McCune-Albright syndrome

What causes McCune-Albright syndrome?

McCune-Albright syndrome (MAS) is caused by somatic mutations in the GNAS gene. This gene provides instructions for making part of a protein that influences many cell functions by regulating hormone activity. GNAS mutations that cause MAS result in a protein that causes the enzyme adenylate cyclase to always be "on". This leads to over-production of several hormones, resulting in the signs and symptoms of MAS.

Precocious puberty in McCune-Albright syndrome is gonadotropin-independent. This means that it is not caused by early release of gonadotropins (luteinizing hormone and follicle-stimulating hormone), but, instead, the cause is the early secretion of high levels of sex hormones (male androgens and female estrogens). Precocious puberty caused by this condition is much more common in girls than in boys, resulting from an excess of estrogen produced by cysts in the ovaries.

Other endocrine problems that may also occur in people with McCune-Albright syndrome are hyperthyroidism, acromegaly and Cushing syndrome. The hyperthyroidism in the MAS is caused by an enlarged thyroid gland (goiter) or by thyroid masses called nodules. Acromegaly results from an excess of growth hormone produced by the pituitary gland (a structure at the base of the brain that makes several hormones). Cushing syndrome results from an excess of the hormone cortisol produced by the adrenal glands.

Last updated on 05-01-20

How is McCune-Albright syndrome diagnosed?

The diagnosis of McCune-Albright syndrome (MAS) can be made in people who have two or more of the following typical clinical features of MAS:

  • Café-au-lait skin spots with characteristic features (jagged, irregular borders; distribution respecting the midline of the body; and following the developmental lines of Blaschko)
  • Polyostotic fibrous dysplasia (involving more than one bone) or GNAS mutation-proven monostotic fibrous dysplasia (involving a single bone)
  • Any of the following endocrine abnormalities (each with specific characteristics):
    • gonadotropin-independent precocious puberty
    • testicular lesions
    • thyroid lesions
    • growth hormone excess
    • phosphate wasting
    • neonatal hypercortisolism (Cushing's syndrome)

MAS may be suspected at birth based upon identifying the characteristic cafe- au-lait spots. However, in many cases, it may not be suspected until late infancy or childhood when precocious (very early) puberty develops or when bone deformities become obvious.

In cases when only one bone has fibrous dysplasia and there are not other symptoms genetic testing is needed to establish the diagnosis.

Last updated on 05-01-20

Is McCune-Albright syndrome inherited?

McCune-Albright syndrome (MAS) is not inherited. It is caused by a random, somatic mutation in the GNAS gene. Mutations that cause MAS occur very early in development, after an egg is fertilized (conception). These mutations are not present in the egg or sperm of the parents of affected children. Because these mutations are acquired after conception, some of the body's cells have a normal GNAS gene, while other cells have the mutated gene. This phenomenon is called mosaicism.

Because mutations that cause MAS are acquired, a person with MAS does not pass the disorder on to children.

Last updated on 05-01-20

What is McCune-Albright syndrome?

McCune-Albright syndrome (MAS) is a disorder that affects the skin, skeleton, and certain endocrine organs (hormone-producing tissues). Cafe-au- lait spots of the skin are common and are usually the first apparent sign of MAS. The main skeletal feature is fibrous dysplasia, which ranges in severity and can cause various complications. Early skeletal symptoms may include limping, pain, or fracture. Endocrinous features may include precocious puberty especially in girls (resulting of estrogen excess from ovarian cysts), excess growth hormone; thyroid lesions with possible hyperthyroidism; renal phosphate wasting, and, rarely, Cushing syndrome caused by an excess of the hormone cortisol produced by the adrenal glands, which are small glands located on top of each kidney. MAS is not inherited. MAS is caused by a somatic mutation in a gene called GNAS, which is acquired after an egg is fertilized and only affects some of the body's cells and tissues. Management depends on the symptoms in each person and may include optimizing function related to fractures and deformities; medications; and surgery.

Last updated on 05-01-20

Can McCune-Albright syndrome be found through amniocentesis?

An amniocentesis is a test during pregnancy that removes a small amount of fluid from the sac around the baby (called the amniotic sac) to look for birth defects and chromosome problems. This test usually looks for chromosome problems in the baby including Down syndrome, Trisomy 13, and Trisomy 18. This test also looks for neural tube defects in the fetus such as spina bifida.

An amniocentesis can only be used to diagnose other genetic conditions during pregnancy if a fetus is suspected to have a particular genetic condition, usually based on abnormal ultrasound or family history. Because McCune- Albright syndrome occurs in people without a family history of the condition, an amniocentesis will not detect it. We recommend that you speak with a genetics professional for additional information about testing for this condition.

