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.^[1][2]

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.^[1][12159]

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.^[1]

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.^[1][3]

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

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.^[4] 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.^[4]

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.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.