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 Donovan McCune and Fuller Albright, both physicians 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]
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]
Differentiation McCune-Albright syndrome from other Diseases
Epidemiology and Demographics
Risk Factors
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Criteria
- The diagnosis of McCune-Albright syndrome is a clinical diagnosis. [1]
Symptoms
- Symptoms of McCune-Albright syndrome include the following:
- Precocious puberty
- Fibrous dysplasia leading to pathologic fractures or pain
- Café au lait spots with “coast of Maine” irregular borders
- Possible hyperthyroidism, Cushing syndrome, acromegaly or prolactin secretion due to increased thyroid, cortisol, growth hormone or prolactin secretion respectively [1]
Physical Examination
Laboratory Findings
- 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
Echocardiography or Ultrasound
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
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]
Other Diagnostic Studies
Treatment
Medical Therapy
- Regular vision and hearing testing to monitor fibrotic lesions affecting these areas. [1]