GeneTests lists the names of laboratories that are performing genetic testing for McCune-Albright syndrome. To view the contact information for the clinical laboratories, conducting testing click here. Please note: Most of the laboratories listed through GeneTests do not accept direct contact from patients and their families; therefore, if you are interested in learning more, you will need to work with a health care provider or a genetics professional.

Last updated on 05-01-20

What is known about fertility and pregnancy risks in women with McCune Albright syndrome?

Although a lot is known about McCune Albright syndrome (MAS) in children, issues arising specifically during adulthood are less well understood. Precocious puberty can lead to abnormal gonad (ovary or testes) function and problems with fertility in adults. Women with MAS are susceptible to developing large ovarian cysts and irregular vaginal bleeding. This can interfere with normal ovulation. Some affected women experience anovulation (when an egg is not released from the ovaries). In most cases, adults with MAS have been able to have children, even if it may take longer than normal to conceive. Endometrial function may be also affected due to elevated progesterone levels throughout the cycle, which may make implantation of an embryo difficult. In some cases, removal of the affected ovary (ovariectomy) may improve endocrine function and the function of the remaining ovary, thus improving fertility.

Reports have shown that during pregnancy in women with MAS, the rate of bone turnover (when the body removes old bone that should then be replaced) is increased compared with unaffected pregnant women, suggesting that pregnancy could induce changes of bone metabolism. Some researchers have suggested there may be an increased risk of tumor development during pregnancy (i.e. an increased risk of fibrous dysplasia developing into osteosarcoma). However, further studies are needed to clarify the relationship between pregnancy and tumor development in women with MAS.

Last updated on 05-01-20

Are there steps we can take now to determine if she does indeed have McCune- Albright syndrome and to what degree she is affected?

McCune-Albright syndrome (MAS) is usually a clinical diagnosis, which means that specific signs and symptoms must be present before the diagnosis can be made. If MAS is suspected, various tests may be considered to look for the presence of additional signs and symptoms that may confirm the diagnosis. Tests that may be considered include:

While genetic testing for MAS is available, the ability to detect a mutation depends on the level of mosaicism in the tissue, and the sensitivity of the technique used. In the absence of the clinical criteria needed for a diagnosis, genetic testing may detect a mutation. However, because of the somatic mosaic nature of the disease (the mutation only being present in some cells and tissues), a negative result from readily available (but unaffected) tissue does not exclude the presence of the mutation elsewhere in the body.

Unfortunately, it is often not possible to determine how severely a person will be affected when a diagnosis is first suspected or confirmed. For this reason, it is important to be aware of the various tissues that can be (or become) involved, and then to screen for involvement.

Last updated on 05-01-20

What is the long-term outlook for people with McCune Albright syndrome?

The long-term outlook (prognosis) for people with McCune-Albright syndrome (MAS) varies depending on the symptoms and severity in each affected person. Medical therapies can improve or control endocrine symptoms in most people with MAS.

Fibrous dysplasia is progressive throughout childhood and adolescence, and typically plateaus in middle and late adulthood. In some people, small amounts of fibrous dysplasia may cause few or no symptoms. In others, extensive bone disease may cause significant problems including loss of mobility, progressive scoliosis, facial deformity, and loss of vision and/or hearing.

Apart from the small proportion of people with increased surgery-related mortality and those who develop cancer, MAS is not associated with a significantly increased risk of death. In general, people with MAS have a normal life span.

Last updated on 05-01-20

How common is McCune-Albright syndrome?

McCune-Albright syndrome (MAS) is estimated to occur in 1 in 100,000 to 1 in 1 million people, making it a very rare disorder.

Last updated on 05-01-20

How might McCune-Albright syndrome be treated?

Management of McCune-Albright syndrome (MAS) is most effective with a multidisciplinary team of specialists including orthopedists and endocrinologists. Although there is no cure for MAS, drug treatments or surgery may help some of the endocrine symptoms, and surgery may help to manage bone problems that cause visual disturbance, severe pain, or severe disfigurement. Generally, treatment depends on what tissues are affected as well as the severity.

Bisphosphonates are frequently used to treat fibrous dysplasia. Strengthening exercises are recommended to help maintain strength around the bones and minimize the risk of fractures.

More detailed information about the management of MAS is available on Medscape Reference's website.

Last updated on 05-01-20

Healthcare Resources

Fibrous Dysplasia Foundation, Inc.

The Fibrous Dysplasia Foundation has a searchable database of clinicians with experience treating fibrous dysplasia, McCune- Albright syndrome and cherubism. Each clinician is individually reviewed by their Medical Advisory Council.

Last updated on 04-27-20

Name: The MAGIC Foundation 4200 Cantera Dr. #106
Warrenville, IL, 60555, United States
Phone: 630-836-8200 Toll Free: 800-362-4423 Fax : 630-836-8181 Email: Url:
Name: Fibrous Dysplasia Foundation, Inc. 2885 Sanford Ave. SW #40754
Grandville, MI, 49418, United States
Email: Url:

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