McCune-Albright Syndrome

Café-au-lait skin pigmentation. A) A typical lesion on the face, chest, and arm of a 5-year-old girl with McCune-Albright syndrome which demonstrates jagged "coast of Maine" borders, and the tendency for the lesions to both respect the midline and follow the developmental lines of Blashko. B) Typical lesions that are often found on the nape of the neck and crease of the buttocks are shown. Source: Wikimedia Commons; Claudia E Dumitrescu, Michael T Collins. License Agreement.

McCune-Albright syndrome (MAS) is a genetic disease that affects the bones, skin, and endocrine system. Symptoms can range from mild to severe. The syndrome is characterized by the triad of fibrous dysplasia of bone, café-au-lait skin spots, and precocious puberty.

Other Names

• Polyostotic fibrous dysplasia

Signs and Symptoms

Symptoms of McCune-Albright Syndrome may include:

• Irregular, patchy cafe-au-lait spots, especially on the back
• Menarche (first menstruation) at a very early age
• Premature puberty: early breast development (in girls), early pubic and armpit hair development and early testicular development in boys.
• Abnormal bone growth: fibrous dysplasia (scar-like tissue) in the bone that can lead to fractures, deformities, and abnormal X-rays. Abnormal bone growth in the skull can lead to blindness or deafness due to "pinched" nerves. Deformities may appear in the facial bones and cause cosmetic problems.
• Renal (kidney) involvement may be seen in as many as half patients with MAS. ^[1]

Causes

McCune-Albright syndrome is caused by mutations in the GNAS1 gene. It is associated with mosaicism, meaning that the abnormal gene is present in a fraction, but not all, of the patient's cells.

The syndrome is not inherited. The mutation is sporadic (occurs in the womb during fetal development). This mutation is not passed on to any offspring.

Diagnosis

A physical examination may show signs of:

• Cafe-au-lait spots of the skin
• Skeletal abnormalities
• Precocious puberty
• Hyperthyroidism
• Adrenal abnormalities
• Acromegaly

Laboratory tests may show signs of hyperthyroidism, hyperparathyroidism, excess adrenal hormones, or excess blood prolactin or growth hormone.

X-rays may show fibrous dysplasia that affects multiple bones. Magnetic resonance imaging(MRI) of the head may show a type of tumor called an adenoma in the pituitary gland.

Genetic testing is available for the GNAS1 gene.

Treatment

Precocious puberty is usually treated to prevent short stature. Commonly used drugs include: testolactone, letrozole, anastrozole, and tamoxifen for girls and spironolactone and flutamide in boys. ^[1]

Antithyroidal medications, such as propylthiouracil (PTU), and methimazole (Tapazole) are usually effective in controlling hyperthyroidism in MAS. Spontaneous resolution of hyperthyroidism in MAS almost never occurs, so some form of definitive treatment, either in the form of surgery or radiation, is eventually indicated. Periodic ultrasound of the thyroid is usually done to follow any lesions.

Renal involvement, in the form of renal phosphate wasting, is seen in approximately 50% of the patients with MAS. If phosphate wasting occurs, replacement phosphate should be given.

Growth hormone excess is seen in approximately 20% of the patients with MAS. ^[1]. This excess has been shown to be associated with vision and hearing loss, and macrocephaly in patients with MAS. ^[2] Treatment options include medications, surgery, and radiation. Since most of the growth hormone-secreting tumors also secrete prolactin ^[3], dopamine agonists (cabergoline, etc.) are usually necessary, and are effective at normalizing the serum prolactin.

Cushing syndrome is one of the rarest, but most significant, complications of MAS. Adrenalectomy (surgical removal of one or both of the glands) is often the treatment of choice. If the child is too ill, adrenal blockade may provide stabilization of the disease and buy time until a point in time when surgery can be performed. Metyrapone is a medicine that can be used to treat Cushing Syndrome. In MAS, Cushing syndrome is usually accompanied by hyperthyroidism, which, if not treated, can complicate and worsen the disease course.

