title: Severe endocrine and nonendocrine manifestations of the McCune-Albright syndrome associated with activating mutations of stimulatory G protein GS.
abstract: McCune-Albright syndrome (MCAS) is a sporadic disease classically including polyostotic fibrous dysplasia, café au lait spots, sexual precocity, and other hyperfunctional endocrinopathies. An activating missense mutation in the gene for the alpha subunit of GS, the G protein that stimulates cyclic adenosine monophosphate formation, has been reported to be present in these patients. The mutation is found in variable abundance in different affected endocrine and nonendocrine tissues, consistent with the mosaic distribution of abnormal cells generated by a somatic cell mutation early in embryogenesis. We describe three patients with MCAS who had profound endocrine and nonendocrine disease and who died in childhood. Two of the patients were severely ill neonates whose complex symptoms did not immediately suggest MCAS. A mutation of residue Arg201 of GS alpha was found in affected tissues from all three children. A review of the literature and unpublished case histories emphasizes the existence of other patients with severe and unusual clinical manifestations. We conclude that the manifestations of MCAS are more extensive than is generally appreciated, and may include hepatobiliary disease, cardiac disease, other nonendocrine abnormalities, and sudden or premature death.
authors.affiliation: Molecular Pathophysiology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: A
authors.initials: A
authors.lastname: Shenker
authors.forename: L S
authors.initials: LS
authors.lastname: Weinstein
authors.forename: A
authors.initials: A
authors.lastname: Moran
authors.forename: O H
authors.initials: OH
authors.lastname: Pescovitz
authors.forename: N J
authors.initials: NJ
authors.lastname: Charest
authors.forename: C M
authors.initials: CM
authors.lastname: Boney
authors.forename: J J
authors.initials: JJ
authors.lastname: Van Wyk
authors.forename: M J
authors.initials: MJ
authors.lastname: Merino
authors.forename: P P
authors.initials: PP
authors.lastname: Feuillan
authors.forename: A M
authors.initials: AM
authors.lastname: Spiegel
mesh_terms: D000293:Adolescent; D016375:Antisense Elements (Genetics); D001120:Arginine / Q000235:genetics*; D000242:Cyclic AMP / Q000235:genetics; D003645:Death, Sudden / Q000453:epidemiology; D004700:Endocrine System Diseases / Q000235:genetics; D005260:Female; D005359:Fibrous Dysplasia, Polyostotic / Q000150:complications / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009030:Mosaicism; D009154:Mutation; D016133:Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D016375:Antisense Elements (Genetics); D001120:Arginine; D000242:Cyclic AMP; D019204:GTP-Binding Proteins