McCune-Albright Syndrome.

McCune-Albright syndrome (MAS) is an extremely heterogenous condition in which a variety of systemic and endocrine abnormalities can occur. It is classically characterized by the triad of peripheral precocious puberty, café au lait skin pigmentation, and polyostotic fibrous dysplasia of bone. It is caused by activating mutations of GNAS, the gene encoding the alpha subunit of the stimulatory G-protein (G_s α), and result in constitutive, ligand-independent activity in affected cells. The GNAS activating mutations lead to a loss of intrinsic guanosine triphosphatase (GTPase) activity of Gs α , resulting in an inability to return the cell to its inactive basal state after stimulation by a hormone ligand. Thus, the presence of GNAS mutations in endocrine cells is associated with unregulated hormone production and the development of endocrine cells is associated with unregulated hormone production and the development of endocrine hyperfunction. Diagnosis is based on careful physical examination as well as biochemical and radiographic evaluation, while molecular diagnosis is currently best reserved for the research setting. Therapeutic approaches vary widely and must be individualized to target the presiding manifestations of the disorder. Because MAS is both rare and heterogeneous in nature, collaborative and multi-center research efforts are paramount to advance the understanding of the etiology, pathophysiology, diagnosis and treatment of this condition. [ABSTRACT FROM AUTHOR]