McCune–Albright syndrome

A rare mosaic disorder caused by activating mutations in GNAS. Its classic features are café-au-lait skin patches, fibrous dysplasia of bone, and endocrine hyperfunction.

GNAS: A gene encoding the stimulatory G-protein alpha subunit, which helps regulate cyclic AMP signaling. Activating mutations in GNAS drive the excess signaling underlying the syndrome.
Fibrous dysplasia: A bone disorder in which normal bone is replaced by fibro-osseous tissue. This is the characteristic skeletal lesion in McCune–Albright syndrome.
Mosaic variant analysis: Testing methods designed to detect genetic variants present in only a fraction of cells. Low-level GNAS mosaicism can be missed in blood, making affected tissue valuable for testing.
Neurofibromatosis type 1: An inherited tumor-predisposition disorder caused by pathogenic variants in NF1, often featuring café-au-lait macules. Its skin patches can resemble those of McCune–Albright syndrome, but its genetics and associated signs differ.
Somatic mosaicism: The presence of genetically distinct cell populations within one individual, arising from mutations after fertilization. The mutation occurs after fertilization, so only some tissues carry it.
Café-au-lait macule: A flat, light-brown skin patch caused by increased melanin pigmentation. The syndrome produces irregularly bordered patches that often respect the midline.
Bone scintigraphy: Nuclear medicine imaging that maps areas of bone turnover using a radiotracer. It can reveal the distribution of skeletal lesions across the body.
Jaffe–Lichtenstein syndrome: The combination of fibrous dysplasia and café-au-lait pigmentation without the endocrine features of McCune–Albright syndrome. It shares skin and bone findings but lacks the syndrome’s characteristic endocrine hyperfunction.
Gs alpha subunit: The alpha component of the stimulatory G protein that activates adenylyl cyclase when bound to GTP. Mutant Gs alpha remains active, increasing signaling in affected cells.
Endocrine system: The network of glands and cells that release hormones into the body. Endocrine hyperfunction is a defining feature alongside skin and bone findings.

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