McCune-Albright Syndrome

By | June 8, 2022

McCune -Albright syndrome is a neurocutaneous syndrome characterized by café-au-lait spots and abnormal bone metabolism. The cause of the hereditary disease is a genetic mutation in the GNAS1 gene, which codes for a regulator of cAMP. Treatment focuses on the administration of bisphosphonates.

What is McCune-Albright Syndrome?

The neurocutaneous syndromes are hereditary diseases whose main symptoms are neuroectodermal mesenchymal dysplasia. The disease group includes the classic phakomatoses. Apart from these diseases, a number of syndromes belong to the group that manifest themselves dermally and simultaneously in the central nervous system. McCune-Albright syndrome is also a neurocutaneous syndrome. For what is jaw cyst, please visit

This extremely rare disease is symptomatic of café-au-lait spots associated with disorders of bone metabolism. The American pediatrician Donovan James McCune and the endocrinologist Fuller Albright first described the disease in the 20th century. In the broadest sense, the Austrian pathologist Carl Sternberg is one of the first to describe the disease.

For this reason, the symptom complex is sometimes referred to as McCune-Albright-Sternberg syndrome. Other synonyms are the terms osteitis fibrosa cystica, leontiasis ossea, Weil-Albright syndrome and osteodystrophia fibrosa.


The prevalence of McCune-Albright syndrome is given as between one and nine patients in 1,000,000 people. Girls are affected more often than boys. In the cases documented to date, a familial accumulation has been observed. The syndrome does not appear to occur sporadically. The inheritance is not yet known. The cause of McCune-Albright syndrome appears to be a genetic mutation.

A mutation in the GNAS1 gene was found in half of all patients. This gene encodes certain polypeptides in the DNA and is located on chromosome 20 in gene locus 20q13.2. Among other things, the gene encodes the protein Gs-alpha, which is considered a cAMP-regulating protein. The genetic modification results in a loss of function of the protein and thus results in a lack of regulation.

The change is a postzygotic mutation and for this reason can only be found in the form of a mosaic. The spontaneous mutation of the gene switches on the adenylyl cyclase and consequently increases the cAMP level of the patients. These processes activate control-independent mechanisms of signal transduction. An autonomous control loop is created.

Symptoms, Ailments & Signs

Patients with MAS show isolated symptoms or symptoms in multiple areas of the skeleton. There is often a limp accompanied by pain. Sometimes the disease also manifests itself in the form of pathological fractures. In many cases, the patients suffer from progressive scoliosis.

Vaginal bleeding occurs in women. The mammary glands develop unusually early. In men, there are sometimes enlarged testicles or penises that result in early sexual activity. These symptoms correspond to hyperactive endocrinopathy. Endocrinopathies can also manifest as hyperthyroidism and be associated with the increased release of growth hormones.

In addition to symptoms of Cushing’s syndrome, there is often a loss of phosphate via the kidneys. The syndrome usually manifests itself in the form of café-au-lait spots in newborns. Patients’ skulls are often affected by abnormalities. The same can apply to the entire skeleton. Pseudopubertas praecox including acromegaly or short stature is particularly common. Some of those affected suffer from a progressive deterioration in visual acuity and also develop malignancies over the course of the disease.

Diagnosis & disease progression

The extent of McCune-Albright syndrome depends on the proliferation, migration and viability of the mutated cells. The diagnosis is made by the doctor based on the clinical presentation. X-rays are often enough for a diagnosis. If in doubt, biopsies can take place to confirm the diagnosis. When examining and diagnosing patients, specific tests consider each organ that may be involved in MAS.

To date, no molecular analysis to detect the GNAS mutation is available to confirm the diagnosis. Nevertheless, genetic counseling is recommended. Neurofibromatosis, osteofibrous dysplasia and non-ossifying fibromas must be excluded in the diagnosis. In addition, idiopathic central precocious puberty and ovarian neoplasia must be differentiated from the differential diagnosis. Treatment and prognosis depend on the tissues affected and the severity of involvement.


McCune-Albright syndrome leads to a number of different complaints and symptoms in the patient. In most cases, this syndrome severely limits the individual’s movement, resulting in limping and other movement disorders. Many women also suffer from increased vaginal bleeding and thus pain as a result of the syndrome.

It is not uncommon for this to lead to mood swings and thus to a significantly reduced quality of life for the patient. The skin of those affected shows brown spots, which have a very negative effect on the patient’s aesthetics. This leads to reduced self-esteem and often to a feeling of shame. Likewise, children may be teased or bullied because of the symptoms of McCune-Albright syndrome.

Furthermore, short stature occurs and those affected suffer from visual problems, which can also restrict everyday life. The individual symptoms of McCune-Albright syndrome can be alleviated by various therapies. However, complete healing does not occur. Furthermore, the affected person is also dependent on a high level of sun protection to protect the skin. Life expectancy is usually not affected by the disease.

When should you go to the doctor?

