Marfan's Syndrome

What Is It?

Marfan's syndrome is a genetic (inherited) disorder that affects the body's connective tissue. Connective tissue is the tough, fibrous, elastic tissue that connects one part of the body with another. It is a major part of tendons, ligaments, bones, cartilage and the walls of large blood vessels. In Marfan's syndrome, the body can't produce enough fibrillin, an important building block of connective tissue.

The problem in Marfan's syndrome is caused by a mutation (change) in a gene. Genes are segments of DNA that direct the body to produce proteins. In many families with inherited Marfan's syndrome, the mutation affects the FBN1 gene on chromosome 15, although a second gene on chromosome 5 may be involved in some cases.

Because of the inherited problem producing fibrillin, people with Marfan's syndrome have from many different problems related to weakness in connective tissue. These problems include:

• Reduced vision In about 65% of Marfan's patients, the lens of the eye becomes dislocated because tiny eye ligaments that normally hold the lens in place are weak. This condition is called ectopia lentis. Marfan's syndrome also seems to increase the risk of nearsightedness, cataracts at an unusually early age (age 40 to 50), glaucoma, detached retina and crossed eyes (strabismus).
• Skeletal abnormalities Patients with Marfan's syndrome are typically very tall, with long limbs and long, slender, spiderlike fingers. They also may have severe chest deformities, such as a chest that either is caved in or protrudes in front. Some patients also have scoliosis (curvature of the spine).
• Cardiovascular changes Weakened connective tissue affects the heart and blood vessels of people with Marfan's syndrome. Cardiovascular problems are the major cause of illness and death related to Marfan's syndrome. In people with Marfan's syndrome, connective tissue weakness can cause mitral valve prolapse (a "floppy" mitral valve that doesn't close properly) or mitral valve regurgitation (a severe problem in closing the mitral valve that results in a significant backflow of blood into the left atrium). It also can lead to an abnormal swelling or dilatation (aneurysm) in the heart's main artery, the aorta, typically at the root of the aorta where it leaves the heart. This aneurysm can lead to aortic regurgitation (abnormal backflow of blood when the heart tries to pump blood forward), aortic dissection (a spreading tear in the inner wall of the aorta that causes a separation between the aorta's inner and outer layers) and aortic rupture (a break in the wall of the aorta, with leakage of blood).

Health experts estimate that about 200,000 people in the United States have Marfan's or related syndromes, and the disorder probably affects one out of every 10,000 newborns.

Symptoms

Marfan's syndrome affects each person differently, and the severity of symptoms can vary. People with severe Marfan's syndrome typically have:

• Long, thin extremities, with or without other skeletal changes
• Vision problems, including nearsightedness and ectopia lentis
• Aortic aneurysms

Diagnosis

Your doctor will ask about any family history of Marfan's syndrome, as well as about any family members who are unusually tall and thin, whether or not they have vision problems. Your doctor also may ask about any family history of sudden death resulting from aortic dissection or rupture, especially if this death was attributed to heart problems.

Your doctor may suspect Marfan's syndrome based on this family history, your personal history of ectopia lentis and your physical appearance. The diagnosis can be confirmed if you have a history of ectopia lentis and have an aortic aneurysm visible on echocardiography, a painless test that uses sound waves to outline the structure of the heart and its major vessels. The diagnosis will be even more certain if you have other skeletal abnormalities (chest wall deformities or scoliosis), or heart murmurs due to aortic or mitral valve abnormalities. Genetic testing is also available in selected medical centers to check for specific chromosomal abnormalities related to abnormal fibrillin production.

Expected Duration

Marfan's syndrome is a lifelong illness that is present at birth.

Prevention

There is no way to prevent Marfan's syndrome. Marfan's patients and their relatives may wish to seek genetic counseling to talk about their risk of passing the disorder to their children.

Treatment

There is no medical treatment to reverse the fibrillin abnormality in people with Marfan's syndrome. In the future, research on a strain of mice that are born with similar fibrillin problems may lead to a successful treatment for Marfan's. Until then, doctors try to prevent or delay the aortic changes seen in Marfan's patients by prescribing beta-blockers. These medications, such as propranolol (Inderal), metoprolol (Lopressor) and atenolol (Tenormin), decrease the strain on the aorta's wall by slowing the heart rate and reducing the force of heart contractions, especially during exercise.

If you have Marfan's, your doctor will monitor your heart health carefully with frequent echocardiograms to check for developing problems in the aorta and mitral valve. If a serious problem is found, you may need surgery to replace the aortic valve, mitral valve or part of the aorta. This usually is done if the patient's aortic root has stretched to more than 6 centimeters in diameter or if the thoracic aorta has widened to greater than 5 centimeters in diameter.

You should follow a non-strenuous exercise program that involves non-competitive, non-contact sports (walking, bicycling, jogging), which you can do at your own pace.

If you have Marfan's-related scoliosis of 20 to 40 degrees, you can be treated with a brace and physical therapy. For scoliosis greater that 45 degrees, you will need surgery. You should have an annual eye examination to look for Marfan's-related eye problems. If you have ectopia lentis, you may be able to be treated with special lenses called aphakic lenses and special eye drops to widen the pupil, rather than surgery. If eye surgery is necessary, it should be done in an ophthalmology center that specializes in the treatment of Marfan's syndrome.

When To Call A Professional

Call your doctor whenever you have vision problems. In many Marfan's patients, the eye doctor (ophthalmologist) is the first to suspect Marfan's syndrome based on findings during a vision exam. Also call your doctor if you have chest pain, shortness of breath, especially during exercise, or an irregular pulse.

If you know that you have Marfan's syndrome, call your doctor immediately if you experience severe pain in the front or back of the chest, sudden weakness or tingling in the legs or arms, or an unexplained fever. These may be symptoms of aortic dissection, a medical emergency that can lead to aortic rupture, which is fatal in 90% to 95% of cases.

Prognosis

Despite the high risk for Marfan's-related cardiovascular problems, the average life expectancy of those with Marfan's syndrome is nearly 70 years.

Additional Info

National Organization for Rare Disorders (NORD)

55 Kenosia Ave.

P.O. Box 1968

Danbury, CT 06813-1968

Phone: (203) 744-0100

Toll-Free: (800) 999-6673

TTY: (203) 797-9590

Fax: (203) 798-2291

E-Mail: orphan@rarediseases.org

http://www.rarediseases.org/