McCune-Albright syndrome

This is part of Rare diseases.

Diagnosis: McCune-Albright syndrome

Synonyms: --


Date of publication: 2010-03-30
Version: 2.0 

ICD 10 code


The disease

McCune-Albright syndrome is a rare disease characterised by abnormalities in skeletal development, distinctive skin pigmentation and an abnormal pattern of hormone production. Many children produce an excess of sex hormones which can result in the premature onset of puberty. The disease was first described in 1936, by the American paediatrician Donovan James McCune and the endocrinologist Fuller Albright.


The exact incidence remains unknown. In Sweden it is estimated that the number of individuals with the syndrome lies at approximately one hundred.


McCune-Albright syndrome is caused by a mutation (structural defect) in a gene known as GNAS1. This gene codes for a signalling protein that stimulates formation of cAMP which, among other things, regulates many of the hormone-producing (endocrine) glands in the body. A GNAS1 mutation causes over-production of hormones. GNAS1 is located on the long arm of chromosome 20 (20q13.2). This cellular mutation occurs very early in the development of the foetus, in the first ten weeks of gestation. All cells descended from the mutated cell are affected, and small groups are distributed among the healthy cells. This pattern is known as genetic mosaicism. The earlier the mutation occurs in foetal development the more cells are affected, so clinical signs vary greatly between individuals.


The syndrome is caused by a new mutation, meaning that the affected individual is the only member of his or her family to have the syndrome, and that the abnormality in the genetic material is not inherited. There is virtually no increased risk that the parents of a child with a new mutation will have another child with the same disorder. The affected individual will not pass on the mutation as the sex cells (ova and sperm), are usually normal and do not carry the mutation.


The syndrome is characterised by hormonal (endocrine) abnormalities, the presence of patches of darker skin, and a bone disorder where fibrous tissue develops in place of normal bone (fibrous dysplasia).

During their first year, children with severe forms of the syndrome can experience long-lasting bouts of diarrhoea and impaired liver function. In most cases, however, the syndrome is not diagnosed until distinctive patches of pigmented skin become apparent. The distribution of these patches may vary widely and, unlike the café-au-lait spots associated with other conditions, they are irregular in shape.

Endocrine disorders

The most common endocrine disorder associated with McCune-Albright syndrome affects the gonads (the ovaries or testes). The ovaries produce oestrogen and the testes produce testosterone. Overproduction of these sex hormones results in precocious puberty. This condition is more common in girls, and may cause menstruation-like bleeding in female infants. In McCune-Albright syndrome this bleeding may occur before breasts start to develop, which is not the case in other forms of precocious puberty. In boys, one or both testicles and the penis may increase in size, accompanied by other signs of puberty such as growth of pubic hair, increased perspiration and perspiration odour, and acne. Boys with the syndrome have a slightly increased risk of developing testicular cancer in adulthood. Precocious puberty is associated with an early growth spurt, but growth subsequently ceases and adults with the syndrome are usually of short stature. If skeletal abnormalities are extensive the individual may be of extremely short stature.

Hyperthyroidism (an over-productive thyroid gland) is common. Symptoms include increased perspiration, weight loss, anxiety, tremors and rapid heartbeat (hypertyreosis).

Adults with the syndrome may develop a benign pituitary tumour which produces growth hormone. This leads to the growth and thickening of certain bones and soft tissues (acromegaly) in, for instance the hands and feet, tongue, chin and brow. A corresponding excess of growth hormone in children leads to gigantism, but is extremely rare. If abnormal cells are found in the adrenal gland, excessive production of the important hormone cortisol may result, leading to abdominal obesity, a rounded face, restricted growth, brittle bones (osteoporosis), muscle weakness, high blood pressure and easy bruising (Cushing syndrome).

McCune-Albright syndrome can also result in an over-production of calcium caused by a tumour in the parathyroid glands. This may result in fatigue, muscle weakness, poor appetite and constipation, but sometimes gives no symptoms at all. Occasionally more serious symptoms arise, such as excessive thirst, increased urine production and kidney stones.

