Marfan Syndrome: Causes, Symptoms & Treatment

Marfan syndrome is an inherited disease of the connective tissue. Left undiagnosed, Marfan syndrome can cause sudden death and the number of undiagnosed cases is still estimated to be high. The genetic disease is considered incurable, and treatment options are also very limited, always aiming to improve the quality of life of those affected.

What is Marfan syndrome

Marfan syndrome is genetic and statistically occurs in about 1 to 2 individuals worldwide in a collective of 10,000 people. Geographical or gender differences do not exist; this has been clearly demonstrated in studies. It is a so-called autosomal-dominant inheritance, so the probability that a diseased person will inherit the disease is 50 percent. However, Marfan syndrome also occurs as a spontaneous mutation, in which case neither parent has the disease. It is considered certain that a mutation in the gene for fibrillin is the cause of the disease. Fibrillin is found practically everywhere in the organism and is an important building factor of the elastic fibers of the connective tissue. If this basic structure is missing, the effects on the supporting function of the connective tissue are drastic, which becomes apparent in disorders of all organs and organ systems. The disease is named after the Frenchman Antoine Marfan, a pediatrician.

Causes

The genetic causes of Marfan syndrome lie in specific gene segments. Estimates assume that in Germany alone about 8000 people are affected, due to the large number of undiagnosed or misdiagnosed cases, the number of unreported cases is probably high. The cause of the development of Marfan syndrome as a phenotype is a chromosomal aberration and mutation in the so-called gene FBN1, which is localized on the long arm of the 15th chromosome. To date, more than 500 possible mutation types are known, all of which can lead to the phenotype of Marfan syndrome, i.e. to the full clinical picture of the disease. The FBN1 gene is responsible for decoding the microprotein fibrillin, which in turn is an essential component in the microfibrils of the extracellular matrix; the term extracellular matrix refers to all types of connective tissue. Seventy-five percent of cases of Marfan syndrome are familial, with the remainder due to spontaneous mutations.

Symptoms, complaints, and signs

The multiple symptoms of the disease affect every organ and organ system and are therefore very complex. Most commonly affected by changes in connective tissue are the musculoskeletal system, the cardiovascular system, and the eyes. The slender, long physique with conspicuously elongated extremities and fingers, the so-called arachnodactyly, is striking. All large and small joints are often easily overstretched due to the defective function of the connective tissue. The spine of the affected person is deformed and takes on the form of a rounded back or a sloping position, scoliosis. The elbow joint typically exhibits decreased extensibility due to muscle shortening. The heart valves are largely made up of connective tissue and are not properly formed in Marfan syndrome. Patients therefore often also suffer from the consequences of aortic insufficiency or a vascular outpouching of the aorta, aortic aneurysm. Due to the lack of fixation capacity of the connective tissue in the area of the eyes, the affected persons suffer from defective vision, most frequently myopia. This is because the lens of the eye cannot assume its physiological position due to the lack of connective tissue fibers. Other common symptoms of Marfan syndrome are completely underdeveloped muscles, skin stretch marks, and a tendency to what is known as spontaneous pneumothorax. However, visual diagnosis is only an inadequate diagnostic criterion because the degree of expression of the Marfan phenotype can be extremely discrete in appearance.

Diagnosis and disease progression

The suspected diagnosis already results from the clinical appearance, but must always be corroborated by additional examinations. The final diagnosis is made according to the so-called guidelines of gene nosology, a catalog of diagnostic criteria that places a great deal of emphasis on gene diagnostics in addition to physical examination. In addition, gene nosology is intended to ensure differentiation of Marfan syndrome from other similar genetic diseases.In order to comply with all diagnostic criteria, it is recommended to visit a clinic with experience in the field of Marfan syndrome when a suspected diagnosis is made; an inpatient stay of several days will usually be required there to confirm the diagnosis and differential diagnosis.

Complications

Marfan syndrome usually causes the patient to experience various limitations and symptoms that affect every organ. First and foremost, the syndrome has a very negative effect on the circulatory system, so heart problems may also occur. The vision of the affected person is also significantly reduced by Marfan syndrome, and complete blindness of the patient may occur. Not sailing there is also paralysis and other disorders of sensitivity. It is not uncommon for those affected by Marfan syndrome to appear clumsy and to be restricted in their daily lives. Various psychological complaints and moods can also occur. Young people in particular can suffer from severe psychological complaints as a result of blindness. As a rule, no causal treatment of Marfan syndrome is possible. Therefore, treatment is always symptomatic and aims at limiting the symptoms. As a rule, it cannot be universally predicted whether this will result in a positive course of the disease. In most cases, however, vision cannot be restored, so that those affected are dependent on a visual aid in their daily lives.

When should you see a doctor?

