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

McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

Michael T Collins  1 , Frederick R Singer, Erica Eugster
Affiliations
Review

McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

Michael T Collins et al. Orphanet J Rare Dis. .

Abstract

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.

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Figures

Figure 1
Figure 1
The relative age at which any given aspect of the disease becomes clinically evident is depicted by a solid black bar. Preclinical disease is depicted by gray bars, and ages during which spontaneous resolution is possible for Cushing’s disease and phosphaturia are shown in open bars. The period of time during which abnormal menstruation can be expected is depicted by the stippled bar.
Figure 2
Figure 2
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.
Figure 3
Figure 3
Clinical and ultrasound findings of thyroid involvement in FD/MAS. Panels A & B demonstrate the findings in a 9-year-old girl with MAS and hyperthyroidism. A goiter is clearly seen on inspection (A) and the ultrasound (B) shows the typical cystic (Swiss cheese) appearance that seen in MAS thyroids. Panels C & D demonstrate the findings of a 30-year-old woman with MAS. While no goiter was evident on inspection, nor was one obvious on palpation, the ultrasound clearly demonstrated the typical findings seen in ultrasounds of patients with MAS and thyroid involvement. Adapted from reference [13.]
Figure 4
Figure 4
Panel A demonstrates the relationship and significant negative correlation between serum FGF23 and the degree of phosphate wasting, supporting the concept that FGF23 is responsible for the phosphate wasting that can be seen in association with FD. Panel B depicts the relationship and significant positive correlation between the serum FGF23 and the skeletal burden of FD, which supports the hypothesis that the FD tissue is the source of FGF23. Panels C&D are low and high power views, respectively, of in situ hybridization studies using probes for FGF23 that demonstrate that FD tissue demonstrates high levels of FGF23 transcripts. Panels E&F show high levels of FGF23 transcripts in bone from control, normal bone; E osteocytes and F osteoblasts in healing fracture callus. FD = fibrous dysplasia, wb = woven bone, b = bone, double arrows designate FD stromal cells, arrow heads designate osteocytes, single arrows designate osteoblasts. Adapted from reference [17].
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