Excessive levels of phosphate may be excreted in urine, in which case bone growth will be impaired.

In severe cases, the liver may also be affected.

Fibrous dysplasia

Individuals with McCune-Albright syndrome have fibrous dysplasia. In cases of fibrous dysplasia, normal bone is replaced by fibrous tissue in some areas of the body. This means that bone growth is abnormal (uneven and accelerated) which in turn may lead to bone deformities and fractures, resulting in pain and walking difficulties. Most individuals with McCune-Albright syndrome have abnormalities in several parts of the skeleton, so are said to have polyostotic fibrous dysplasia.

Most skeletal symptoms present before the age of ten. The femur (thigh bone), the ribs and the cranium are often affected. Scoliosis (abnormal curvature of the spine) is common. Where abnormalities occur in bones which carry the weight of the body, bones can be deformed and fractures occur. Arms and/or legs may also be of differing lengths.

Abnormal cranial or facial bone growth may also occur, causing facial asymmetry. It has been reported that the upper jaw is more frequently affected than the lower, and that an unusually high number of individuals with the syndrome have bite abnormalities. In rare cases, the bones of the skull compress the vestibular, acoustic and optic nerves, causing balance, hearing and vision problems.

Skin changes

Pale brown, widely-spread pigmented patches of skin are usually apparent from birth. Although they may be aesthetically displeasing, they are helpful when diagnosing the syndrome. In McCune-Albright syndrome the spots have irregular edges (they have been said to resemble a map of small islands). In some cases, the pigmented patches are inconspicuous, and are seen only as minor areas of discolouration on the nape of the neck, or above the buttocks.

It is important to remember that all the characteristic symptoms of the syndrome rarely occur in the same individual.


The diagnosis is usually made on the basis of clinical observations, X-ray findings and blood tests to establish hormone levels. For a diagnosis of McCune-Albright syndrome, fibrous dysplasia must be present, in combination with at least one endocrine disorder and/or patches of pigmented skin. It may be difficult to confirm the underlying mutation through DNA analysis as most cells in the body are normal.

Bone abnormalities are visible in routine X-rays, but computer tomography and magnetic resonance imaging are also used, particularly if the bones of the cranium or face are affected. Hearing and vision should also be checked. Tissue analysis (a histological examination) can be used to confirm fibrous dysplasia as the underlying cause of symptoms.

Endocrine disorders are confirmed using blood and urine analyses. The uterus and the ovaries may be examined with the help of an ultrasound scan.


As yet there is no cure for the syndrome. Treatment is directed at relieving symptoms and compensating for physical shortcomings. Treatment often involves drug therapy as well as surgery.

Abnormal cranio-facial bone growth is assessed using computer tomography. Any surgical intervention is carried out by an interdisciplinary cranio-facial team, drawing together the expertise of plastic surgeons, neurosurgeons and maxillofacial surgeons (specialising in the jaw). In severe cases, extensive surgery is performed to remove (osteotomy), or move, bone fragments. The fitting of dental braces might prove necessary. Vision and hearing should be assessed regularly.

Damage to other bones is examined and treated by an orthopaedic surgeon. Most fractures are treated by keeping the damaged bone aligned throughout the healing process, but surgical intervention can prove necessary. Braces (orthoses) may also be used. Biphosphonate therapy has proved to be effective in treating skeletal pain.

Regular exercise is essential for maintaining muscle strength. Activities such as swimming and cycling, which put no pressure on the skeleton, are particularly appropriate forms of training.

In both girls and boys the primary aim of medical treatment is to assist in the regulation of the onset of puberty, and the attainment of normal stature. In cases of precocious puberty in girls, different medications are used to slow the over-production of oestrogen and, on occasion, to reduce the effect of sex hormones on different organs. In boys, special medication can counteract both the production of, and sensitivity to, testosterone (male hormone). It is important that psychological support is available to young people with the syndrome, and their families.

Owing to the increased risk of developing testicular cancer, males with the syndrome should undergo regular ultrasound examinations for early-stage tumour detection and treatment.

