Marfan Syndrome

Marfan syndrome is a genetic disorder of the connective tissue (the material that holds together the various structures of the body). It affects the formation and functioning of the heart valves, blood vessels, lungs, kidneys, eyes and skeleton.

Externally, Marfan is identified by a set of characteristics, including abnormal height, unusually long fingers, possible curvature of the spine and an off–center lens of the eye. Internally, Marfan syndrome patients have a larger and more fragile aorta, the main artery carrying oxygen–rich blood from the heart to the rest of the body. As a result, patients may develop a number of heart–related conditions, including an aortic aneurysm, aortic dissection, aortic regurgitation, and/or mitral regurgitation.

Over the last three decades, the average life expectancy of Marfan patients has almost doubled, to just over 61 years of age. This increase is primarily due to better diagnostics and more aggressive management of the condition. Patients with Marfan should stay in close contact with a team of healthcare professionals, including a cardiologist (heart specialist) and an ophthalmologist (eye) surgeon. Certain tests may be performed yearly to make sure the aorta is not weakening. If it is, surgery may be recommended.

Also, Marfan syndrome patients are encouraged to speak with a physician and a genetic counselor before making a decision about whether or not to conceive a pregnancy.

About Marfan syndrome
Marfan syndrome is a genetic disorder of the connective tissue (the material that holds together the various structures of the body). The syndrome affects the formation and functioning of the heart, blood vessels, lungs, kidneys, eyes and skeleton. Named for the French pediatrician who first described it in 1896, Marfan syndrome may affect males or females of any ethnic origin.

The condition is caused by a defect in a gene that controls the production of fibrillin (a protein found in connective tissue), causing the tissue to weaken or stretch. About three quarters of Marfan syndrome cases occur through an autosomal dominant mode of inheritance. This means that only one parent need have Marfan syndrome to pass the disorder on. For example, if one parent (male or female) has Marfan syndrome, there is a 50 percent chance that each pregnancy will produce offspring inheriting the syndrome, and a 75 percent chance if both parents have Marfan syndrome. About one third of Marfan cases arise spontaneously, from two unaffected parents, due to a mutation in either the egg or sperm. These spontaneous cases are typically associated with a more severe form of the syndrome.

The estimated incidence of Marfan syndrome is between 1 in 10,000 and 1 in 20,000. Approximately 40,000 Americans are diagnosed with the condition each year.

Although many cases of Marfan do not exhibit symptoms until later, the form of the disorder that manifests itself during childhood tends to be more severe. Among these children, the aorta, which is responsible for carrying blood from the heart to the rest of the body, may have structural abnormalities. The most common is a dilated aortic root, or an expanded section where the aorta connects to the heart. This condition tends to get worse over time and may result in a number of complications, including:

  • Aortic dissection. A tear in the inner lining of the aorta, which leads to the separation of the inner and outer layers and blood leakage into the space between the layers. Aortic dissection is the most common cause of premature death for patients with Marfan syndrome.
  • Aortic aneurysm. A condition in which part of the wall of the aorta widens until its diameter is more than 1.5 times its normal size. A serious and life–threatening complication of an aneurysm is a sudden aortic rupture that can lead to massive internal bleeding.
  • Aortic regurgitation. A condition in which the aortic valve (located between the left ventricle and the aorta) cannot close properly, allowing blood to leak backward instead of flowing forward.
  • Mitral valve prolapse. A condition in which the flaps of the mitral valve (located between the left atrium and left ventricle) cannot close properly. As a result, blood may leak back through the valve (regurgitation), when it should only move forward.
  • Arrhythmias. Abnormal heart rhythms that could result if other heart conditions are left untreated.

In recent years, physicians have made great strides forward in the treatment of Marfan patients. Although there is no cure for the underlying genetic defect, Marfan patients are closely monitored to see if their condition is deteriorating. If the aorta becomes too enlarged, preventive surgery may be recommended. Other aggressive treatment options have helped to push the average lifespan of Marfan patients over 60 years. Life expectancy is longer among women than men.

