Albright syndrome: A genetic disorder of bones, skin pigmentation and hormonal problems with premature sexual development. Also called McCune-Albright syndrome and polyostotic fibrous dysplasia.
In the syndrome, there is bone disease with fractures and deformity of the legs, arms and skull; pigment patches of the skin; and endocrine (hormonal) disease with early puberty (early menstrual bleeding, development of breasts and pubic hair) and an increased rate of growth. The Albright syndrome is usually caused by mosaicism for a mutation in a gene called GNAS1 (Guanine Nucleotide binding protein, Alpha Stimulating activity polypeptide 1).
The syndrome shows a broad spectrum of severity. Sometimes, children are diagnosed in early infancy with obvious bone disease and markedly increased endocrine secretions from several glands. At the opposite end of the spectrum, many children are entirely healthy, and have little or no outward evidence of bone or endocrine involvement. They may enter puberty close to the normal age, and have no unusual skin pigment at all.
The precocious puberty in Albright girls is caused by estrogens which are secreted into the bloodstream by ovarian cysts, which enlarge, and then decrease in size over periods of weeks to days. The cysts can be visualized and measured by ultrasonography, in which sound waves are used to outline the dimensions of the ovaries. The cysts may become quite big, occasionally over 50 cc in volume (about the size of a golf ball). Frequently, menstrual bleeding and breast enlargement accompany the growth of a cyst. In fact, menstrual bleeding under 2 years of age has been the first symptom of Albright syndrome in 85% of patients. Although ovarian cysts and irregular menstrual bleeding may continue into adolescence and adulthood, many adult women with Albright syndrome are fertile, and can bear normal children.
The precocious puberty in Albright syndrome has been difficult to treat. After surgical removal of the cyst or of the entire affected ovary, cysts usually recur in the remaining ovary. A progesterone-like hormone called Provera can be given to suppress the menstrual bleeding, but does not appear to slow the rapid rates of growth and bone development, and may have unwanted effects on adrenal functioning. The synthetic forms of GnRH (Deslorelin, Histerelin, and Lupron) which suppress LH and FSH, and are used to treat the common, gonadotropin-dependent form of precocious puberty, are not effective in most girls with McCune-Albright syndrome.
Some children with Albright syndrome have very low levels of phosphorus in their blood due to excessive losses of phosphate in their urine. This may cause bone changes associated with rickets, and may be treated with oral phosphates and supplemental vitamin D.
The term "polyostotic fibrous dysplasia" means "abnormal fibrous tissue growth in many bones." Normal bone is replaced by irregular masses of fibroblast cells. When this occurs in weight-bearing bones, such as the femur (upper leg bone), limping, deformity, and fractures may occur. In many children, the arms and/or legs are of unequal length, even in the absence of actual fracture. Regions of fibrous dysplasia are also very common in the bones that form the skull and upper jaw. If these areas begin to expand, skull and facial asymmetry may result.
Polyostotic fibrous dysplasia can often be seen in a plain X-ray picture of the skeleton. A more sensitive method of finding lesions is a bone scan, in which a small amount of radioactivity (an isotope of technetium) is injected into a vein, taken up by the abnormal tissues, and detected by a scanner.
Some children may be minimally affected, with no asymmetry, deformity or fracture, and lesions detected only by a bone scan. In a few children, lesions are found only in the base of the skull. By repeating bone scans at intervals of 1 to 2 years, it has been shown that the bone disease in some children may become more extensive over time. Unfortunately, severe bone disease can have permanent effects upon physical appearance and mobility.
There is no known hormonal or medical treatment effective in controlling progressive polyostotic fibrous dysplasia. Surgical procedures to correct fracture and deformity include grafting, pinning, and casting. Skull and jaw changes are often corrected surgically, with great improvement in appearance. Treatment and therapy for this bone disease is usually the most difficult aspect of caring for a child who has severe polyostotic fibrous dysplasia.
The irregular, flat areas of increased skin pigment in Albright syndrome are called "cafe-au-lait" spots because, in children with light complexions, they are the color of coffee with milk. In dark skinned individuals, these spots may be difficult to see. Most children have the pigment from birth, and it almost never becomes more extensive. The pattern of the pigment distribution is unique, often starting or ending abruptly at the midline on the abdomen in front or at the spine in back. Some children have no cafe-au-lait pigment at all; in a few, it is confined to small areas, such as the nape of the neck or crease of the buttocks. There are seldom any medical problems associated with the areas of cafe-au-lait pigment. Some adolescent children may want to use makeup to obscure areas of dark pigment on the face.
There is no way to accurately predict how severe the disease may become in an affected child. There are no reported cases of any parent being affected, and the children of women with Albright syndrome are normal. All races appear to be affected equally.
The mystery of the cause of the Albright syndrome appears to have been solved by the identification of activating mutations in the GNAS1 gene. The activating mutations render the GNAS1 gene functionally constitutive, turning the gene irreversibly on, so it is constantly active. This occurs in a mosaic pattern, in some tissues and not others.
The syndrome was first described independently in the 1930s by the American pediatrician Donovan James McCune (1902-1976) and a team from the Massachusetts General Hospital in Boston led by the great endocrinologist Fuller Albright (1900-1969):
In 1937, McCune-Albright syndrome (MAS) was described as the triad of cafÃ© au lait macules (CALMs), polyostotic fibrous dysplasia (PFD), and endocrine ...
McCune-Albright syndrome in its classic form consists of at least 2 features of the triad of polyostotic fibrous dysplasia, cafÃ© au lait skin pigmentation ...
McCune-Albright syndrome is a disease that affects the bones, skin, and endocrine (hormone) system. It results from a change (or mutation) in a gene that ...
Albright syndrome: A genetic disorder of bones, skin pigmentation and hormonal problems with premature sexual development. Also called McCune-Albright syndrome and ...
McCune-Albright Syndrome information including symptoms, diagnosis, misdiagnosis, treatment, causes, patient stories, videos, forums, prevention, and prognosis.