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McCune-Albright syndrome(MAS)

MedGen UID:
69164
Concept ID:
C0242292
Disease or Syndrome
Synonyms: Albright syndrome; Albright's disease; Albright's Syndrome; MAS; McCune-Albright syndrome, somatic, mosaic
SNOMED CT: McCune Albright syndrome (726029005); Albright's disease of bone (36517007); Albright syndrome (36517007)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): GNAS (20q13.32)
 
Monarch Initiative: MONDO:0018919
OMIM®: 174800
Orphanet: ORPHA562

Disease characteristics

Excerpted from the GeneReview: Fibrous Dysplasia / McCune-Albright Syndrome
Fibrous dysplasia / McCune-Albright syndrome (FD/MAS), the result of an early embryonic postzygotic somatic activating pathogenic variant in GNAS (encoding the cAMP pathway-associated G protein Gαs [Gs alpha subunit]), is characterized by involvement of the skin, skeleton, and certain endocrine organs. However, because Gαs signaling is ubiquitous, additional tissues may be affected. Hyperpigmented skin macules are common and are usually the first manifestation of the disease, apparent at or shortly after birth. Fibrous dysplasia (FD), which can involve any part and combination of the craniofacial, axial, and/or appendicular skeleton, can range from an isolated, asymptomatic monostotic lesion discovered incidentally to severe, disabling polyostotic disease involving practically the entire skeleton and leading to progressive scoliosis, facial deformity, and loss of mobility, vision, and/or hearing. Endocrinopathies include gonadotropin-independent precocious puberty resulting from recurrent ovarian cysts in girls and autonomous testosterone production in boys; testicular lesions with or without associated gonadotropin-independent precocious puberty; thyroid lesions with or without non-autoimmune hyperthyroidism; growth hormone excess; FGF23-mediated phosphate wasting with or without hypophosphatemia in association with fibrous dysplasia; and neonatal hypercortisolism. [from GeneReviews]
Authors:
Vivian Szymczuk  |  Pablo Florenzano  |  Luis F de Castro, et. al.   view full author information

Additional descriptions

From Medical Genetics Summaries
McCune-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://www.ncbi.nlm.nih.gov/books/NBK66130
From OMIM
Activating 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 Genetics
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.  https://medlineplus.gov/genetics/condition/mccune-albright-syndrome

Clinical features

From HPO
Pituitary adenoma
MedGen UID:
45933
Concept ID:
C0032000
Neoplastic Process
A benign epithelial tumor derived from intrinsic cells of the adenohypophysis (anterior pituitary).
Acral overgrowth
MedGen UID:
1789172
Concept ID:
C1735881
Disease or Syndrome
Excessive growth of hands and feet (predominantly due to soft tissue swelling). Typical manifestations include shoe size increase, foot enlargment, glove tightness, and hand enlargement.
Intestinal polyposis
MedGen UID:
219797
Concept ID:
C1257915
Disease or Syndrome
The presence of multiple polyps in the intestine.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Increased circulating prolactin concentration
MedGen UID:
1702649
Concept ID:
C5200994
Finding
The presence of abnormally increased levels of prolactin in the blood. Prolactin is a peptide hormone produced by the anterior pituitary gland that plays a role in breast development and lactation during pregnancy.
Polyostotic fibrous dysplasia of bone
MedGen UID:
5180
Concept ID:
C0016065
Neoplastic Process
Fibrous dysplasia of the bones were lesions are localized in many bones throughout of the body. Polyostotic fibrous dysplasia is a cardinal feature of McCune-Albright syndrome.
Pathologic fracture
MedGen UID:
42095
Concept ID:
C0016663
Pathologic Function
A pathologic fracture occurs when a bone breaks in an area that is weakened secondarily to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
Craniofacial hyperostosis
MedGen UID:
358122
Concept ID:
C1868085
Finding
Excessive growth of the craniofacial bones.
Facial asymmetry
MedGen UID:
266298
Concept ID:
C1306710
Finding
An abnormal difference between the left and right sides of the face.
Large cafe-au-lait macules with irregular margins
MedGen UID:
870720
Concept ID:
C4025174
Finding
Large hypermelanotic macules with jagged borders.
Hyperparathyroidism
MedGen UID:
6967
Concept ID:
C0020502
Disease or Syndrome
Excessive production of parathyroid hormone (PTH) by the parathyroid glands.
Hyperthyroidism
MedGen UID:
6972
Concept ID:
C0020550
Disease or Syndrome
An abnormality of thyroid physiology characterized by excessive secretion of the thyroid hormones thyroxine (i.e., T4) and/or 3,3',5-triiodo-L-thyronine zwitterion (i.e., triiodothyronine or T3).
Precocious puberty
MedGen UID:
18752
Concept ID:
C0034013
Disease or Syndrome
The onset of secondary sexual characteristics before a normal age. Although it is difficult to define normal age ranges because of the marked variation with which puberty begins in normal children, precocious puberty can be defined as the onset of puberty before the age of 8 years in girls or 9 years in boys.
Elevated circulating growth hormone concentration
MedGen UID:
66732
Concept ID:
C0235986
Finding
Acromegaly is a condition resulting from overproduction of growth hormone by the pituitary gland in persons with closed epiphyses, and consists chiefly in the enlargement of the distal parts of the body. The circumference of the skull increases, the nose becomes broad, the tongue becomes enlarged, the facial features become coarsened, the mandible grows excessively, and the teeth become separated. The fingers and toes grow chiefly in thickness.
Increased circulating cortisol level
MedGen UID:
871175
Concept ID:
C4025651
Finding
Overproduction of the hormone of cortisol by the adrenal cortex, resulting in a characteristic combination of clinical symptoms termed Cushing syndrome, with truncal obesity, a round, full face, striae atrophicae and acne, muscle weakness, and other features.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMcCune-Albright syndrome
Follow this link to review classifications for McCune-Albright syndrome in Orphanet.

