Heart-Related Syndromes

Marfan Syndrome

Manifestations, Causes, Diagnosis, Treatment, Prognosis

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What is Marfan syndrome?

Marfan syndrome is a genetic disorder with an incidence rate of 1 per 5,000 individuals that affects the body's connective tissues, or the tissues in between the main cells of each organ of the body.

All organs contain connective tissue, therefore, the manifestations of Marfan syndrome appear in many parts of the body, particularly the heart, skeletal system and eyes. The skin and lungs may also be involved.

The term "syndrome" refers to the collection of physical findings that occur together often enough to provide a recognizable pattern that allows the diagnosis to be made. It was first described in a 6-year-old girl by the French pediatrician, Antoine Marfan, in 1896.

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Manifestations of Marfan syndrome

Cardiac

The heart is affected in nearly 80 percent of patients with this syndrome. The most important finding is enlargement or dilation of the aorta, the main blood vessel that carries blood to the body. The change in connective tissue in individuals with Marfan syndrome allows the first few inches of the aorta (where the vessel attaches to the lower, left chamber of the heart) to stretch and widen. If the aorta stretches and becomes significantly dilated, a tear or rupture of the vessel may result.

Additionally, as the aorta widens, the leaflets of the aortic valve may be stretched to a point where they fail to close completely and will thereby allow blood to leak back into the heart, causing the left ventricle to enlarge. If left untreated, the heart can go into failure. Another valve of the heart that frequently is affected is the mitral valve, which may also leak causing the heart to become large and work harder.

Skeletal

Skeletal involvement is evident in nearly all individuals with Marfan Syndrome. A person with Marfan syndrome will usually be tall, slender and somewhat loose jointed or limber. The arms, legs, fingers and toes may be disproportionately long when compared to the trunk. Scoliosis is common, and the breastbone may be either very prominent or depressed.

Eyes

Lenses in eyes of patients with Marfan syndrome are dislocated (ectopia lentis) in a high percentage of cases. The degree of visual disturbance associated with ectopia lentis may be mild or quite severe. Near-sightedness (myopia) is also common in individuals with Marfan syndrome. In addition, the retina of the eye may become detached and lead to blindness.

Skin

The skin often exhibits stretch marks, known as stria atrophicae. These can occur among individuals who do not have Marfan syndrome, particularly as a result of pregnancy or marked weight gain and loss. However, patients with Marfan syndrome tend to develop stria at an early age and without weight change. These stria commonly appear on the shoulders, hips and lower back.

Lungs

The lungs also need connective tissue to provide stability and elasticity to the tiny air sacs. Although the altered lung elasticity rarely causes any noticeable problems, patients with Marfan syndrome may develop spontaneous collapse (or pneumothorax) of a lung at a rate of about 50 times greater than the general population. This can occur after a minor blow to the chest or without any identified insult.

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Diagnosis and Genetics of Marfan Syndrome

The cause of the Marfan syndrome has been identified. A gene located on chromosome 15 encodes a specialized protein called "fibrillin" that contributes to the production of normally functioning connective tissue in our body. In Marfan syndrome, a mutation of the fibrillin gene is present in the majority of patients (~75%).

Unfortunately, not all patients with Marfan syndrome have the same abnormal genetic protein. There may be slight variations or mutations in the fibrillin gene, which can produce the same findings in all patients. Unrelated patients or families appear to have different mutations in the fibrillin gene.

The diagnostic evaluation for this syndrome should be performed by physicians experienced with the condition. Evaluation includes a detailed family history and physical examination.

Since the syndrome involves many body systems, the syndrome can be divided into major and minor criteria.

Approximately 80 percent of patients with Marfan syndrome will have a positive family history, which is one major criterion of the syndrome. This requires a very specific diagnosis of the syndrome in other family members, not just someone who is unusually tall. In the rest of the patients, the syndrome results from a new mutation not present in other family members.

A second major criterion for diagnosing the syndrome involves the skeletal system. The most consistent and reliable measure is an abnormally low ratio of the upper trunk of the body to the lower extremities. This ratio is generally less than 0.87 in African-Americans and less than 0.92 in Caucasians.

Another abnormal measurement includes the comparison of the arm span to the total height of the individual, where the arm span to height ratio exceeds 1.05. Other features include abnormalities of the sternum (breastbone), joint hyperextensibility, and scoliosis.

A third major criterion for this diagnosis is ocular, or related to the eyes. Virtually all patients with Marfan syndrome have myopia or near-sightedness. About 70 percent of patients have ectopia lentis or dislocated lenses of the eyes. This may be very mild. Hence, determination of this abnormality requires dilation of the pupils and slit lamp examination by an experienced ophthalmologist.

The fourth major criterion is cardiovascular and includes aortic dilation or dissection.

