McCune-Albright syndrome (MAS)

(OMIM phenotype number #174800)

McCune-Albright syndrome (MAS) is rare disease caused by an early embryonic postzygotic somatic activating mutations in the GNAS1 gene, encoding the cAMP pathway-associated G-protein, Gsα. The estimated prevalence is between 1/100.000 and 1/1.000.000. MAS is classically defined by the triad of fibrous dysplasia (FD), hyperpigmented (café-au-lait) skin lesions, and gonadotropin-independent sexual precocity. Moreover, MAS can include other endocrinopathies, such as hyperthyroidism, growth hormone excess, renal phosphate wasting with or without rickets/osteomalacia and Cushing syndrome. Rarely, other organ systems may be involved (i.e. liver, cardiac, parathyroid, and pancreas).

Diagnosis of MAS is based on the finding of two or more typical clinical features. The prognosis of the disease is based on lesions location and severity. Malignant transformation of FD lesions occurs in probably less than 1% of the cases of MAS. Differential diagnoses include: neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm.

Treatment is based on the tissues affected. The therapeutic management include: surgical intervention, the use of bisphosphonates and strengthening exercises for FD. Treatment of all endocrinopathies is required.


GNAS gene, 20q13.32 (OMIM gene/locus number *139320)


Disorder that affects the bones, skin (café-au-lait pigmentation), and several endocrine tissues with possible precocious puberty, hyperthyroidism, excessive secretion of growth hormone,
Cushing syndrome, hyperparathyroidism, acromegaly, hyperprolactinemia, polyostotic fibrous dysplasia (scar-like/fibrous tissue in the bones, often confined to one side of the body), some cases of hypophosphatemic osteomalacia, and craniofacial hyperostosis.

Main biochemical alterations:

Normal-high Ca, normal-low Pi, normal-high PTH, normal/high 1-25(OH)2D3 + other endocrine abnormalities.


Fig. 1) Café-au-lait skin pigmentation. (a) Skin lesions in a newborn demonstrating the characteristic association with the midline of the body, and distribution reflecting patterns of embryonic cell migration (developmental lines of Blaschko). (b) A typical lesion on the chest, face, and arm demostrating the irregular "coast of Maine" borders, relationship with the midline of the body, and distribution following developmental lines of Blaschko. (c). Typical lesions frequently found on the nape of the neck and crease of the buttocks. 

Fig. 2) (a) Proximal femur FD demonstrating the typical ground glass appearance with a coxa vara (“shepherd’s crook”) deformity. (b) Three-dimensional reconstructed computed tomography (CT) image of a man age 26 years with craniofacial FD and uncontrolled growth hormone excess, leading to macrocephaly and severe facial deformity. 

Reproduced with permission and copyright © 1993-2015 of the University of Washington, Seattle. Boyce AM and Collins MT, Fibrous Dysplasia/McCune-Albright Syndrome In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews®




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