Professional guidelines

PubMed

Vamvoukaki R, Chrysoulaki M, Betsi G, Xekouki P
Medicina (Kaunas) 2023 Apr 21;59(4) doi: 10.3390/medicina59040812. PMID: 37109772Free PMC Article
Spencer T, Pan KS, Collins MT, Boyce AM
Horm Res Paediatr 2019;92(6):347-356. Epub 2019 Dec 19 doi: 10.1159/000504802. PMID: 31865341Free PMC Article
Javaid MK, Boyce A, Appelman-Dijkstra N, Ong J, Defabianis P, Offiah A, Arundel P, Shaw N, Pos VD, Underhil A, Portero D, Heral L, Heegaard AM, Masi L, Monsell F, Stanton R, Dijkstra PDS, Brandi ML, Chapurlat R, Hamdy NAT, Collins MT
Orphanet J Rare Dis 2019 Jun 13;14(1):139. doi: 10.1186/s13023-019-1102-9. PMID: 31196103Free PMC Article

Recent clinical studies

Etiology

Spencer TL, Watts L, Soni A, Pinedo-Villanueva R, Heegaard AM, Boyce AM, Javaid MK
J Clin Endocrinol Metab 2022 May 17;107(6):e2258-e2266. doi: 10.1210/clinem/dgac120. PMID: 35262711Free PMC Article
Zhadina M, Roszko KL, Geels RES, de Castro LF, Collins MT, Boyce AM
J Clin Endocrinol Metab 2021 Apr 23;106(5):1482-1490. doi: 10.1210/clinem/dgab053. PMID: 33512531Free PMC Article
Javaid MK, Boyce A, Appelman-Dijkstra N, Ong J, Defabianis P, Offiah A, Arundel P, Shaw N, Pos VD, Underhil A, Portero D, Heral L, Heegaard AM, Masi L, Monsell F, Stanton R, Dijkstra PDS, Brandi ML, Chapurlat R, Hamdy NAT, Collins MT
Orphanet J Rare Dis 2019 Jun 13;14(1):139. doi: 10.1186/s13023-019-1102-9. PMID: 31196103Free PMC Article
Collins MT, Singer FR, Eugster E
Orphanet J Rare Dis 2012 May 24;7 Suppl 1(Suppl 1):S4. doi: 10.1186/1750-1172-7-S1-S4. PMID: 22640971Free PMC Article
Dumitrescu CE, Collins MT
Orphanet J Rare Dis 2008 May 19;3:12. doi: 10.1186/1750-1172-3-12. PMID: 18489744Free PMC Article

Diagnosis

Banerjee S, Bajpai A
Indian J Pediatr 2023 Jun;90(6):582-589. Epub 2023 Apr 19 doi: 10.1007/s12098-023-04554-4. PMID: 37074536
Boyce AM, Collins MT
Endocr Rev 2020 Apr 1;41(2):345-70. doi: 10.1210/endrev/bnz011. PMID: 31673695Free PMC Article
Spencer T, Pan KS, Collins MT, Boyce AM
Horm Res Paediatr 2019;92(6):347-356. Epub 2019 Dec 19 doi: 10.1159/000504802. PMID: 31865341Free PMC Article
Javaid MK, Boyce A, Appelman-Dijkstra N, Ong J, Defabianis P, Offiah A, Arundel P, Shaw N, Pos VD, Underhil A, Portero D, Heral L, Heegaard AM, Masi L, Monsell F, Stanton R, Dijkstra PDS, Brandi ML, Chapurlat R, Hamdy NAT, Collins MT
Orphanet J Rare Dis 2019 Jun 13;14(1):139. doi: 10.1186/s13023-019-1102-9. PMID: 31196103Free PMC Article
Hartley I, Zhadina M, Collins MT, Boyce AM
Calcif Tissue Int 2019 May;104(5):517-529. Epub 2019 Apr 29 doi: 10.1007/s00223-019-00550-z. PMID: 31037426Free PMC Article

