McCune-Albright syndrome: Albright syndrome

McCune-Albright syndrome is a rare genetic disorder affecting the bones and skin pigmentation. It is also associated with endocrine problems, notably premature sexual development (see entry, Premature Sexual Maturation). In its classic form, McCune-Albright syndrome involves at least two of these features. Life expectancy is near normal.

The hallmark feature of McCune-Albright syndrome is premature puberty in females. Early development of breasts and pubic hair and an increased rate of growth are common. Menstrual periods may begin in early childhood and early menstrual bleeding is caused by estrogens - chemicals secreted into the bloodstream as a result of the formation of ovarian cysts. The cysts and irregular menstrual bleeding may continue into adolescence and adulthood. Many adult women with McCune-Albright syndrome are fertile.

Less commonly early sexual development occurs in males, involving the development of testes, pubic and underarm hair and increased growth rate.

The spectrum of features has broadened to include problems associated with the heart and liver. Individuals can be differently affected by the range and severity of features. Some children may be affected by bone disease in early infancy and have a range of hormonal problems; others may be entirely healthy.

Many individuals with McCune-Albright syndrome have thyroid gland abnormalities including goitre (generalised enlargement) and irregular masses called nodules and cysts. Some individuals show an excessive secretion of pituitary growth hormone which causes the coarsening of facial features, enlargement of hands and feet and arthritis. Less commonly, some affected individuals may have the features of Cushing syndrome/disease.

Individuals with McCune-Albright syndrome also have Polyostotic Fibrous Dysplasia (abnormal fibrous tissue growth in many bones). The severity of the bone disease is very variable and any bone in the body may be affected. When the Polyostotic Fibrous Dysplasia occurs in weight-bearing bones, such as the femur (upper leg bone), limping, bowing, pain and sometimes fractures may result. If the bones that form the upper jaw and skull are affected, deafness or blindness can result from 'pinched nerves' and facial asymmetry. Some children are affected minimally and in others severe bone disease has a permanent effect upon mobility and physical appearance. Hypersecretion from the parathyroid glands (with elevated parathyroid hormone levels and raised serum calcium) may make the bone disease more severe.

Most children with McCune-Albright have café-au-lait spots (irregular, flat areas of increased skin pigment so called because in children with light complexions, they are the colour of coffee with milk). These may be extensive and usually have irregular margins. They are different from the café-au-lait spots seen in Neurofibromatosis. In dark skinned children, these spots may be difficult to see. The skin pigmentation is not present at birth, but usually from about a month to six weeks of age. The pigmentation does not become more extensive with time.

Inheritance patterns
McCune-Albright syndrome is caused by somatic mutations (or changes) in the GNAS1 gene that take place after conception. As these mutations do not take place in the germ cells (egg and sperm), McCune-Albright syndrome is not inherited but sporadic with no other family member, brother or sister likely to be affected.

Prenatal diagnosis
It may sometimes be possible to perform prenatal diagnosis by chorionic villus sampling (CVS) or amniocentesis during pregnancy. Genetic counselling may be helpful for individuals and families affected by this condition.

Medical text written July 2004 by Contact a Family. Approved July 2004 by Dr R Stanhope, Consultant Paediatric Endocrinologist, Great Ormond Street Hospital, London, UK.

There is no support group for McCune-Albright syndrome. Cross referrals to other entries in the Contact a Family Directory are intended to provide relevant support for these particular features of the disorder. Organisations identified in these entries do not provide support specifically for McCune-Albright syndrome. Families can use Contact a Family's Freephone Helpline for advice, information and, where possible, links to other families. Contact a Family's web-based linking service Making Contact.org can be accessed at http://www.makingcontact.org