McCUNE-ALBRIGHT SYNDROME

McCune-Albright Syndrome General Information

McCune-Albright Syndrome is named after the two physicians who first discovered it 50 years ago. They reported a number of children, the majority of which were girls, with some unusual abnormalities: fractures, bone disease, asymmetry, endocrine disease such as menstrual bleeding in early puberty, increased rate of growth. Over the years, scientists have detected the gene defect that causes this syndrome. The defect occurs in the GNAS1 gene which is linked with a G protein. If the G protein of a cell is abnormal, a chain reaction occurs that makes it produce too many hormones. The mutation’s severity depends on the number of cells involved. An interesting fact is that although genetic, the syndrome is not hereditary. It is also very rare, only 158 cases being reported since 1996. Of course, the number probably is underestimated, since only patients with severe symptoms are reported. McCune-Albright has a very broad range of severity, some children being diagnosed in early infancy with a various number of abnormalities of bone and endocrine glands, while others show no signs of skin, endocrine glands or bone malfunctions can even enter puberty at a normal age.

The McCune-Albright Syndrome is a disease that affects the bones, pigmentation of the skin and also causes hormonal problems which sometimes result in premature sexual development. Although the McCune-Albright Syndrome has been studied for more than 50 years it is difficult to predict the severity of the disease a person will go through.  The next paragraph will present the symptoms which occur when a person is infected.

McCUNE-Albright Syndrome Symptoms

The McCune-Albright Syndrome usually shows itself during the first year of a child’s life. Children who have a severe form may suffer from diarrhea and abnormal liver function. The most obvious sign is the appearance of dark colored skin patches. McCune-Albright Syndrome affects the endocrine glands and especially the gonads (ovaries and testis), this resulting in precocious puberty. Girls are mostly affected, in the form of a menstruation like bleeding in young infants. Adults with McCune-Albright Syndrome may develop a tumor in their pituitary gland which results in excessive growth of bones and soft tissue such as hand and feet. The adrenal cortical may also be affected, resulting in excessive levels of cortisol hormone which causes osteoporosis, high blood pressure, poor growth and abdominal obesity. The liver may also be affected in severe cases. McCune-Albright Syndrome also causes polystotic fibrous dysplasia which means that bones are replaced by fibrous tissue, causing abnormal bone growth. Affected individuals may also suffer from deformities and fractures leading to pain and also walking difficulties. During the first years of a child’s life pigmented spots usually appear which, although aesthetically displeasing, do not cause medical problems. The spots in McCune-Albright Syndrome have irregular edges, which may help in establishing the diagnosis. The syndrome may include some complications such as blindness and deafness, rickets, mobility problems and many others. Although the symptoms are various in numbers, a patient is rarely affected by all of them.

McCune-Albright Syndrome Treatment

McCune-Albright Syndrome cannot be cured; individuals who notice the symptoms should immediately contact a doctor who can advise them what treatments they should undergo to relieve those symptoms. All interventions depend on the symptoms and needs of individual patients. Drug therapy and surgical interventions are what the treatment often involves, but it is not a permanent solution. The treatment for the bone disease is the most difficult stage of caring for a child with severe polyostotic fibrous dysplasia. There is no medical or hormonal treatment effective in controlling such symptom, the surgical procedures used to correct fractures and deformities including pinning, grafting and casting. Using computer tomography and surgical intervention the abnormal growth of the cranio-facial bone can be cured. The operation is executed by an interdisciplinary cranio-facial team with help from plastic surgeons, maxillofacial surgeons and neurosurgeons. In severe cases, Extensive surgery may also be performed in severe cases to move or even remove bone fragments.  

An orthopedic surgeon is used to evaluate and treat dysphasic bone lesions in other sections of a patient’s body. Fractures are treated by aligning and keeping the bones in position throughout the whole healing process, but sometimes surgical fixation may also be necessary. For that, orthoses are used. An effective way of treating bone pain is through biphosphonate therapy. Muscle strength is maintained through regular exercise, swimming and cycling being particularly effective workouts.

The primary aims of the medical treatments are achieving normal puberty and also normal stature. The excessive secretion of oestrogen in girls suffering from McCune-Albright Syndrome is reduced through medical therapy, a treatment also used in boys to decrease testosterone production. Owing to the risk of developing testicular cancer, boys and men suffering from the syndrome should, due to the risk of developing testicular cancer, undergo regular testicle ultrasonography to detect early-stage tumor and hopefully treat it. In the case of the excessive growth hormones, therapy may include the surgical removal of the part of the pituitary gland which secrets the hormone and even the use of an artificial analog of the hormone somatostatin, which reduces the number of hormones secreted. The precocious puberty in the syndrome has been very difficult to treat. Even if the cyst or the affected ovary is removed, the cysts usually reappear in the remaining ovary. Researchers are now testing a new treatment involving medication which blocks estrogen synthesis and it has worked in many patients. The Cushing syndrome, which is the enlargement of the adrenal gland, can be treated by removing the gland or by using drugs to block cortisol synthetis. Some children suffering from McCune-Albright Syndrome may have low levels of phosphorus in the blood due to the loss of phosphate in the urine. This may cause rickets, and is treated with supplemental vitamin D and oral phosphates. Due to the genetic nature of the disease and the mutation it produces, researchers could, one day, using a patient’s DNA plan better methods for treating patients with McCune-Albright syndrome.