Overview Of McCune-Albright Syndrome
McCune-Albright Syndrome is a disorder that affects the bones, skin, and several hormone-producing (endocrine) tissues.
People with McCune-Albright syndrome develop areas of abnormal scar-like (fibrous) tissue in their bones, a condition called polyostotic fibrous dysplasia. Polyostotic means the abnormal areas (lesions) may occur in many bones; often they are confined to one side of the body. Replacement of bone with fibrous tissue may lead to fractures, uneven growth, and deformity. When lesions occur in the bones of the skull and jaw it can result in uneven (asymmetric) growth of the face. Asymmetry may also occur in the long bones; uneven growth of leg bones may cause limping. Abnormal curvature of the spine (scoliosis) may also occur. Bone lesions may become cancerous, but this happens in fewer than 1 percent of people with McCune-Albright syndrome.
Commonly Associated With
- Albright syndrome
- Albright’s disease
- Albright’s disease of bone
- Albright’s syndrome
- Albright’s syndrome with precocious puberty
- Albright-McCune-Sternberg syndrome
- Albright-Sternberg syndrome
- Fibrous dysplasia with pigmentary skin changes and precocious puberty
- Osteitis fibrosa disseminata
- Polyostotic fibrous dysplasia
Causes Of McCune-Albright Syndrome
McCune-Albright syndrome is caused by a mutation in the GNAS gene. The GNAS gene provides instructions for making one part of a protein complex called a guanine nucleotide-binding protein, or a G protein.
In a process called signal transduction, G proteins trigger a complex network of signaling pathways that ultimately influence many cell functions by regulating the activity of hormones. The protein produced from the GNAS gene helps stimulate the activity of an enzyme called adenylate cyclase. GNAS gene mutations that cause McCune-Albright syndrome result in a G protein that causes the adenylate cyclase enzyme to be constantly turned on (constitutively activated). Constitutive activation of the adenylate cyclase enzyme leads to over-production of several hormones, resulting in abnormal bone growth and other signs and symptoms of McCune-Albright syndrome.
Symptoms Of McCune-Albright Syndrome
The main symptom of McCune-Albright syndrome is early puberty in girls. Menstrual periods may begin in early childhood, long before the breasts or pubic hair develop (which normally occur first). The average age that symptoms appear is 3 years old. However, puberty and menstrual bleeding have occurred as early as 4 to 6 months in girls.
Early sexual development may also occur in boys, but not as often as in girls.
Other symptoms include:
- Bone fractures
- Deformities of the bones in the face
- Irregular, large patchy café au lait spots
Exams & Tests
A physical examination may show signs of:
- Abnormal bone growth in the skull
- Abnormal heart rhythms (arrhythmias)
- Large cafe-au-lait spots on the skin
- Liver disease, jaundice, fatty liver
- Scar-like tissue in the bone (fibrous dysplasia)
Tests may show:
- Adrenal abnormalities
- High level of parathyroid hormone (hyperparathyroidism)
- High level of thyroid hormone (hyperthyroidism)
- Adrenal hormone abnormalities
- Low level of phosphorous in the blood (hypophosphatemia)
- Ovarian cysts
- Pituitary or thyroid tumors
- Abnormal blood prolactin level
- Abnormal growth hormone level
Other tests that may be done include:
- MRI of the head
- X-rays of the bones
- Genetic testing may be done to confirm the diagnosis.
Treatment Of McCune-Albright Syndrome
There is no specific treatment for McCune-Albright syndrome. Drugs that block estrogen production, such as testolactone, have been tried with some success.
Adrenal abnormalities (such as Cushing syndrome) may be treated with surgery to remove the adrenal glands. Gigantism and pituitary adenoma will need to be treated with medicines that block hormone production, or with surgery.
Bone abnormalities (fibrous dysplasia) are sometimes removed with surgery.
Limit the number of x-rays taken of affected areas of the body.
Lifespan is relatively normal.