Synonyms in a broader sense
Type 1 fibrillopathy; arachnodactyly syndrome; spider finesse; Achard-Marfan syndrome; MFA Marfan syndrome is a rare, genetic disease of connective tissue with abnormal changes in the heart, vessels, eye and skeleton with the leading symptom of long, narrow or spider limb. The basis of Marfan syndrome is a mutation of the fibrillin 1 gene, which can either be inherited autosomal-dominantly from the parents or can occur as a new mutation in isolated cases. With a prevalence of 1:10.
000 and about 8000 affected people in Germany, the Marfan syndrome can be counted among the rare diseases. Men and women are equally affected, since the disease does not affect the sex chromosomes. The Marfan syndrome got its name from one of its first describers, Antoine Marfan, who in 1896 observed abnormally long and narrow fingers in a little girl.
The connective tissue of the human body is located outside the cells, also known as the extracellular matrix, which is found throughout the body. It is mainly found in bones, cartilage, tendons and blood vessels, but also in all other organ systems, the connective tissue has the task of binding, enveloping and serving as a guiding structure. The connective tissue is composed of proteins (amino acids) and sugar chains (saccharides).
These proteins can combine with the sugar chains to form large aggregates and then form, for example, the collagen fibrils (building blocks of collagen fibers) of bones or hair. The microfibrils of the connective tissue are also such aggregates, which are composed of fibrillin components, other proteins and sugars. These microfibrils are found in most connective tissues and are always found on the surface of elastic fibers, which give the tissues of the skin, for example, their elasticity.
But they also have their tasks in the fibers of cartilage and tendons. Of each of the different fibrillins that form the backbone of the microfibrils, the genetic information needed to produce these proteins is found on different chromosomes. One of the tasks of fibrillin-1 is the formation of microfibrils, but to do this it must have been correctly folded during its production (synthesis) in the cell (fibroblast), i.e. it must have assumed the correct structure.
In the formation of microfibrils, fibrillin requires various helper molecules, which are necessary for stabilization during cross-linking of the fibrils. This includes calcium. It is therefore understandable that the absence of functional microfibrils can lead to dilatation of the aorta (aortic dilatation), as their stabilizing function is lost due to the defect in the fibrillin.
The excessive growth of the limbs is due to the lack of the microfibrils’ regulating function in the longitudinal growth of the tubular bones. The same is true for the zonula fibers of the eye (suspension apparatus of the eye lens), which lose stability immensely and thus lead to “lens flap”. In order to achieve the necessary correct folding of the fibrils and their aggregation, they must be bound to calcium, which protects them from premature degradation.
Often, however, it is precisely the region in the fibrillae that is affected by the mutation responsible for calcium binding. Consequently, the folding can then fail and the microfibrils are exposed to accelerated degradation. In summary, weakened or even missing microfibrils are responsible for the various symptoms of Marfan’s syndrome, which could not be built up properly due to a defective fibrillin gene.
The first step in the therapy of Marfan syndrome is usually an immediate adjustment of lifestyle after diagnosis. Severe injuries such as whiplash (acceleration trauma) or collisions with others, as in basketball, volleyball or soccer, should be avoided if possible in the case of existing Marfan syndrome, as this can increase the risk of splitting the aorta (dissection). This is particularly problematic because many patients with Marfan syndrome have chosen sports such as basketball because of their height.
The same risk is found in sports where the maximum blood pressure values (blood pressure peaks) are elevated, as is the case with bodybuilding, for example.Regular monitoring of the condition of the affected vessels is always indicated in Marfan syndrome. If the diameter of the aorta is less than 40 millimeters, an annual check is sufficient. If there is a risk of rupture of the aorta, surgery is unavoidable.
In cases of urgent desire for children, family history with splitting of the aorta or simultaneous lack of closure of the heart valves (aortic or mitral valve insufficiency), surgery can be performed even if the aorta (aneurysm) is 50 millimeters wide. The mortality rate of the intervention increases from 1% for planned operations to 27% for emergency operations. As a rule, the technique consists in removing the dilated part of the aorta (Bentall’s operation).
In this procedure, the ascending aorta and the aortic valve are replaced by a valve-bearing “composite” prosthesis. A disadvantage of this procedure is the lifelong need to take anticoagulants (anticoagulants). To avoid this, the valve-preserving technique according to David or Yacoub is increasingly used, whereby only the aorta is replaced by a prosthesis.
Often, however, the preserved valve degenerates over the years, making a second operation necessary. If, on the other hand, there is a weakness of the left heart valve (mitral valve insufficiency), it should be replaced by a valve prosthesis in order to prevent further dilatation of the ascending aorta. Here, too, a lifelong inhibition of blood clotting becomes unavoidable.
If a reconstruction of the mitral valve takes place, these drugs can be dispensed with, which is particularly beneficial in young patients. The therapy of lens dislocation usually consists of surgical removal of the lens and the provision of a correspondingly strongly refractive spectacle construction or the removal of the overlong lens fibres while preserving the lens and the light of the eye. However, often a correction of myopia by fitting glasses or contact lenses is also sufficient.
In the area of the skeletal system, the scoliosis of the spine, which occurs in half of the patients, can be helped by a corset, especially in children. The aim is to prevent a deterioration of the bent spine during growth. However, it does not have a permanent straightening effect.
If the scoliosis is above 40 degrees, surgical straightening of the spine by an orthopedic surgeon should be considered in order to prevent lung problems and back pain. In most cases, funnel chest or pigeon chest therapy is only carried out for cosmetic reasons. Only in the rarest of cases is there compression of the lung, heart or aorta which must be surgically corrected.
In the event of a flat foot, insoles and appropriate footwear can alleviate pain and improve walking comfort. Only rarely is surgical reconstruction of the arch of the foot necessary in Marfan syndrome. The protrusion of the acetabulum is only required to be treated in about 5% of affected adults due to hip pain and restricted mobility and is treated with an artificial hip joint.
The prophylactic use of blood pressure-lowering drugs, beta-blockers, to delay dilatation of the aorta has been shown to be effective, especially in younger, non-operated patients with Marfan syndrome. In older patients or patients who have already been treated, no efficacy could be determined. Endocarditis prophylaxis, i.e. antibiotic therapy to prevent inflammation of the inner lining of the heart, must be taken in Marfan patients for all operations or major injuries, as they are particularly susceptible to this due to the damaged vessels and heart valves.
The Marfan syndrome life expectancy is significantly reduced in untreated patients. With optimal therapy, however, up to 60 years of life can be achieved, provided that the disease and its life-threatening complications are diagnosed early. However, prognostic assessment is problematic in patients who do not meet all criteria for disease. Since Marfan syndrome is a phenotypic continuum that can range from neonatal Marfan syndrome with a life expectancy of less than one year to a mild form with no external manifestations and almost no cardiovascular complications, it is often difficult to accurately assess the time course.