The over-production of thyroid hormone (hyperthyroidism) is treated both medically and surgically. Tumours appearing in the pituitary gland, and causing an excess production of growth hormones, are usually removed surgically, although drug therapy is sometimes used. Tumours on the adrenal gland are removed surgically.

It is important that individuals with the syndrome, and their families, are offered psychological support.

Practical advice


National and regional resources in Sweden

Initial investigations can be carried out at paediatric endocrinology units at university hospitals, where expertise on McCune-Albright syndrome is available. An interdisciplinary diagnostic and treatment team (including a paediatric endocrinologist, gynaecologist, geneticist and child psychiatrist) has been set up at the Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Solna, Stockholm, Sweden. Tel: + 46 8 517 700 00. A specialist in paediatric endocrinology should act as coordinator.

The Oral and Maxillofacial Surgery Clinic, Karolinska University Hospital, Solna, SE-171 76 Solna, Sweden. Tel: +46 8 517 70 00.

Resource personnel

Professor emeritus Martin Ritzén, The Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 723 69, email: martin.ritzen@ki.se.

Senior dental surgeon Anders Westermark, The Oral and Maxillofacial Surgery Clinic, Karolinska University Hospital, Solna, SE-171 76 Solna, Sweden. Tel: + 46 8 517 70 00, email: anders.westermark@karolinska.se.

Courses, exchanges of experience, recreation


Organizations for the disabled/patient associations

There is currently no Swedish patient association for McCune-Albright syndrome.

Courses, exchanges of experience for personnel


Research and development (R&D)



Bulakbaþi N, Bozlar U, Karademir I, Kocaoðlu M, Somuncu I. CT and MRI in the evaluation of craniospinal involvement with polyostotic fibrous dysplasia in McCune-Albright syndrome. Diagn Interv Radiol 2008; 14: 177-181. Review.

Chanson P, Salenave S, Orcel P. McCune-Albright syndrome in adulthood. Pediatr Endocrinol Rev 2007; 4 Suppl 4: 453-462. Review.

Chapurlat RD, Meunier PJ. Fibrous dysplasia of bone. Baillieres Best Pract Res Clin Reumatol 2000; 14: 385-398.

Chapurlat RD, Orcel P. Fibrous dysplasia of bone and McCune-Albright syndrome. Best Pract Res Clin Rheumatol 2008; 22: 55-69. Review.

Cohen MM, Howell RE. Etiology of fibrous dysplasia and McCune-Albright syndrome. Int J Oral Maxillofac Surg 1999; 28: 366-371.

Dumitrescu CE, Collins MT. McCune-Albright syndrome. Orphanet J Rare Dis 2008; 3: 12.

Lala R, Matarazzo P, Andreo M, Marzari D, Bellone J, Corrias A et al. Bisphosphonate treatment of bone fibrous dysplasia in McCune-Albrights syndrome. J Pediatr Endocrinol Metab 2006; 19: 583-593.

Mieszczak J, Eugster EA. Treatment of precocious puberty in McCune-Albright syndrome. Pediatr Endocrinol Rev 2007; 4 Suppl 4: 419-422. Review.

Stanton RP, Diamond L. Surgical management of fibrous dysplasia in McCune-Albright syndrome. Pediatr Endocrinol Rev 2007; 4 Suppl 4: 446-452. Review.

Weinstein LS, Liu J, Sakamoto A, Xie T, Chen M. Minireview: GNAS: normal and abnormal functions. Endocrinology 2004; 145: 5459-5464.

Yamamoto T. Clinical approach to clarifying the mechanism of abnormal bone metabolism in McCune-Albright syndrome. J Bone Miner Metab 2006; 24: 7-10.

Database references

OMIM (Online Mendelian Inheritance in Man)
search: McCune-Albright syndrome, MAS

search: McCune-Albright syndrome

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Professor emeritus Martin Ritzén, The Astrid Lindgren Children’s Hospital, Sweden.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2010-03-30
Version: 2.0
Publication date of the Swedish version: 2009-12-16

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden, Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.


About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.