Therapy

Cherian KE, Paul TV
Best Pract Res Clin Endocrinol Metab 2024 Mar;38(2):101844. Epub 2023 Nov 28 doi: 10.1016/j.beem.2023.101844. PMID: 38044258
Banerjee S, Bajpai A
Indian J Pediatr 2023 Jun;90(6):582-589. Epub 2023 Apr 19 doi: 10.1007/s12098-023-04554-4. PMID: 37074536
Kritmetapak K, Kumar R
Endocr Pract 2023 Jan;29(1):69-79. Epub 2022 Oct 7 doi: 10.1016/j.eprac.2022.09.007. PMID: 36210014
Huzum B, Antoniu S, Dragomir R
Expert Opin Biol Ther 2022 Mar;22(3):397-405. Epub 2021 Dec 29 doi: 10.1080/14712598.2022.2022118. PMID: 34964677
Robinson C, Collins MT, Boyce AM
Curr Osteoporos Rep 2016 Oct;14(5):178-86. doi: 10.1007/s11914-016-0317-0. PMID: 27492469Free PMC Article

Prognosis

Meier ME, Vágó E, Abrahamsen B, Dekkers OM, Horváth-Puhó E, Rejnmark L, Appelman-Dijkstra NM
J Clin Endocrinol Metab 2024 May 17;109(6):1423-1432. doi: 10.1210/clinem/dgad744. PMID: 38174586Free PMC Article
Huzum B, Antoniu S, Dragomir R
Expert Opin Biol Ther 2022 Mar;22(3):397-405. Epub 2021 Dec 29 doi: 10.1080/14712598.2022.2022118. PMID: 34964677
Zhadina M, Roszko KL, Geels RES, de Castro LF, Collins MT, Boyce AM
J Clin Endocrinol Metab 2021 Apr 23;106(5):1482-1490. doi: 10.1210/clinem/dgab053. PMID: 33512531Free PMC Article
Spencer T, Pan KS, Collins MT, Boyce AM
Horm Res Paediatr 2019;92(6):347-356. Epub 2019 Dec 19 doi: 10.1159/000504802. PMID: 31865341Free PMC Article
Collins MT, Singer FR, Eugster E
Orphanet J Rare Dis 2012 May 24;7 Suppl 1(Suppl 1):S4. doi: 10.1186/1750-1172-7-S1-S4. PMID: 22640971Free PMC Article

Clinical prediction guides

Meier ME, Hagelstein-Rotman M, Streefland TCM, Winter EM, Bravenboer N, Appelman-Dijkstra NM
Bone 2023 Jun;171:116744. Epub 2023 Mar 21 doi: 10.1016/j.bone.2023.116744. PMID: 36958543
Van Doan N, Minh Duc N, Kim Ngan V, Van Anh N
BMJ Case Rep 2021 Jul 19;14(7) doi: 10.1136/bcr-2021-243401. PMID: 34281944Free PMC Article
Zhadina M, Roszko KL, Geels RES, de Castro LF, Collins MT, Boyce AM
J Clin Endocrinol Metab 2021 Apr 23;106(5):1482-1490. doi: 10.1210/clinem/dgab053. PMID: 33512531Free PMC Article
Salenave S, Boyce AM, Collins MT, Chanson P
J Clin Endocrinol Metab 2014 Jun;99(6):1955-69. Epub 2014 Feb 11 doi: 10.1210/jc.2013-3826. PMID: 24517150Free PMC Article
Lietman SA, Levine MA
Pediatr Endocrinol Rev 2013 Jun;10 Suppl 2:389-96. PMID: 23858622

Recent systematic reviews

Bertin H, Moussa MS, Komarova S
Rev Endocr Metab Disord 2023 Dec;24(6):1103-1119. Epub 2023 Aug 26 doi: 10.1007/s11154-023-09832-2. PMID: 37632645
Jayant SS, Walia R, Gupta R, Pal R, Chaudhary S, Agrawal K, Rastogi A, Bhattacharya A, Dutta P, Bhadada SK, Bhansali A
Endocrine 2023 Jul;81(1):149-159. Epub 2023 Mar 6 doi: 10.1007/s12020-023-03333-7. PMID: 36877453
Yang L, Wu H, Lu J, Teng L
J Craniofac Surg 2017 Jan;28(1):21-25. doi: 10.1097/SCS.0000000000002830. PMID: 27922965
Pedersen MR, Rafaelsen SR, Møller H, Vedsted P, Osther PJ
Int Urol Nephrol 2016 Jul;48(7):1079-86. Epub 2016 Mar 23 doi: 10.1007/s11255-016-1267-2. PMID: 27007613
Lau D, Rutledge C, Aghi MK
Neurosurg Focus 2015 Feb;38(2):E11. doi: 10.3171/2014.10.FOCUS14700. PMID: 25639313

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