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McCune–Albright Syndrome (MAS) is a rare, sporadic disorder characterized by a triad of:

Polyostotic fibrous dysplasia (FD)
Endocrine abnormalities (most notably precocious puberty)
Café-au-lait macules </aside>

It results from a somatic postzygotic activating mutation in the GNAS gene, leading to constitutive activation of Gsα protein and excessive cAMP signaling in affected tissues.

Etiopathogenesis

Genetic basis:

Gene involved: GNAS1 (guanine nucleotide-binding protein alpha subunit)
Mechanism: Activating mutation → constitutive activation of adenylyl cyclase → ↑ cAMP → dysregulated cell signaling
Mosaicism: The disease manifests only in tissues with the mutation due to its postzygotic nature.

Clinical features

Clinical triad:

Manifestation	Description
Polyostotic FD	Multiple bones involved with typical ground-glass lesions and deformities (e.g., femur)
Café-au-lait spots	Irregular “coast of Maine” margins, usually respecting the midline
Endocrinopathy	Gonadotropin-independent precocious puberty (especially in girls), thyroid disease, Cushing’s, acromegaly

![Clinical images in Fibrous Dysplasia/McCune-Albright Syndrome. A. Café-au-lait macules reflect along the spine of an adolescent girl (arrows), demonstrating typical jagged borders and distribution along the midline of the body. Note the obliquity in this patient’s hips and shoulders, reflective of underlying scoliosis. B. Lentigines involving the oral mucosa (arrows) and outer lips (arrowhead) in an adult patient. C. Radiograph from the patient in panel A show severe scoliosis involving the thoracic and lumbar spine (arrows). Expansile FD lesions are apparent in the right 11th and 12th ribs (asterisks). The patient has a surgical implant visible in the proximal right femur related to a previous fracture repair. D. Three-dimensional computed tomography scan demonstrates multiple expansile FD lesions involving the calvarium, maxilla, and mandible (arrows). E. Pelvic ultrasound in a 3-year-old girl with pubertal symptoms and elevated estrogen levels reveals a large ovarian cyst (arrow). F. 18F-NaF PET/CT scan shows multiple areas of tracer uptake in the skull, ribs, spine, and long bones, consistent with polyostotic FD (arrows). Note the expected physiologic, symmetric uptake in the metaphyses throughout in this growing child.

de Castro LF, Ovejero D, Boyce AM. DIAGNOSIS OF ENDOCRINE DISEASE: Mosaic disorders of FGF23 excess: Fibrous dysplasia/McCune-Albright syndrome and cutaneous skeletal hypophosphatemia syndrome. European Journal of Endocrinology. 2020 May;182(5):R83-R99. DOI: 10.1530/eje-19-0969. PMID: 32069220; PMCID: PMC7104564.](attachment:cf676b65-761e-4f4a-9932-1ea1e816b97d:nihms-1565780-f0002.jpg)

Clinical images in Fibrous Dysplasia/McCune-Albright Syndrome. A. Café-au-lait macules reflect along the spine of an adolescent girl (arrows), demonstrating typical jagged borders and distribution along the midline of the body. Note the obliquity in this patient’s hips and shoulders, reflective of underlying scoliosis. B. Lentigines involving the oral mucosa (arrows) and outer lips (arrowhead) in an adult patient. C. Radiograph from the patient in panel A show severe scoliosis involving the thoracic and lumbar spine (arrows). Expansile FD lesions are apparent in the right 11th and 12th ribs (asterisks). The patient has a surgical implant visible in the proximal right femur related to a previous fracture repair. D. Three-dimensional computed tomography scan demonstrates multiple expansile FD lesions involving the calvarium, maxilla, and mandible (arrows). E. Pelvic ultrasound in a 3-year-old girl with pubertal symptoms and elevated estrogen levels reveals a large ovarian cyst (arrow). F. 18F-NaF PET/CT scan shows multiple areas of tracer uptake in the skull, ribs, spine, and long bones, consistent with polyostotic FD (arrows). Note the expected physiologic, symmetric uptake in the metaphyses throughout in this growing child.

![Representative Café-au-lait Spots Seen in McCune-Albright Syndrome. A spectrum of spots is shown; Panels A & B demonstrate “classic” spots that both respect the midline and display “coast of Maine” borders. Panel C shows a very unusual spot seen in a child with MAS and neonatal Cushing syndrome. While the spot respects the midline, the borders are smooth and the spots alternate from left to right in a harlequin pattern. Panel D depicts a very large spot with relatively smooth borders seen in a patient with relatively little FD. Panel E demonstrates a spot that clearly does not respect the midline.

Collins, M.T., Singer, F.R. & Eugster, E. McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia. Orphanet J Rare Dis 7 (Suppl 1), S4 (2012). https://doi.org/10.1186/1750-1172-7-S1-S4](attachment:c29cf659-6575-4ba3-bf9a-b3eb031fe34e:13023_2012_Article_374_Fig2_HTML.webp)

Representative Café-au-lait Spots Seen in McCune-Albright Syndrome. A spectrum of spots is shown; Panels A & B demonstrate “classic” spots that both respect the midline and display “coast of Maine” borders. Panel C shows a very unusual spot seen in a child with MAS and neonatal Cushing syndrome. While the spot respects the midline, the borders are smooth and the spots alternate from left to right in a harlequin pattern. Panel D depicts a very large spot with relatively smooth borders seen in a patient with relatively little FD. Panel E demonstrates a spot that clearly does not respect the midline.

Other endocrinopathies:

Hyperthyroidism
Growth hormone excess (leading to gigantism/acromegaly)
Neonatal Cushing’s syndrome (rare, often fatal)
Phosphate wasting (due to FGF-23 overproduction)