What is McCune Albright Syndrome?
McCune Albright syndrome is a genetic disorder characterized by abnormal deposits of scar-like or fibrous tissue in bones and skin along with defects in endocrine (hormone-secreting) glands of the body.
Cause of McCune Albright syndrome
This disorder is caused by a mutation in the GNAS gene which codes for a guanine nucleotide-binding protein or G protein.
Typically, G proteins activate a cascade of signaling pathways that regulate a variety of cell functions and hormonal activity. The protein product of the GNAS gene stimulates the activity of an enzyme called adenylate cyclase. Mutation in this gene results in McCune Albright syndrome which causes the activity of G protein to be constantly turned on. This causes overproduction of various hormones, ultimately resulting in bone abnormalities and other symptoms and signs of McCune Albright syndrome.
Incidence
It affects 1 in 100,000 or 1 in 1,000,000 people around the globe.
Bone abnormalities
The abnormal scar-like deposits on bones is a medical condition called polyostotic fibrous dysplasia. The replacement of bone with fibrous or scar-like tissue results in
- Uneven bone growth
- Asymmetry in long bones
- Bone fractures
- Bone deformities
- If fibrous tissue replacement occurs in bones of the skull and face, it results in uneven or asymmetric growth of the face.
- Scoliosis (abnormal curvature of the spine) may also occur.
- Limping may occur due to uneven growth of leg bones.
Endocrine abnormalities
- Endocrine problems include early menstrual bleeding in young girls by the age of two years. This is believed to be due to the increased secretion of estrogen by cysts that develop in the ovaries. These girls may reach puberty early (precocious puberty).
- Precocious puberty may occur in boys as well but it is not very common.
- The thyroid gland produces excessive amounts of the thyroid gland resulting in goiter and thyroid gland enlargement.
- Excessive cortisol is secreted from the adrenal glands which can result in Cushing’s syndrome. Cushing’s syndrome causes retarded growth in children, fat deposits in the face and upper body, fatigue, and other health conditions.
- The pituitary gland secretes excessive growth hormone resulting in acromegaly which is characterized by large hands and feet, coarse facial features, and arthritis.
Café-au-lait skin pigmentation
The literal meaning of café-au-lait means “coffee with milk”. Patients suffering from McCune Albright syndrome present with hyper-pigmented skin lesions that range in color from light brown to dark brown. These patches or lesions may be present from birth. The borders are irregular and the spots vary in size. Café-au-lait spots are also seen in neurofibromatosis and tuberous sclerosis.
Diagnosis
- Technetium-99 scintigraphy (nuclear medicine test) to detect fibrous dysplastic lesions.
- CT scan of the skull in case of fibrous dysplasia in the skull or face.
- Regular hearing tests and vision screening tests are recommended.
- Blood tests to check thyroid hormone and insulin-like growth factor-1 levels.
Treatment
Skeletal abnormalities require:
- Surgical management
- Bisphosphonates to relieve pain
- Muscle-strengthening exercises to prevent bone fractures
- Denosumab to prevent tumor growth
Endocrine abnormalities require:
- Aromatase inhibitors to prevent precocious puberty and short stature in girls
- In boys, aromatase inhibitors along with flutamide and spironolactone to treat excess secretion of androgens
- Thioamides for hyperthyroidism
- Somatostatin analogs or pegvisomant for acromegaly
- Adrenalectomy for Cushing syndrome which a rare event
- Calcitriol for hypophosphatemia
