McCune Albright syndrome is a rare, sporadically occurring genetic disorder characterized by the clinical triad of polyostotic fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP). PP, the most characteristic feature of this disease, is far more common in girls than in boys, and is due to gonadotropin independent autonomous ovarian or testicular function. Other hyperfunctioning endocrinopathies, such as hyperthyroidism, growth hormone excess, Cushing's syndrome, hypercortisolism, pituitary gigantism, and acromegaly are also common. Fibrous dysplasia most commonly affects the long bones, ribs and skulls, leading to fractures and deformities. In the skull, the dysplasia can lead to blindness and deafness due to impingement on nerves. Non-endocrine abnormalities such as hypophosphatemia, chronic liver disease, tachycardia, and rarely, sudden death form cardiac arrythmias may also occur.

Specific treatment for the McCune Albright syndrome is not available. Aromatase inhibitors, like testolactone are prescribed for PP, to slow down the estrogen hypersecretion. Diphosphonates are used in case of evolutive FD. Adrenal abnormalities may be treated by surgery involving removal of the adrenal glands.

McCune Albright syndrome is the result of a postzygotic somatic mutation in the GNAS complex locus.

McCune Albright syndrome is the result of a postzygotic somatic mutation in the GNAS complex locus. This locus, located on chromosome 20, codes for multiple proteins, one of which is the Gs-alpha, the alpha subunit of the heterotrimeric stimulatory G protein. A specific mutation, commonly a substitution of histadine or cysteine for arginine at amino acid 201 in the Gs-alpha causes constitutive activation of the protein, even in the absence of hormonal stimulation, leading to increased cAMP levels and mitogenesis.