Signs and symptoms of Marfan syndrome
Connective tissue plays an important role in fetal development, growth after birth, the cushioning of joints and the passage of light through the eyes. Some patients have symptoms that are so mild that few to no symptoms are noticed. Other patients may experience a wide variety of symptoms, including those of an underlying heart condition (e.g., shortness of breath, irregular pulse, and fatigue). Signs of Marfan syndrome include:

  • Abnormally shaped chest in which the sternum (breast bone) is either indented or protruding. Indented chests also appear more narrow and are found in 85 percent of Marfan patients with abnormally shaped chests.
  • Disproportionate growth, usually, but not always resulting in excessive height. Though not a health hazard in itself, this trait can cause adjustment problems in adolescents because they are unusually tall compared to other children their age. Their stature also makes children with Marfan syndrome appear older and they may be expected to behave more maturely than is appropriate for their age.
  • Narrow face, slender limbs, and elongated fingers or toes. In addition, patients may have flat feet.
  • Aortic root is enlarged or wider at the base of the aorta as it leaves the left ventricle.
  • Nearsightedness is common, and 50 to 65 percent of Marfan patients have ectopia lentis, a condition in which the lens of an eye is off center. In addition, the white of the eye may appear bluish and the cornea may be malformed. Some patients will develop dislocation of the ocular lens (the focusing structure of the eye). In rare cases, the retina (the part of the eye that is sensitive to light) can also become detached, causing a sudden loss of vision that can only be repaired by an ophthalmologist (eye) surgeon.
  • Curvature of the spine (scoliosis) with or without dural ectasia, the enlargement of the membrane that holds spinal fluid around the brain and spinal cord. Symptoms of dural ectasia include severe headaches and radiating pain in the legs or abdomen.
  • Joint laxity (looseness) or contracture (permanent shortening of muscles, tendons, ligaments).

Diagnosis methods for Marfan syndrome
In 1991, scientists identified the altered gene that causes Marfan syndrome. The gene is located on a region of chromosome 15 and known as the fibrillin–1 (FBN–1) gene. Most patients with Marfan exhibit a mutation of this gene. Some, however, do not, and another gene has been implicated in those cases of Marfan.

Although researchers have located the genetic mutation associated with Marfan, there is no screening test that can conclusively diagnose Marfan. This is because the gene involved is also associated with many other inherited disorders of the connective tissue. These include Beals syndrome, Ehlers–Danlos syndrome, Hajdu Cheney syndrome and Stickler syndrome. To complicate matters further, the syndrome manifests itself differently in each patient, meaning that expensive prenatal genetic testing is a poor indicator of the severity of the resulting Marfan syndrome.

Instead of relying on genetic testing, physicians have developed criteria to diagnose Marfan. These criteria rely on the presence of numerous conditions associated with Marfan. Tests that may be used to diagnose the conditions associated with Marfan include:

  • Skeletal exam. A physical examinationof the appearance and shape of the patient's skeletal structure.
  • Auscultation. The physician will also listen to the heart through a stethoscope to detect whether there is a heart murmur.
  • Family medical history. As complete a record as possible of the conditions and diseases of close family members across several generations.
  • Echocardiogram. A sound wave image of the heart that allows physician to see the structure of the heart and aorta. This is the most common test used to track Marfan patients.
  • Slit–lamp exam. An eye exam using a specialized lamp that can detect lens dislocation.
  • CAT scan (computed axial tomography) of the chest to assess the thoracic aorta.

If a patient has no family history (a &first–degree& relative with Marfan syndrome), a positive diagnosis can be made if the patient has a major manifestation of Marfan in two body systems and involvement of a third system with either a major or minor manifestation. However, if the patient has the genetic mutation associated with Marfan, the diagnosis requires one major manifestation and one minor. A first–degree relative refers to one's parent or sibling (or child). When there is an affected first–degree relative, two body systems, including one major system, need to be affected for a Marfan diagnosis.

