Mccune-Albright Syndrome (MAS)

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Disease Ontology 12 DOID:1858 OMIM 56 174800 604308 KEGG 36 H00501 H00661 ICD9CM 34 756.54 MeSH 43 D005357 D005359 NCIt 49 C34610 SNOMED-CT 67 10623005 36517007 ICD10 32 Q78.1

MESH via Orphanet 44 D005357 D005359 ICD10 via Orphanet 33 Q78.1 UMLS via Orphanet 72 C0016063 C0016065 C0242292 Orphanet 58 ORPHA249 ORPHA562 ORPHA93276 MedGen 41 C0016065 C0242292 C1858556 SNOMED-CT via HPO 68 103276001 105985007 109504005 123527003 12584003 126900000 126926005 127018007 128664001 134291007 15188001 15253005 166603001 166643006 201066002 201067006 22640007 22810007 237662005 237735008 240190009 2424003 248328003 254956000 263681008 268029009 269469005 275437005 343087000 34486009 35580009 3716002 400179000 409712001 414564002 424413001 424952003 47212006 47270006 4996001 5468008 62250003 65956007 66999008 67362008 69878008 74107003 75183008 76976005 8074002 80967001 88673001 95828007 more UMLS 71 C0016063 C0016065 C0242292

Genetics Home Reference : ²⁵ McCune-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.

MalaCards based summary : Mccune-Albright Syndrome, also known as mass syndrome, is related to fibrous dysplasia/mccune-albright syndrome and gigantism. An important gene associated with Mccune-Albright Syndrome is GNAS (GNAS Complex Locus), and among its related pathways/superpathways are Phospholipase-C Pathway and PI3K-Akt signaling pathway. The drugs Risedronate and Etidronic acid have been mentioned in the context of this disorder. Affiliated tissues include bone, skin and pituitary, and related phenotypes are hypophosphatemia and recurrent fractures

Disease Ontology : ¹² A syndrome that is characterized by polyostotic fibrous dysplasia, precocious puberty, and café-au-lait spots and has material basis in spontaneous post zygotic missense mutation at ARG201 or Gln227 of the GNAS gene during embryogenesis.

NIH Rare Diseases : ⁵² MASS phenotype is a familial connective tissue disorder similar to Marfan syndrome that affects different people in different ways. MASS is an acronym for features of the disorder that may be present: M itral valve prolapse - a heart condition in which the two valve flaps of the mitral valve in the heart do not close smoothly or evenly, and bulge (prolapse) upward into the left atrium. A ortic root dilation - borderline, non-progressive enlargement of the section of the aorta where the aorta and heart meet. Unlike in Marfan syndrome , aortic complications such as dissection and aneurysm usually do not occur. However some authors believe there may be an increased risk for aortic complications. S kin striae (stretch marks ) - skin may have stretch marks even without changes in weight. S keletal features - possible features include curvature of the spine (scoliosis ), chest wall deformities , and joint hypermobility . People with MASS phenotype also have nearsightedness (myopia), but they do not experience eye lens dislocation (ectopia lentis) as in Marfan syndrome. MASS phenotype has rarely been diagnosed in people with a mutation in the FBN1 gene (which usually causes Marfan syndrome), but in most cases the cause of MASS phenotype is not yet known. People diagnosed with MASS phenotype who do have a FBN1 mutation may later be diagnosed with Marfan syndrome as additional features develop, which would convey a high risk of aortic complications. It may be hard to distinguish MASS phenotype from early features of Marfan syndrome in young individuals. Management focuses on the specific symptoms and severity in each person. It is important to monitor signs and symptoms over time, such as having annual heart and eye exams. This is especially important for people under 20 years of age who potentially have Marfan syndrome, since additional features may develop with age.

OMIM : ⁵⁶ Activating or gain-of-function GNAS1 mutations in patients with the McCune-Albright syndrome 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). (174800)

KEGG : ³⁶ Polyostotic fibrous dysplasia is a condition of subcutaneous ossification associated with short stature, round face and brachydactyly. Mosaic GNAS mutations that results in abnormal differentiation of osteoblastic cells are responsible for the condition.

UniProtKB/Swiss-Prot : ⁷³ McCune-Albright syndrome: Characterized by polyostotic fibrous dysplasia, cafe-au-lait lesions, and a variety of endocrine disorders, including precocious puberty, hyperthyroidism, hypercortisolism, growth hormone excess, and hyperprolactinemia. The mutations producing MAS lead to constitutive activation of GS alpha.
Overlap connective tissue disease: Heritable disorder of connective tissue characterized by involvement of the mitral valve, aorta, skeleton, and skin. MASS syndrome is closely resembling both the Marfan syndrome and the Barlow syndrome. However, no dislocation of the lenses or aneurysmal changes occur in the aorta, and the mitral valve prolapse is by no means invariable.

Wikipedia : ⁷⁴ McCune-Albright syndrome is a complex genetic disorder affecting the bone, skin and endocrine systems.... more...

Clinical features from OMIM:

174800 604308

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased viability	GR00240-S-1	9.4	SST
2	Decreased viability	GR00249-S	9.4	APC GH1 IGFBP3 SOST
3	Decreased viability	GR00381-A-1	9.4	GNAS
4	Decreased viability	GR00386-A-1	9.4	ADCY1 GNAS IBSP
5	Decreased viability	GR00402-S-2	9.4	DIO2 FBN1 IGFBP3

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