McCune-Albright syndrome

McCune-Albright syndrome (MAS) is a rare genetic disorder caused by somatic (postzygotic) activating mutations in the GNAS gene, which encodes the stimulatory G-protein alpha subunit (Gsα). Because the mutation occurs after conception during early embryonic development, it results in a mosaic pattern of affected cells throughout the body. The classic triad of McCune-Albright syndrome includes polyostotic fibrous dysplasia (replacement of normal bone with fibrous tissue, leading to fractures, deformity, and pain), café-au-lait skin pigmentation (irregularly bordered, hyperpigmented macules that typically respect the midline), and precocious puberty (most commonly gonadotropin-independent in girls, presenting as early breast development and vaginal bleeding). However, the clinical spectrum is highly variable depending on which tissues carry the mutation. Beyond the classic triad, MAS can involve autonomous hyperfunction of multiple endocrine glands. Hyperthyroidism, growth hormone excess (leading to gigantism or acromegaly), Cushing syndrome from adrenal hyperplasia, and renal phosphate wasting (hypophosphatemia) are well-recognized features. Hepatic, cardiac, and other organ involvement may also occur. Fibrous dysplasia can affect any bone but commonly involves the skull, femur, and pelvis, potentially causing significant skeletal morbidity including craniofacial asymmetry, scoliosis, and pathologic fractures. There is no cure for McCune-Albright syndrome, and treatment is directed at managing individual manifestations. Bisphosphonates (such as pamidronate) are used to manage bone pain associated with fibrous dysplasia, though their effect on fracture prevention remains uncertain. Aromatase inhibitors (such as letrozole) and anti-estrogens (such as tamoxifen) may be used to manage precocious puberty in girls. Hyperthyroidism and growth hormone excess are treated with targeted medical or surgical therapies. Orthopedic interventions, including intramedullary rodding, may be necessary for fractures and skeletal deformities. Lifelong multidisciplinary follow-up involving endocrinology, orthopedics, and other specialties is essential for optimal management.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about McCune-Albright syndrome