Because symptoms of the syndrome may not become apparent until adulthood, it is vital that parents with Marfan have their children checked regularly for signs of the disease. In newborn infants, an evaluation would include:

  • Skeletal measurements such as lengths of the total body, upper and lower body, arm span, legs, hands and fingers. The spine is examined for signs of curvature and the joints for signs of laxity or contracture.
  • Eye exam for lens dislocation, abnormal reflexes, or iridonesis (an uneven shimmering of the iris).
  • Cardiovascular exam for heart murmur, mitral valve prolapse and/or aortic regurgitation.
  • An echocardiogram to assess the valves and aortic size.

This newborn evaluation can help to diagnose Marfan early. However, signs and symptoms may develop over time, so periodic re–evaluations are recommended.

Treatment options for Marfan syndrome
There is no cure for Marfan syndrome. Treatment focuses on repairing or lessening its effect on body systems. Careful management by a physician familiar with the syndrome can greatly improve the patient's prognosis and quality of life. The management plan may include:

  • Annual echocardiograms to monitor the size and function of the heart, valves and aorta. If the echocardiogram reveals significant enlargement of the aorta, corrective surgery may be recommended.
  • Regular eye examinations that include the use of a slit–lamp to detect lens dislocation, and prescription for corrective lenses as needed.
  • Periodic chest x-ray to assess heart and aortic size.
  • Periodic CAT scan of the chest, with contrast, to assess the aorta.
  • Medications such as beta-blockersto lower blood pressure and/or heart rate and reduce the strain on the heart and the aorta.
  • Administration of antibioticsprior to any dental, medical or surgical procedure to reduce the risk of infection in Marfan patients who have developed mitral valve prolapse, mitral valve regurgitation (leak) and/or aortic valve regurgitation.

In addition, patients may need to adapt their lifestyles to reduce the stress on the aorta. This may include:

  • Avoiding heavy lifting, contact sports and strenuous exercise.
  • Wearing protective goggles or glasses when working or playing sports (contact sports are not advised).
  • Wearing a medical alert bracelet to provide information about their condition in case of an emergency.

Because of the complexity of Marfan syndrome, patients may need to see a variety of specialists to treat the different components of the syndrome. Careful monitoring is critical for Marfan syndrome patients so that any conditions that develop, such as an aortic aneurysm, can be treated immediately. Research has found that Marfan syndrome patients who need emergency surgery to repair an aortic aneurysm have a mortality risk eight times greater than patients who had the surgical repair done early and electively. Thoracic aortic aneurysms often have no symptoms until they become life–threatening but can be caught early through periodic echocardiograms or, preferably, through a transesophageal echocardiogram (TEE), and CAT scans with contrast of the heart.

Prevention methods for Marfan syndrome
The Marfan syndrome cases that are caused by spontaneous mutation of a gene cannot be prevented. However, about more than 70 percent of Marfan syndrome patients acquire the disease from one or both parents with Marfan syndrome. Aside from the chance of passing on this inherited risk to the child, women with Marfan syndrome need to consider the physical strain that pregnancy and delivery places on the heart. Pregnant women with Marfan syndrome have a higher mortality risk with pregnancy, as well as an increased risk of mitral valve prolapse, aortic dissection, arrhythmia, heart attack (from the blockage of a coronary artery and sudden cardiac death).

The size of the patient's aorta at the time of pregnancy is an important risk indicator. Marfan patients with a normal aorta have a moderate mortality risk, while patients with an abnormal aorta are at high risk. Patients with an aortic diameter less than 4 centimeters (40 millimeters, or about 1.6 inches) generally tolerate pregnancy well. However, there is a 50 percent mortality rate for pregnant women with Marfan syndrome with an aorta diameter greater than 4 centimeters. Marfan patients are advised to assess childbearing risks with a physician and genetic counselor prior to pregnancy.

For more information on Marfan syndrome, contact:
The National Marfan Foundation
22 Manhasset Avenue
Port Washington, NY 11050
800–8 MARFAN

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