McCune-Albright syndrome: Difference between revisions
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==Pathophysiology== | ==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. | *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. | ||
*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. | *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. | ||
| Line 40: | Line 40: | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
*The prevalence of McCune-Albright syndrome is between 1:100,000 and 1:1,000,000 making it very rare. | *The prevalence of McCune-Albright syndrome is between 1:100,000 and 1:1,000,000 making it very rare. | ||
===Age=== | ===Age=== | ||
*McCune-Albright syndrome is more commonly observed among infants and young children. | *McCune-Albright syndrome is more commonly observed among infants and young children. | ||
| Line 74: | Line 74: | ||
*Symptoms of McCune-Albright syndrome include the following: | *Symptoms of McCune-Albright syndrome include the following: | ||
**Precocious puberty | **Precocious puberty | ||
***In girls presenting with ovarian cysts with vaginal bleeding and breast development | ***In girls presenting with ovarian cysts with vaginal bleeding and breast development | ||
***In boys presenting with acne, body odor, pubic hair and penile enlargement <ref name="pmid28520344">{{cite journal| author=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL | display-authors=etal| title=Medical Genetics Summaries | journal= | year= 2012 | volume= | issue= | pages= | pmid=28520344 | doi= | pmc= | url= }} </ref> | ***In boys presenting with acne, body odor, pubic hair and penile enlargement <ref name="pmid28520344">{{cite journal| author=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL | display-authors=etal| title=Medical Genetics Summaries | journal= | year= 2012 | volume= | issue= | pages= | pmid=28520344 | doi= | pmc= | url= }} </ref> | ||
***Both genders with gonadal pathologies <ref name="pmid28520344">{{cite journal| author=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL | display-authors=etal| title=Medical Genetics Summaries | journal= | year= 2012 | volume= | issue= | pages= | pmid=28520344 | doi= | pmc= | url= }} </ref> | ***Both genders with gonadal pathologies <ref name="pmid28520344">{{cite journal| author=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL | display-authors=etal| title=Medical Genetics Summaries | journal= | year= 2012 | volume= | issue= | pages= | pmid=28520344 | doi= | pmc= | url= }} </ref> | ||
| Line 94: | Line 94: | ||
**Pubic and or axillary hair and penile enlargement in males | **Pubic and or axillary hair and penile enlargement in males | ||
**Growth acceleration in both genders | **Growth acceleration in both genders | ||
**Cushingoid features due to hypercortisolism | **Cushingoid features due to hypercortisolism | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Revision as of 19:06, 19 August 2020
| 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] Associate Editor-in-Chief: Dushka Riaz, MD
Overview
McCune-Albright syndrome is a rare genetic disorder caused by an activating mutation of the GNAS gene resulting in various phenotypic presentations. McCune-Albright syndrome typically presents with the triad of fibrous dysplasia, precocious puberty and café au lait spots in both genders. Other manifestations include hyperthyroidism, acromegaly and Cushing’s syndrome.
Historical Perspective
- McCune-Albright syndrome was first discovered by physicians Donovan McCune and Fuller Albright in 1937.
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.
- 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.
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
- The prevalence of McCune-Albright syndrome is between 1:100,000 and 1:1,000,000 making it very rare.
Age
- McCune-Albright syndrome is more commonly observed among infants and young children.
Gender
- McCune-Albright syndrome affects boys and girls equally. [2]
Race
- There is no racial predilection for McCune-Albright syndrome.
Risk Factors
There are no risk factors for McCune-Albright syndrome.
Natural History, Complications and Prognosis
- Early clinical features include café-au-lait macules often shortly after or at birth.
- 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.
- Patients who present with monostotic fibrous dysplasia are required to have evidence of the pathogenic GNAS gene my molecular testing [2]
Symptoms
 |
- Symptoms of McCune-Albright syndrome include the following:
- Precocious puberty
- Fibrous dysplasia leading to pathologic fractures or pain [1] because of fibrous tissue replacing the normal bone [2]
- This can be either monostotic (involving one bone) or polyostotic (involving multiple bones) [2]
- Café au lait spots with “coast of Maine” irregular borders [1] and are often the first presenting sign [2]
- Possible hyperthyroidism, Cushing syndrome, acromegaly or prolactin secretion due to increased thyroid, cortisol, growth hormone or prolactin secretion respectively depending on which tissues are affected [1]
- Phosphate wasting with or without hypophosphatemia [2] mediated by Fibroblast growth factor 23 (FGF23) [2]
Physical Examination
- Patients with McCune-Albright syndrome usually present with bone pain or limping.
- Physical examination may be remarkable for:
- Facial asymmetry due to craniofacial fibrous dysplasia
- Hearing impairment or visual disturbances due to craniofacial fibrous dysplasia
- Café au lait macules
- Goiter due to hyperthyroidism
- Macrocephaly due to excess growth hormone
- Vaginal bleeding in females due to ovarian cysts
- Pubic and or axillary hair and penile enlargement in males
- Growth acceleration in both genders
- Cushingoid features due to hypercortisolism
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. [1]
Electrocardiogram
There are no ECG findings associated with McCune-Albright syndrome.
X-ray
The fibrous dysplasia of bone is present at multiple sites (polyostotic) and xrays would give a ground glass appearance. [3]
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
There are no MRI findings associated with McCune-Albright syndrome.
Other Imaging Findings
There are no other imaging findings associated with McCune-Albright syndrome.
Other Diagnostic Studies
- McCune Albright may be diagnosed using total body bone scintigraphy to identify the fibrous dysplastic lesions. This should then be followed up with radiographs and CT to clearly determine the extent of the lesions. [2]
- It is helpful to perform baseline ophthalmic and audiologic testing for those patients whose fibrous dysplastic lesions involve the craniofacial area [2]
Treatment
Medical Therapy
- The treatment for McCune Albright syndrome includes:
- Precocious puberty- treatment is aimed to prevent bone age advancement [2]
- Fibrous dysplasia – treatment is aimed to minimize morbidity related to pain and fractures: [2]
- Endocrinopathies
Surgery
- Surgery should be used in extreme caution for female patients with ovarian cysts because of the high risk of recurrence and resultant decrease in ovarian reserve. [2]
- Patients with hyperthyroidism are preferred to have a thyroidectomy with total gland resection [2]
Prevention
- Once diagnosed patients with McCune-Albright syndrome are followed-up with:
- Females – early breast cancer screening [2]
- Males – testicular lesions by physical examination and US [2]
- Both genders – signs of precocious puberty, growth hormone excess or growth acceleration (IGF-1 levels), monitoring thyroid function (TSH, free T4, and T3), routine radiographs for fibrous dysplasia lesions particularly to check for scoliosis, serum phosphorous to monitor for development of hypophosphatemia [2] and annual vision and hearing testing to monitor fibrotic lesions affecting these areas. [1]
- Parents should be counseled that McCune-Albright syndrome is not inherited [2]
- There is an increased risk for malignancies and it is advised to minimize radiation exposure and monitor patients regularly. [2]
- Patients should also be advised to avoid contact sports and optic nerve decompressions [2]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 "StatPearls". 2020. PMID 30725777.
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). "GeneReviews®". PMID 25719192.
- ↑ 3.0 3.1 3.2 3.3 3.4 Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL; et al. (2012). "Medical Genetics Summaries". PMID 28520344.