McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

Orphanet J Rare Dis. 2012 May 24;7 Suppl 1(Suppl 1):S4. doi: 10.1186/1750-1172-7-S1-S4. Epub 2012 May 24.


Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS). The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues.The complexity can be mastered by a systematic screening of potentially involved tissues and cognizance that the pattern of involved tissues is established, to some degree, in utero. Thorough testing allows the clinician to establish, often times at presentation, the full extent of the disease, and importantly as well what tissues are unaffected. Treatment and follow-up can then be focused on affected systems and a meaningful prognosis can be offered to the patient and family. The authors outline screening and treatment strategies that allow for effective management of the extraskeletal manifestations of FD.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acromegaly / complications
  • Acromegaly / diagnosis
  • Acromegaly / drug therapy
  • Acromegaly / genetics
  • Aromatase Inhibitors / pharmacology
  • Cafe-au-Lait Spots / complications
  • Cafe-au-Lait Spots / diagnosis
  • Cafe-au-Lait Spots / drug therapy
  • Cafe-au-Lait Spots / genetics
  • Chromogranins
  • Cohort Studies
  • Cushing Syndrome / diagnosis
  • Cushing Syndrome / drug therapy
  • Cushing Syndrome / genetics
  • Fibroblast Growth Factor-23
  • Fibrous Dysplasia of Bone / complications*
  • Fibrous Dysplasia of Bone / diagnosis
  • Fibrous Dysplasia of Bone / drug therapy
  • Fibrous Dysplasia of Bone / genetics
  • Fibrous Dysplasia, Polyostotic / complications*
  • Fibrous Dysplasia, Polyostotic / diagnosis
  • Fibrous Dysplasia, Polyostotic / drug therapy
  • Fibrous Dysplasia, Polyostotic / genetics
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Humans
  • Hyperthyroidism / complications
  • Hyperthyroidism / diagnosis
  • Hyperthyroidism / drug therapy
  • Hyperthyroidism / genetics
  • Hypophosphatemia / complications
  • Hypophosphatemia / diagnosis
  • Hypophosphatemia / drug therapy
  • Mutation
  • Physical Examination
  • Puberty, Precocious / complications
  • Puberty, Precocious / diagnosis
  • Puberty, Precocious / drug therapy


  • Aromatase Inhibitors
  • Chromogranins
  • FGF23 protein, human
  • Fibroblast Growth Factor-23
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs

Supplementary concepts

  • Growth hormone excess