In the case of conspicuous and not natural age-related changes in the connective tissue, a doctor should be consulted to clarify the symptoms. If there are peculiarities in the appearance of the skin, irregularities in the shape and color of the skin, and disturbances in the musculoskeletal system, there is cause for concern. Restrictions of mobility, problems of vision or cardiovascular system should be examined and treated. If there is decreased vision, there is cause for concern. Characteristic of Marfan syndrome are nearsightedness as well as irregularities in cardiac activity. In case of rapid exhaustion during physical activities and fatigue, it is advisable to consult a doctor. Sleep disturbances, inner restlessness or psychological irregularities due to the complaints should be discussed with a doctor. People who have a particularly elongated physique should consult a doctor. If unusually long extremities occur in the proportion of the body, this is a sign of an existing disease that should be diagnosed. Overextensibility of joints as well as deformity of various parts of the body are considered to be a cause for concern and should be examined by a doctor. Disorders of the muscular system, inability to fully extend a joint, and problems performing daily tasks should be evaluated by a physician. If skin stretch marks that cannot be explained appear or if there is an accumulation of air in the upper body, a physician is needed.

Treatment and therapy

A causal, i.e., cause-related, therapy for Marfan syndrome is not known; all forms of treatment are therefore symptomatic and aim to improve the quality of life of those affected. Interdisciplinary care is crucial for the success of the therapy, since all organ systems can always be affected to a greater or lesser extent by the health restrictions. Cardiologists, ophthalmologists, orthopedists and physiotherapists are of particular importance in the professional care of patients with Marfan syndrome. The aortic changes must be monitored closely, because at a certain degree of severity there is an indication for surgery or heart valve replacement. With sufficient medical care, not only an acceptable quality of life, but also an almost normal life expectancy can be ensured. In the event of sudden changes in vision, an ophthalmologist should be consulted immediately. Lens removal or fitting with wide-angle special lenses are not uncommon in Marfan patients.

Outlook and prognosis

In Marfan syndrome, the prognosis is unfavorable. Despite all efforts, the hereditary disease cannot be cured. Causal therapy is not possible because intervention in human genetics is not permitted for legal reasons. Doctors and physicians focus on symptomatic treatment.Nevertheless, the therapy options available are not sufficient to achieve complete freedom from symptoms. If the course of the disease is unfavorable, the affected person may die prematurely. Therefore, it is crucial for the further development when a diagnosis is made. In addition to the increased risk for the development of a mental illness, the syndrome often leads to complaints of the cardiovascular system. These can develop into a heart attack and thus a life-threatening condition if conditions are difficult. In addition, patients may experience complete blindness due to Marfan syndrome. As a result, the quality of life of the affected person is enormously impaired for life. If therapy is started early, improvements and thus a more optimistic prognosis can be achieved. Although it is not possible to achieve freedom from symptoms, secondary diseases of the cardiovascular system in particular can be prevented. In addition, positive changes in vision can be achieved if the diagnosis is made at an early stage. The sooner therapy is started, the higher the probability of achieving an average life expectancy.

Prevention

Unfortunately, direct prevention is not possible to date because of heritability. Genetic diagnosis is also impractical to date because of the large number of different mutations of a single gene. The decisive factor in curbing the chronic course of the disease is to diagnose it as early as possible, as early as infancy, with the aid of genetic analyses of the blood. With this early knowledge, those affected can then do a lot themselves to positively influence the course of the disease. This ranges from the appropriate choice of occupation to applications for the determination of a reduction in earning capacity to attendance at lecture events or self-help groups.

Aftercare

Because treatment of Marfan syndrome is relatively complex and lengthy, aftercare focuses on relieving symptoms. Affected individuals should try to build a positive attitude despite the hardships. In this regard, relaxation exercises and meditation can help calm and focus the mind. This is a fundamental prerequisite for lasting good coping with the disease. In most cases, Marfan syndrome is associated with various complaints and complications, which usually have a very negative impact on the quality of life of the affected person and continue to reduce it. There is also no complete cure for the disease, so the patient is always dependent on treatment by a doctor. Since those affected are often no longer able to manage their daily lives on their own and are dependent on the help of other people, this can reduce their self-esteem. Sometimes Marfan syndrome leads to psychological upsets or depression, which is why it can help to clarify this with a psychologist. An accompanying therapy can help to bring the mental balance out of the imbalance and strengthen the well-being.

What you can do yourself

With Marfan syndrome, the most important thing to do is to have regular checkups with a specialist. The condition can cause serious complications if the patient is not closely monitored and symptoms are medically treated. In addition, there are very limited self-help measures available for the genetic disease. Above all, it is important that the child be observed at all times. If noticeable symptoms appear, for example dizziness or palpitations, a doctor must be consulted immediately. Physiotherapeutic treatment can be used to treat the malformations. In addition, those affected should exercise caution in everyday life to avoid serious injuries and fractures. Parents of children with Marfan syndrome should seek assistive devices such as glasses, crutches or a wheelchair at an early stage. Sometimes the home must be adapted for the disabled in order to make everyday life easier for the affected person. Since psychological complaints usually also occur, comprehensive therapeutic counseling is indicated. The affected person learns to accept the disease and its consequences and can work through the fears associated with it. A visit to a self-help group is also an option.