FaCD Online Syndrome Fact Sheet

Last updated: 03 Mar 2011

Name: McCune-Albright syndrome

Synonym: Polyostotic Fibrous Dysplasia; MAS

Mode of Inheritance: de novo (mosaic)/ AD

Genes

GNAS1, mapped to 20q13.2

Tumor features

gastrointestinal hamartomas
gastrointestinal polyps, Peutz-Jeghers type
hamartomatous polyps in small intestine
intramuscular myxoma
osteosarcoma
pituitary adenoma
thyroid hyperplasia / goitre

Tumor features (possible)

breast cancer
gastric hamartomatous polyps
meningioma
thyroid cancer, clear cell
thyroid cancer, papillary

Non-tumor features

acromegaly
adrenal hyperplasia
bone, fibrous dysplasia & sclerosis of
bone, frequent fractures of
café au lait spots
lips, pigmentation of
oral mucosa, pigmentation of
perineal skin, hyperpigmentation of
sexual precocity
sexual precocity, female
sexual precocity, male
skeletal dysplasia

Comment

This disorder (MAS) is characterized by bone lesions (fibrous dysplasia) occurring at multiple sites, large cafe-au-lait spots of the skin with irregular margins, and a range of endocrine abnormalities, including hyperthyroidism (diffuse hyperplasia of the thyroid, sometimes multinodular goiter[8]), acromegaly (may be associated with pituitary adenoma[1-3]), Cushing syndrome (adrenal hyperplasia) and sexual precocity[4].[10,11]. The bone lesions are often asymmetric and usually appear before the age of 10 year. The sites most frequently affected are tibia, femur, pelvis, phalanges, ribs, humerus and the base of the skull. The bone lesions may become malignant (osteosarcoma). Meningioma has been reported in two patients[5] and thyroid cancer as well[6]. Ductal carcinoma in situ was reported in a 27-year-old woman with McCune-Albright syndrome, which lead the authors to suggest that persistent hyperestrogenism after precocious puberty associated with this syndrome may increase breast cancer risk[9].

Zacharin et al[12] reported endoscopy results in two MAS patients with perioral freckling (one of them also had perianal freckling), resembling Peutz-Jeghers syndrome (PJS), and in two MAS patients without such pigmentation. Hamartomatous gastrointestinal polyps of the PJS type were observed in all 4 subjects, only in the stomach and/or upper duodenum. Three of 4 subjects had documented GNAS mutations in peripheral blood and none had detectable STK11 gene (Peutz-Jeghers syndrome) or PRKAR1A gene (Carney complex) mutations. GNAS1 analysis in the polyps supported involvement of GNAS1 in polyp development. Together, this suggests an overlap between Peutz-Jeghers syndrome and MAS.

MAS is caused by the presence of mutations in the GNAS1 gene in a percentage of the cells, a phenomenon referred to as somatic mosaicism for that mutation[7]. It is not clear whether the few rare pedigrees with affected successive generations truly had McCune-Albright syndrome.

Links

The MAGIC Foundation for Children's Growth - McCune-Albright Syndrome Division 24 1 08

References

[1] Dotsch J, Kiess W, Hanze J, Repp R, Ludecke D, Blum WF, Rascher W. Clinical case seminar: G(s)alpha mutation at codon 201 in pituitary adenoma causing gigantism in a 6-year-old boy with McCune-Albright syndrome. J Clin Endocrinol Metab 81[11], 3839-3842. 1996.
[2] Gessl A, Freissmuth M, Czech T, Matula C, Hainfellner JA, Buchfelder M, Vierhapper H. Growth hormone-prolactin-thyrotropin-secreting pituitary adenoma in atypical McCune-Albright syndrome with functionally normal Gs alpha protein. J Clin Endocrinol Metab 1994; 79(4):1128-1134.
[3] Chung KF, Alaghband Zadeh J, Guz A. Acromegaly and hyperprolactinemia in McCune-Albright syndrome. Evidence of hypothalamic dysfunction. Am J Dis Child 1983; 137(2):134-136.
[4] Shenker A, Weinstein LS, Moran A, Pescovitz OH, Charest NJ, Boney CM, Van Wyk JJ, Merino MJ, Feuillan PP, Spiegel AM. Severe endocrine and nonendocrine manifestations of the McCune- Albright syndrome associated with activating mutations of stimulatory G protein GS. J Pediat 1993; 123(4):509-518.
[5] Fehlow P, Walther F, Assmann H. [McCune-Albright syndrome in association with meningioma and mental and psychological retardation]. Klin Padiatr 1992; 204(6):447-452.
[6] Collins MT, Sarlis NJ, Merino MJ, Monroe J, Crawford SE, Krakoff JA, Guthrie LC, Bonat S, Robey PG, Shenker A. Thyroid carcinoma in the McCune-Albright syndrome: contributory role of activating Gs alpha mutations. The Journal of clinical endocrinology and metabolism 2003; 88(9):4413-7.
[7] Ringel MD, Schwindinger WF, Levine MA. Clinical implications of genetic defects in G proteins: The molecular basis of McCune-Albright syndrome and Albright hereditary osteodystrophy. Medicine 75[4], 171-184. 1996.
[8] Congedo V, Celi FS. Thyroid disease in patients with McCune-Albright syndrome. Pediatric endocrinology reviews : PER 2007; 4 Suppl 4():429-33.
[9] Huston TL, Simmons RM. Ductal carcinoma in situ in a 27-year-old woman with McCune-Albright syndrome. The breast journal 2004 Sep-Oct; 10(5):440-2.
[10] Zacharin M. The spectrum of McCune Albright syndrome. Pediatric endocrinology reviews : PER 2007; 4 Suppl 4():412-8.
[11] Chanson P, Salenave S, Orcel P. McCune-Albright syndrome in adulthood. Pediatric endocrinology reviews : PER 2007; 4 Suppl 4():453-62.
[12] Zacharin M, Bajpai A, Chow CW, Catto-Smith A, Stratakis C, Wong MW, Scott R. Gastrointestinal polyps in McCune Albright syndrome. J Med Genet. 2011 Feb 28. [Epub ahead of print]