McCune-Albright syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 4, 2017
StartDiseasesMcCune-Albright syndrome

McCune-Albright syndrome (MAS) is a condition that affects the bones, skin, and certain endocrine organs (hormone-producing tissues). This disorder is the result of a random genetic mutation that occurs shortly after conception. While there is no cure for the condition, symptoms can be managed.


Definition & Facts

MAS is a condition that affects an individual's bones, skin, and endocrine organs. It is estimated that the condition affects between one in 100,000 and one in 1,000,000 individuals worldwide. Though the condition is caused by a genetic mutation, it is not inherited. Rather, MAS results from a random genetic mutation that occurs after conception. 

Symptoms & Complaints

Symptoms of MAS may vary from one individual to another, and they can range in severity from mild to severe. Fibrous dysplasia is a common symptom in individuals affected with McCune-Albright syndrome. Fibrous dysplasia occurs when scar-like (fibrous) tissue replaces bone.

The fibrous tissue weakens the bone, which makes it prone to fractures. Fibrous dysplasia can also cause bone pain, uneven growth, limping (due to uneven growth in the leg bones), scoliosis (curvature of the spine), loss of mobility, and facial deformity.

Fibrous dysplasia lesions may also lead to neurological issues when abnormal tissue development in the brain compress nearby nerves. Specific neurological symptoms are related to the nerve being compressed. For instance, vision problems or hearing problems can occur when the optic nerve or auditory nerves are compressed. Fibrous dysplasia tends to only affect one side of the body. 

Café-au-lait spots are another common symptom of MAS. Café-au-lait spots are light brown patches of skin that have irregular, jagged borders. These patches may be present at birth, or they may develop shortly thereafter. The patches may vary in size and are usually present on only one side of the body. 

MAS also affects certain endocrine organs. Girls with MAS may experience early puberty (precocious puberty) and may begin menstruating by two years of age. Some girls may begin menstruating as early as four to six months of age. Early-onset menstruation is thought to be caused by excess estrogen, possibly produced by ovarian cysts. Precocious puberty is less common in boys with MAS. However, males with MAS often have abnormally large testes

Additionally, the pituitary gland may produce too much growth hormone in individuals with MAS. This can lead to acromegaly. Some common signs of acromegaly include enlarged hands and feet, enlarged facial features, excessive sweating and body odor, muscle weakness and muscle fatigue, enlarged organs, and coarse, oily, thickened skin. 

The thyroid gland may become enlarged (goiter) or develop masses known as nodules in people with MAS. Approximately half of individuals with MAS develop hyperthyroidism, a condition where the thyroid produces too much thyroid hormone. Common symptoms of hyperthryoidism include rapid heartbeat, unexplained weight loss, sweating, high blood pressure, and tremors. Phosphate wasting may also occur where an increase in the production of the hormone FGF23 impairs the kidneys' ability to function.

Though it is rare, some people with McCune-Albright syndrome develop Cushing's disease. Cushing's disease occurs when too much cortisol is produced by the adrenal glands. Common symptoms of the condition include weight gain in the face and upper body, fatigue, fragile skin, and slowed growth.

Individuals with MAS may also experience gastrointestinal problems. An excess of growth hormone as well as precocious puberty may put individuals with MAS at a higher risk of developing cancer. Cancers that have been associated with MAS include breast cancer, bone cancer, thyroid cancer, and testicular cancer.


MAS is the result of a random mutation in the GNAS gene that occurs after conception. The GNAS gene provides instructions for making one part of a protein complex called a G protein. The GNAS gene produces a protein that helps stimulate the activity of an enzyme called adenylate cyclase.

The gene mutation that causes MAS produces a G protein that causes the adenylate cyclase enzyme to be constantly turned on, which leads to the overproduction of several hormones. Since the genetic mutation that causes MAS is random in nature, the mutation cannot be passed from parent to child.

Diagnosis & Tests

MAS may be suspected at birth if an infant has café-au-lait patches on the skin. However, sometimes the condition is not suspected in infants and children until precocious puberty or bone deformities develop. A physician will begin the diagnostic process by doing a thorough physical examination of the patient and taking a complete medical history. A physician may order some tests to confirm his diagnosis of MAS. 

X-rays and bone scans can be utilized to determine the extent and severity of fibrous dysplasia. Bone biopsies can reveal the characteristic changes to bones that occur in people with fibrous dysplasia. Blood tests may also be ordered to check hormone levels, such as estrogen, testosterone, growth hormone, cortisol, and thyroid hormone. 

Treatment & Therapy

Treatment focuses on managing the specific symptoms a patient has. Treatment options may vary from patient to patient based on symptoms, age, the extent of the disease, and the patient's overall health. Drugs known as bisphosphonates, such as alendronate and pamidronate, can be used to treat fibrous dysplasia. While some individuals respond well to these drugs, others don't respond to bisphosphonates or relapse after a period of improvement. For those who relapse with bone pain, a stronger bisphosphonate medication, such as zoledronic acid, may be prescribed. 

Exercises to strengthen the muscles around fibrous dysplasia lesions may help reduce a patient's risk of fractures. Surgery may also be used in the treatment of fibrous dysplasia. Surgery can be used to to correct limb length discrepancy, to prevent fractures, to correct a disfigurement or deformity, or to treat specific complications, such as scoliosis. Surgery may also be used to relieve symptoms caused by fibrous dysplasia lesions, such as compressed nerves or bone pain.

Drugs may be necessary for females who experience progressive precocious puberty. Letrozole, an aromatase inhibitor, has been used to successfully treat precocious puberty in girls with MAS. An excess of growth hormone can be treated using a class of drugs called somatostatins. Somatostatins inhibit the release of growth hormone from the pituitary gland. If treatment with medication is ineffective, surgery to remove the pituitary gland and radiation to destroy the pituitary tissue may be needed. 

Individuals affected with hyperthyroidism are typically treated with thionamides, medications that inhibit the production of thyroid hormone. However, if medication therapy is unsuccessful at treating hyperthyroidism, surgery to remove the thyroid gland may be needed, with thyroid hormone replacement therapy afterward. 

Cushing's disease may resolve on its own without treatment. Medication to inhibit the release of cortisol have been used to treat Cushing's disease and have even been successful in treating severe cases. When medication therapy is unsuccessful, though, surgery to remove the adrenal glands may be recommended. Individuals who have their adrenal glands removed must receive hormone replacement therapy.

Fibrous dysplasia is progressive during childhood and adolescence and usually plateaus in middle or late adulthood. Severe fibrous dysplasia can lead to some serious complications, such as vision and hearing loss, loss of mobility, and progressive scoliosis. Endocrine symptoms can be managed in most individuals with MAS. Most individuals with MAS live a normal lifespan. 

Prevention & Prophylaxis

There is no way to prevent McCune-Albright syndrome. Because the condition is a result of a random genetic mutation, genetic counseling is not beneficial.

McCune-Albright syndrome is a condition caused by a random genetic mutation. The condition affects an individual's skin, bones, and endocrine organs. While there is no cure for the condition, the symptoms of McCune-Albright syndrome can be managed.