Fibrous Dysplasia/McCune-Albright Syndrome: A Rare, Mosaic Disease of Gα s Activation

Endocr Rev. 2020 Apr 1;41(2):345-370. doi: 10.1210/endrev/bnz011.


Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare disorder of striking complexity. It arises from somatic, gain-of-function mutations in GNAS, leading to mosaic Gα s activation and inappropriate production of intracellular cyclic adenosine monophosphate (cAMP). The clinical phenotype is largely determined by the location and extent of affected tissues, and the pathophysiological effects of Gα s activation within these tissues. In bone, Gα s activation results in impaired differentiation of skeletal stem cells, leading to discrete skeletal lesions prone to fracture, deformity, and pain. Extraskeletal manifestations include a variable combination of hyperpigmented macules and hyperfunctioning endocrinopathies. Distinctive age-related changes in disease development has key effects on histologic, radiographic, and clinical features. FD/MAS thus presents along a uniquely broad clinical spectrum, and the resulting challenges in diagnosis and management can be difficult for clinicians. This review presents FD/MAS in the context of a mosaic disorder of Gα s activation, providing an intellectual framework within which to understand, evaluate, and treat this interesting disease. It includes a comprehensive summary of current understanding of FD/MAS pathogenesis, and a detailed discussion of clinical presentation and management. Critical areas of unmet need are highlighted, including discussion of key challenges and potential solutions to advance research and clinical care in FD/MAS.

Keywords: fibroblast growth factor 23; growth hormone excess; metabolic bone disease; precocious puberty; skeletal stem cells; somatic mosaicism.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Fibrous Dysplasia, Polyostotic* / diagnosis
  • Fibrous Dysplasia, Polyostotic* / metabolism
  • Fibrous Dysplasia, Polyostotic* / pathology
  • Fibrous Dysplasia, Polyostotic* / therapy
  • GTP-Binding Protein alpha Subunits*
  • Humans
  • Mosaicism*


  • GTP-Binding Protein alpha Subunits