McCune–Albright syndrome

Not to be confused with Albright's hereditary osteodystrophy.

McCune-Albright syndrome
Classification and external resources
Café-au-lait skin pigmentation. A) A typical lesion on the face, chest, and arm of a 5-year-old girl with McCune-Albright syndrome which demonstrates jagged "coast of Maine" borders, and the tendency for the lesions to both respect the midline and follow the developmental lines of Blaschko. B) Typical lesions that are often found on the nape of the neck and crease of the buttocks are shown (arrows).
ICD-10	Q78.1
ICD-9	756.54
OMIM	174800
DiseasesDB	7880
MedlinePlus	001217
eMedicine	ped/1386
MeSH	D005359

Alternate names

MAS; Albright syndrome; Albright's disease; PFD; POFD; McCune Albright syndrome; Polyostotic fibrous dysplasia

Defintion

McCune–Albright syndrome, or simply Albright syndrome, described in 1937 by Donovan James McCune and Fuller Albright, is a genetic disorder of bones, skin pigmentation and hormonal problems along with premature puberty.

Epidemiology

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.

Presentation

McCune–Albright syndrome is suspected when two of the three following features are present:

• Autonomous endocrine hormone excess, such as in precocious puberty
• Polyostotic fibrous dysplasia
• Unilateral, i.e. one-sided Café-au-lait spots

Within the syndrome there are bone fractures and deformity of the legs, arms and skull, different pigment patches on the skin, and early puberty with increased rate of growth.

Approximately 20-30% of fibrous dysplasias are polyostotic, which means fibrous dysplasia and sclerotic bone are present in multiple sites; two thirds of patients are polyostotic before the age of ten. The disease frequently involves the skull and facial bones, pelvis, spine and shoulder girdle. The sites of involvement are the femur (91%), tibia (81%), pelvis (78%), ribs, skull and facial bones (50%), upper extremities, lumbar spine, clavicle, and cervical spine, in decreasing order of frequency. The craniofacial pattern of the disease occurs in 50% of patients with the polyostotic form of fibrous dysplasia.

Increased production of hormones by glands regulated by the G protein system is due to a mutation in the gene causing continuous activation of stimulatory G protein. This results in the so called "autonomous production" of hormones, including thyroid hormone, cortisol, estrogen and growth hormone. Therefore, hyperthyroidism, Cushing syndrome, precocious puberty in women with premature thelarche (breast growth), premature menarche (beginning of menstrual function), increased speed of growth and growth hormone excess can ensue. Increased serum estrogen concentrations correlate with large ovarian cysts. Ovarian cysts appear and disappear with changing estrogen concentrations, causing menstrual bleeding when estrogen decreases.

McCune–Albright syndrome has different levels of severity. For example, one child with McCune–Albright syndrome may be entirely healthy, with no outward evidence of bone or endocrine problems, enter puberty at close to the normal age, and have no unusual skin pigmentation. Diagnosis may be made only after decades. In other cases, children are diagnosed in early infancy, show obvious bone disease, and obvious increased endocrine secretions from several glands.

Cause

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.

Inheritance

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.

Diagnosis

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.

Treatment

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.

Prognosis

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.

Notable cases

Mauricio Saravia, a Uruguayan artist with the disease

The disease made headlines in December, 2005 when a Haitian teen afflicted with the disease, Marlie Casseus, underwent a 17-hour emergency surgical procedure to remove a 7 kg (16 pound) tumour-like growth of bone from her face. A series of operations at Holtz Children's Hospital in Miami, Florida restored the child's face to a more normal proportion.

See also

• Fibrous dysplasia
• List of cutaneous conditions
• List of radiographic findings associated with cutaneous conditions

External links

• RockYourPaper
• Medterms.com
• GNAS gene
• NORD
• GFMER
• Fibrous Dysplasia Radiology Image Database

Pediatric glossary of terms | Glossary of medical terms | Dictionary of pediatrics

Professions:Medicine | Nursing | Pharmacy | Healthcare science | Dentistry | Allied health professions | Healthcare