Abnormalities of the skeletal system or mobility disorders must be presented to a doctor. If there are irregularities in the movement sequences, restrictions in joint activity or a discrepancy in locomotion, a doctor is needed. Poor or crooked posture, pain when moving or a hunched posture of the body are signs of an existing health problem. An examination is necessary so that a diagnosis and treatment can take place.

Women with McCune-Albright syndrome often experience involuntary vaginal bleeding. You should seek medical treatment. In addition, they should exercise special care so that no further complications can arise when planning a possible reproduction. Affected boys and men show enlarged external sexual characteristics when the disease occurs. A doctor’s visit is advisable so that the cause can be clarified and no sexual dysfunctions develop. If mental problems occur due to the optical changes in the testicles and penis, a doctor is also needed.

A doctor should be consulted in the event of growth disorders, short stature or any other visual defect. A change in the shape of the head is characteristic of McCune-Albright syndrome. If changes or abnormalities of the general skin appearance occur, the affected person needs a doctor. Spotting or other discoloration of the skin should be presented to a doctor as it is an indication of an existing disease.

Treatment & Therapy

There is currently no causal therapy available for patients with McCune-Albright syndrome. The syndrome is still considered an incurable disease today. A causal therapy will only be available when gene therapy approaches reach the clinical phase. The treatment is mainly symptomatic and also includes regular supportive controls. Consistent avoidance of UV exposure is recommended as a preventive measure in view of the malignancies that may occur.

The same applies to the consistent use of sunscreens. In addition to these preventive steps, some of the patients receive cosmetic care for their hyperpigmentation. The goal of therapy for her fibrous dysplasia is to stabilize it. Conservative drug therapy is recommended for this purpose. Bisphosphonates, for example, are often used.

The MAS-associated endocrinopathies may require surgical intervention. The same also applies to malignancies. In most cases, patients are recommended additional strength exercises that strengthen the muscles in the immediate vicinity of the bones and thus reduce the general risk of fractures. The strength exercises usually take place under the supervision of a physiotherapist. Depending on the respective organ involvement, the treatment steps mentioned can be supplemented by organ-specific treatment measures.

Outlook & Forecast

McCune-Albright syndrome has an unfavorable prognosis. The disease is based on a genetic disposition. So far, there is no treatment option that provides a cure for the health disorder. Scientists are not allowed to alter human genetics. This means that no causal treatment can take place. The legal requirements mean that doctors concentrate on alleviating the existing symptoms during treatment.

Long-term therapy is necessary, since the termination of the measures initiated is associated with a relapse of the symptoms. Medicines are administered so that the organism has enough bisphosphonates available. In addition, the musculoskeletal system of the affected person is supported with physiotherapeutic measures.

Regular check-ups are necessary to document changes in the complexion at an early stage. As soon as abnormalities appear, further treatment measures are necessary. If skin cancer develops, the patient is at risk of premature death.

Further development improves if the person concerned takes preventive measures. Sufficient protection from the effects of light is just as necessary as carrying out the physiotherapeutic exercise units on your own responsibility.

Due to the optical abnormalities of the disease and the impairment of movement processes, an increased risk of secondary diseases is to be expected with this disorder. Emotional stress in everyday life is so strong for some of those affected that subsequent psychological disorders can develop.


The McCune-Albright syndrome cannot yet be successfully prevented because it is a genetically spontaneous mutation. At best, genetic counseling can be helpful in this context.


Because treatment for McCune-Albright syndrome is relatively complex and lengthy, follow-up care focuses on managing the condition safely. Those affected should try to focus on a positive healing process despite the adversity. To build the appropriate attitude, relaxation exercises and meditation can help to calm and focus the irritated mind caused by the rigors of the illness. Meditative exercises can have a positive effect on severe mood swings. If depression or other mental disorders have developed in the affected patient or family environment, this should be discussed with a psychologist. Therapy can help restore mental balance and create a more positive attitude, making it easier to deal with the disease. In this way, the quality of life can be increased despite the circumstances.

You can do that yourself

The individual symptoms of McCune-Albright syndrome can often be relieved by those affected themselves. However, the syndrome must first be clarified and treated by a doctor in order to rule out a severe course and serious complications.

After diagnosis, strict personal hygiene is important to avoid inflammation in the area of ​​bleeding. Women who experience vaginal bleeding should speak to their gynecologist. If growth disorders occur, the affected person or their parents should seek therapeutic help. It is also important to avoid UV radiation, as this can intensify individual symptoms and may also cause long-term damage. Sunscreens and similar products should also be avoided or only used in consultation with the responsible doctor. A healthy lifestyle with a balanced diet, plenty of exercise and avoiding stress is also recommended. This and preventive measures can in many cases avoid serious consequences.

If the self-help measures mentioned have no effect or if new symptoms appear, the doctor must be consulted in any case. In addition to McCune-Albright syndrome, there may be another disease that needs to be clarified and, if necessary, treated.

McCune-Albright Syndrome