Minor criteria include mitral valve prolapse, spontaneous pneumothorax, stretch marks, or recurrent hernias.

In order for the diagnosis of Marfan syndrome to be made in the first identifiable case of a family, at least two major criteria in different systems and involvement of a third system must be present. If there is a positive family history, a major criterion in one system and involvement of either major or minor criteria in a second system will permit the diagnosis to be made.

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Treatment and Management of Marfan Syndrome

Although there is no "cure" for this condition, effective treatment is available. Management and treatment of the Marfan syndrome are best discussed and understood by directing attention to the affected organ systems.

The Heart and Aorta: Perhaps one of the most well-known and frightening complications of this syndrome is the sudden rupture of the aorta. Therefore, the first line of defense is detection of this abnormality. It can only be accurately diagnosed and monitored through routine imaging techniques.

The most common technique used is echocardiography, which is able to evaluate the size of the aorta, the progression and change in its dimensions, the overall size and function of the heart, and any heart valve involvement. Routine echocardiography for those patients without obvious cardiovascular problems can be performed on a yearly basis. Enlargement of the aorta, particularly significant enlargement, is often monitored every six months to observe sudden increases in the size of the aorta or progressive enlargement, which may require treatment.

If the aortic valve begins to leak or if the aorta begins to enlarge excessively, surgical intervention by repairing or replacing either the valve or the enlarged aorta may be necessary. Presently, Marfan patients are best advised to have this surgical intervention performed in a medical center that has experience with the syndrome. In some instances, magnetic resonance imaging (MRI) may be utilized to diagnose and regularly evaluate the size of the aorta after surgery or a rupture.

In addition to monitoring the size of the aorta once it is enlarged, several important medical recommendations are made. Patients with an enlarged aorta will be advised against participating in any high impact or high isometric or static activities, such as weight lifting, football, basketball, etc. These activities can cause sudden excessive enlargement of the aorta leading to tearing or possible rupture.

In addition, medications, called "beta blockers," will be prescribed to regulate blood pressure and heart rhythm. These medications help blunt the sudden rise in blood pressure and/or heart rate that occur during activities and may prevent further enlargement of the aorta or reduce the aortic size. Stress tests may be ordered to help monitor the effectiveness of these drugs.

There is a trial underway through the Pediatric Heart Network investigating another group of drugs called angiotehsin II receptor blockers. The goal of this project is to evaluate its effect at slowing the rate of aortic root enlargement and the development of related complications. It is also being compared to the widely used Beta-blockers.

Skeletal System: In the skeletal system, severe curvature of the spine and / or deformity of the breast bone (sternum) represent the most serious problems, mostly related to the impact these have on lung function.

These skeletal abnormalities need to be evaluated by general surgeons or orthopedic surgeons who are experienced in the skeletal deformities, since many of the skeletal changes may require specialized surgery to correct them. Various surgical procedures can stabilize the spine if there is significant spinal deformity, and techniques are available to correct severe depression of the breast bone.

The Eyes: The major problem with the eyes is dislocation of the lenses. In most patients, dislocation of the lens is a minor problem. Dislocated lenses often interfere with vision and may require special eyeglasses or contact lenses. On rare occasions the lens may have to be removed. Because of the increased risk of retinal detachments, activities that involve blows to the head such as football, boxing and diving should be avoided.

Other Systems: Because of the risk of lung collapse (pneumothorax), Marfan syndrome patients should not subject themselves to extremes of air pressure or rapid changes in pressure. For example, Marfan syndrome patients should avoid riding in unpressurized aircraft or diving under water more than several feet.

As mentioned above, the stretch marks on the skin do not cause problems and, although they may be of cosmetic concern, cannot be prevented.

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Inheritance of Marfan Syndrome

Marfan syndrome is inherited in an autosomal dominant manner. The term autosomal means that men and women are equally likely to inherit and / or pass on the condition. Dominant conditions typically affect individuals in every generation.

If an individual has an autosomal dominant condition like Marfan syndrome, they have a 50% or 1 in 2 chance of passing the condition on to each of their children. Because of the variable expression of the Marfan gene, it is not possible to predict how severely a child who inherits the gene will be affected.

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Prognosis for Patients with Marfan Syndrome

While Marfan syndrome is a lifelong disorder that is chronic and often progressive, the outlook has improved in recent years. Early diagnosis and advances in medical technology have enhanced the quality of life for people with the Marfan syndrome and lengthened their lifespan.

In addition, early identification of risk factors (such as aortic dilation) allows doctors to intervene and prevent or delay complications. Advances being made by researchers provide hope for the future. With early diagnosis and appropriate management, the life expectancy for someone with Marfan syndrome is similar to that of the average person.

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