Chances of Developing McCune-Albright Syndrome

McCune-Albright syndrome is relatively rare with an estimated prevalence between 1/100,000 and 1/1,000,000. ^[1]

Related Problems

Complications of McCune-Albright syndrome may include:

• Repeated episodes of broken bones
• Cosmetic problems resulting from facial bone abnormalities
• Blindness
• Deafness
• Premature puberty leading to short stature
• Osteitis fibrosa cystica (replacement of calcified bone by fibrous tissue)
• Tumors: malignancies are rare (less than 1%) and are usually sarcomas of the bone </ref name=desc>. Other malignancies associated with MAS include: thyroid, testicular and breast cancers.

Clinical Trials

A list of open clinical trials is available at ClinicalTrials.gov: McCune-Albright syndrome trials.

Research

Recent discoveries

• A recently concluded study looked at the effect of pegvisomant (a growth hormone antagonist) on the growth hormone excess associated with McCune-Albright syndrome. Results are pending. ^[4]
• The aromatase inhibitor anastrozole was shown to be ineffective in the treatment of precocious puberty in girls with McCune-Albright syndrome. ^[5]
• The use of testolactone to treat girls with lutenizing hormone-releasing hormone resistant precocious puberty was evaluated in a recent study. ^[6] Results are pending.
• A case report and review of the literature regarding thyroid dysfunction in McCune-Albright syndrome was done. The study found that although many cases were treated with medication, surgery and ablation were the more effective treatments. ^[7]
• The fibrous dysplasia of McCune-Albright syndrome is discussed. ^[8]

Current research

• The use of alendronate to treat the fibrous dysplasia associated with MAS is being studied. ^[9]

Expected Outcome

The life span is relatively normal in McCune-Albright Syndrome.

History

Etymology

The syndrome was named for American endocrinologist Fuller Albright and pediatrician Donovan James McCune who independently described the syndrome in 1937.

Notable Experts

Genetic testing for MAS exists, but is not widely available. Institutions that are able to do genetic testing include ^[1] the Center for Genetic Testing at Saint Francis, and Genome Diagnostics. In addition, the research laboratories of Professors Francis Glorieux, (Shriners Hospital for Children Montreal, Canada), Paolo Bianco (Rome, Italy) and Charles Sultan (Montpellier, France) can perform genetic testing on a research basis.

References

1. ↑ ^{1.0 1.1 1.2 1.3 1.4} Dumitrescu CE, Collins MT. McCune-Albright syndrome. Orphanet J Rare Dis. 2008 May 19;3:12. Abstract | Full Text
2. ↑ Cutler CM, Lee JS, Butman JA, et al. Long-term outcome of optic nerve encasement and optic nerve decompression in patients with fibrous dysplasia: risk factors for blindness and safety of observation. Neurosurgery. 2006 Nov;59(5):1011-7; discussion 1017-8. Abstract
3. ↑ Akintoye SO, Chebli C, Booher S, et al. Characterization of gsp-mediated growth hormone excess in the context of McCune-Albright syndrome. J Clin Endocrinol Metab. 2002 Nov;87(11):5104-12. Abstract | Full Text
4. ↑ ClinicalTrials.gov. A Study of the Effects of Pegvisomant on Growth Hormone Excess in McCune-Albright Syndrome
5. ↑ Mieszczak J, Lowe ES, Plourde P, Eugster EA. The Aromatase Inhibitor Anastrozole Is Ineffective in the Treatment of Precocious Puberty in Girls with McCune-Albright Syndrome. J Clin Endocrinol Metab. 2008 Jul;93(7):2751-4. Epub 2008 Apr 8. Abstract
6. ↑ ClinicalTrials.gov. Testolactone for the Treatment of Girls With LHRH Resistant Precocious Puberty.
7. ↑ Sallum AC, Leonhardt FD, Cervantes O, Abrahão M, Yazaki RK. Hyperthyroidism related to McCune-Albright syndrome: report of two cases and review of the literature. Arq Bras Endocrinol Metabol. 2008 Apr;52(3):556-61. Abstract
8. ↑ Chapurlat RD, Orcel P. Fibrous dysplasia of bone and McCune-Albright syndrome. Best Pract Res Clin Rheumatol. 2008 Mar;22(1):55-69. Abstract
9. ↑ ClinicalTrials.gov. Alendronate to Treat Polyostotic Fibrous Dysplasia and McCune-Albright Syndrome

External Links

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