndrome there are bone fractures and deformity of the legs, arms and skull, different pigment patches on the skin, and early puberty with increased rate of growth. Polyostotic fibrous dysplasia has different levels of severity. For example one child may be entirely healthy with no outward evidence of bone or endocrine problems, enter puberty at close to the normal age and have no unusual skin pimgentation. The complete opposite of that would be children who are diagnosed in early infancy with the obvious bone disease and obvious increased endocrine secretions from several glands. Approximately 20-30% of fibrous dysplasias are polyostotic and two thirds of patients are polyostotic before the age of ten. Polyostotic fibrous dysplasia is usually caused by mosaicism for a mutation in a gene called GNAS1 (Guanine Nucleotide binding protein, Alpha Stimulating activity polypeptide 1). The syndrome shows a broad spectrum of severity. The disease frequently involves the skull and facial bones, pelvis, spine and shoulder girdle. The sites of involvement are the femur (91%), tibia (81%), pelvis (78%), ribs, skull and facial bones (50%), upper extremities, lumbar spine, clavicle, and cervical spine, in decreasing order of frequency. The craniofacial pattern of the disease occurs in 50% of patients with the polyostotic form of fibrous dysplasia. Genetically, there is a post-zygotic mutation of the gene GNAS1 which is involved in G-protein signalling. This mutation, often a mosaicism, prevents downregulation of cAMP signalling.