From Medical Genetics SummariesMcCune-Albright Syndrome (MAS) is a rare genetic disorder originally characterized as the triad of polyostotic fibrous dysplasia of bone, precocious puberty, and café-au-lait skin pigmentation. With time other associated endocrinopathies have been recognized, including hyperthyroidism, growth hormone excess, FGF23-mediated phosphate wasting, and hypercortisolism. MAS is caused by an activating mutation in the GNAS gene, which encodes the alpha subunit of the stimulatory G protein involved in G-protein signaling. A missense mutation, typically Arg201Cys or Arg201His (NM_001077488.3:c.604C>T, rs11554273), impairs the intrinsic GTPase activity of the Gsα protein, resulting in the constitutive activation of the Gsα-cAMP signaling pathway in the cells that contain the mutation. The mutation arises early in embryogenesis and is distributed in a mosaic pattern. The clinical phenotype is therefore highly variable, depending upon the location and timing of the mutation during embryologic development. Skin manifestations are common and are usually present at or shortly after birth. The café-au-lait spots typically have irregular margins giving them a “coast of Maine” appearance, and usually show an association with the midline of the body. In MAS, fibrous dysplasia of bone typically occurs at several sites (polyostotic), and commonly presents with fracture, deformity and/or bone pain. Radiographs show characteristic expansile lesions with a “ground glass” appearance. Craniofacial fibrous dysplasia can be severe in individuals who have pituitary disorders leading to hypersecretion of growth hormone. Treatment can be challenging and should begin as soon as possible. In girls, precocious puberty is a common initial manifestation, with recurrent ovarian cysts leading to episodes of vaginal bleeding and breast development. Precocious puberty is less common in boys, presenting with penile enlargement, pubic and axillary hair, acne, body odor, and sexual behavior. However, in both girls and boys, there is a high frequency of gonadal pathology (ovarian abnormalities in girls, and testicular abnormalities in boys).
https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/books/NBK66130 From OMIMActivating or gain-of-function GNAS1 mutations in patients with the McCune-Albright syndrome (MAS) are present in the mosaic state, resulting from a postzygotic somatic mutation appearing early in the course of development which yields a monoclonal population of mutated cells within variously affected tissues. The nonmosaic state for most activating mutations is presumably lethal to the embryo. The disorder is characterized clinically by the classic triad of polyostotic fibrous dysplasia (POFD), cafe-au-lait skin pigmentation, and peripheral precocious puberty. However, the disorder is clinically heterogeneous and can include various other endocrinologic anomalies such as thyrotoxicosis, pituitary gigantism, and Cushing syndrome (219080) (Lumbroso et al., 2004).
http://www.omim.org/entry/174800 From MedlinePlus GeneticsMcCune-Albright syndrome is a disorder that affects the bones, skin, and several hormone-producing (endocrine) tissues.
People with McCune-Albright syndrome develop areas of abnormal scar-like (fibrous) tissue in their bones, a condition called polyostotic fibrous dysplasia. Polyostotic means the abnormal areas (lesions) may occur in many bones; often they are confined to one side of the body. Replacement of bone with fibrous tissue may lead to fractures, uneven growth, and deformity. When lesions occur in the bones of the skull and jaw it can result in uneven (asymmetric) growth of the face. Asymmetry may also occur in the long bones; uneven growth of leg bones may cause limping. Abnormal curvature of the spine (scoliosis) may also occur. Bone lesions may become cancerous, but this happens in fewer than 1 percent of people with McCune-Albright syndrome.
In addition to bone abnormalities, affected individuals usually have light brown patches of skin called café-au-lait spots, which may be present from birth. The irregular borders of the café-au-lait spots in McCune-Albright syndrome are often compared to a map of the coast of Maine. By contrast, café-au-lait spots in other disorders have smooth borders, which are compared to the coast of California. Like the bone lesions, the café-au-lait spots in McCune-Albright syndrome may appear on only one side of the body.
Girls with McCune-Albright syndrome may reach puberty early. These girls often have menstrual bleeding by age 2. This early onset of menstruation is believed to be caused by excess estrogen, a female sex hormone, produced by cysts that develop in one of the ovaries. Less commonly, boys with McCune-Albright syndrome may also experience early puberty.
Other endocrine problems may also occur in people with McCune-Albright syndrome. The thyroid gland, a butterfly-shaped organ at the base of the neck, may become enlarged (a condition called a goiter) or develop masses called nodules. About 50 percent of affected individuals produce excessive amounts of thyroid hormone (hyperthyroidism), resulting in a fast heart rate, high blood pressure, weight loss, tremors, sweating, and other symptoms. The pituitary gland (a structure at the base of the brain that makes several hormones) may produce too much growth hormone. Excess growth hormone can result in acromegaly, a condition characterized by large hands and feet, arthritis, and distinctive facial features that are often described as "coarse." Excess growth hormone secretion may also lead to increased expansion of the fibrous dysplasia in the bones, most visibly in the skull. Rarely, affected individuals develop Cushing syndrome, an excess of the hormone cortisol produced by the adrenal glands, which are small glands located on top of each kidney. Cushing syndrome causes weight gain in the face and upper body, slowed growth in children, fragile skin, fatigue, and other health problems. In people with McCune-Albright syndrome, Cushing syndrome occurs only before age 2.
Problems in other organs and systems, such as noncancerous (benign) gastrointestinal growths called polyps and other abnormalities, can also occur in McCune-Albright syndrome.
https://medlineplus.gov/genetics/condition/mccune-albright-syndrome