McCune-Albright syndrome
| McCune-Albright syndrome | |
| ICD-10 | Q78.1 |
|---|---|
| ICD-9 | 756.54 |
| OMIM | 174800 |
| DiseasesDB | 7880 |
| MedlinePlus | 001217 |
| eMedicine | ped/1386 |
| MeSH | D005359 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
McCune-Albright syndrome is a rare genetic disorder caused by an activating mutation of the GNAS gene resulting in various phenotypic presentations. MAS typically presents with the triad of polyostotic fibrous dysplasia, precocious puberty and café au lait spots in both genders. Other manifestations include hyperthyroidism, acromegaly and Cushing’s syndrome.[1]
Historical Perspective
- McCune-Albright syndrome was first discovered by physicians Donovan McCune and Fuller Albright in 1937. [2]
Classification
Pathophysiology
- The pathogenesis of McCune-Albright syndrome is characterized by increased cAMP signaling in bone, skin and endocrine tissues. In bone osteoblasts differentiation results in fibrous dysplasia. In the skin there is stimulation of melanin production resulting in café au lait macules with irregular borders. In endocrine tissues increased cAMP results in increased production of hormones depending on which tissue is affected including the gonads, thyroid, parathyroid, pituitary and adrenal glands.[1]
- The GNAS gene mutation has been associated with the development of McCune-Albright syndrome, involving the cAMP pathway-associated G-protein, Gsα. The various tissues involved in the syndrome is a result of the ubiquitous signaling of Gsα. [3]
Causes
McCune-Albright syndrome is caused by a missense mutation of the GNAS gene alpha subunit which becomes constitutively activated. This increases intracellular cAMP which activates downstream hormones resulting in multiple tissue types being affected and mosaicism presented in its patients. [1]
Differentiating McCune-Albright syndrome from other Diseases
For further information about the differential diagnosis, click here
Epidemiology and Demographics
Risk Factors
Natural History, Complications and Prognosis
- If left untreated patients may progress to develop decreased adult stature as a result of precocious puberty. [1]
- Common complications of McCune-Albright syndrome include rickets because of phosphate wasting and pain and fractures at fibrous dysplasia sites. [1]
Diagnosis
Diagnostic Criteria
- The diagnosis of McCune-Albright syndrome is a clinical diagnosis. [1]
- Though there are genetic tests available for the GNAS gene mutation with new PCR techniques for those who show clinical signs of the syndrome. [4]
- Patients who present with monostotic fibrous dysplasia are required to have evidence of the pathogenic GNAS gene my molecular testing [3]
Symptoms
 |
- Symptoms of McCune-Albright syndrome include the following:
- Precocious puberty
- Fibrous dysplasia leading to pathologic fractures or pain [1]
- Café au lait spots with “coast of Maine” irregular borders [1] and are often the first presenting sign [3]
- Possible hyperthyroidism, Cushing syndrome, acromegaly or prolactin secretion due to increased thyroid, cortisol, growth hormone or prolactin secretion respectively [1]
- Phosphate wasting with or without hypophosphatemia [3]
Physical Examination
Laboratory Findings
- Girls will have raised estradiol levels indicating an activated hypothalamic-pituitary axis.
- Other laboratory findings consistent with the diagnosis of McCune-Albright syndrome are elevated growth hormone which can be deduced by an oral glucose tolerance test, serum GH and prolactin measurements.
- Evaluation of hyperthyroidism is indicated by measuring TSH, free and bound thyroxine and T3.
- It is worth monitoring levels of serum phosphate and renal absorption of phosphate. [1]
Electrocardiogram
X-ray
The fibrous dysplasia of bone is present at multiple sites (polyostotic) and xrays would give a ground glass appearance. [4]
Echocardiography or Ultrasound
US in boys may be helpful in the diagnosis of McCune-Albright syndrome. Findings on an US suggestive of McCune-Albright syndrome include testicular ultrasounds to identify hormonally active tumors.[1]
CT scan
CT scan may be helpful in the diagnosis of McCune-Albright syndrome. Findings on CT scan suggestive of/diagnostic of McCune-Albright syndrome include fibroblastic lesions. It is helpful to identify these early in children to prevent permanent deformities. [1]
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
- The treatment for McCune Albright syndrome includes:
- Precocious puberty- prevent bone age advancement [3]
- For girls- Letrozole (aromatase inhibitor) and or tamoxifen (estrogen receptor modulator) [4]
- Fibrous dysplasia – minimize morbidity related to pain and fractures: [3]
- Bisphosphonates have been used for fibrous dysplasia pain. [4]
- Endocrinopathies
- Precocious puberty- prevent bone age advancement [3]
Surgery
Prevention
- Once diagnosed patients with McCune-Albright syndrome are followed-up with:
- Females – early breast cancer screening [3]
- Males – testicular lesions by physical examination and US [3]
- Both genders – signs of precocious puberty, growth hormone excess or growth acceleration, monitoring thyroid function, radiographs for fibrous dysplasia lesions particularly to check for scoliosis, serum phosphorous to monitor for development of hypophosphatemia [3] and regular vision and hearing testing to monitor fibrotic lesions affecting these areas. [1]
- Parents should be counseled that McCune-Albright syndrome is not inherited [3]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 "StatPearls". 2020. PMID 30725777.
- ↑ Manring MM, Calhoun JH (2011). "Biographical sketch: Fuller Albright, MD 1900-1969". Clin Orthop Relat Res. 469 (8): 2092–5. doi:10.1007/s11999-011-1831-0. PMC 3126964. PMID 21384213.
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 25719192.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL; et al. (2012). "Medical Genetics Summaries". PMID 28520344.