What is it?
Marfan 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 syndrome, the body can't produce normal fibrillin, an important building block of connective tissue.
The problem in Marfan 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 syndrome, the mutation affects the FBN1 gene on chromosome 15, although other gene mutations may be involved in some cases.
Because of the inherited problem producing fibrillin, people with Marfan syndrome have from many different problems related to weakness in connective tissue. These problems include:
- Reduced vision — In about 65 percent of people with Marfan syndrome, 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 lentils. Marfan syndrome also seems to increase the risk of myopia (nearsightedness), cataracts at an unusually early age (age 40 to 50), glaucoma, retinal detachment and strabismus.
- Skeletal abnormalities — People with Marfan 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 is either caved in or protrudes in front. Often, the condition causes a curvature of the spine (scoliosis).
- Excessive joint flexibility – People with Marfan syndrome tend to have abnormally flexible joints (hypermobility). This can lead to joint pain and joint dislocations.
- Cardiovascular changes — Weakened connective tissues affect the heart and blood vessels of people with Marfan syndrome. Cardiovascular problems are the major cause of illness and death related to Marfan syndrome.
In people with Marfan 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).
About one in 5,000 people have Marfan syndrome. Most inherit the abnormal gene from a parent. However, about 20% percent of people with Marfan syndrome have what is called a de novo mutation. This means the genetic mutation occurred after conception and was not inherited from a parent.
Marfan syndrome affects each person differently, and the presence and severity of symptoms can vary. Most often, people with Marfan syndrome become aware of the disorder after they find out that someone else in their family has it or because of their appearance. People with Marfan syndrome typically are tall with long, thin extremities, with or without other skeletal changes.
Vision problems, including nearsightedness and ectopia lentis, usually develop. The symptoms, such as chest pain and shortness of breath, can be very dramatic if there is expansion of an aortic aneurysm or heart valve damage.
Your doctor will ask about any family history of Marfan 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.
Your doctor may suspect Marfan syndrome based on this family history and your physical appearance. The diagnosis can be confirmed if you have a history of ectopia lentis and also have a dilated aortic root (the first part of the aorta as it exits the heart) visible on echocardiography. Echocardiography is 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), excessively mobile joints, or heart murmurs due to aortic or mitral valve abnormalities. Genetic testing can check for specific chromosomal abnormalities related to abnormal fibrillin production for those suspected of having the disease or for close relatives of those with the condition. However, the absence of a known mutation associated with the disease does not exclude Marfan syndrome. Similarly, the presence of a mutation associated with the condition does not confirm the diagnosis since some people with these mutations never develop the syndrome and others develop related disorders separate from Marfan syndrome.
Marfan syndrome is a lifelong condition.
There is no way to prevent Marfan syndrome. People with Marfan syndrome and their relatives may wish to seek genetic counseling to talk about their risk of passing the disorder to their children. A person with Marfan syndrome has a 50% risk of passing the abnormal gene to child. Complications of Marfan syndrome may be prevented with proper care; as examples, medications to lower blood pressure may prevent expansion of an aortic aneurysm and surgery to repair an expanding aneurysm may prevent aortic rupture.
There is no medical treatment to reverse the fibrillin abnormality in people with Marfan syndrome. In the future, research on a strain of mice that are born with similar fibrillin problems or advances in gene editing may lead to successful treatments for Marfan syndrome.
Until then, doctors try to prevent or delay the aortic changes seen in people with Marfan syndrome by prescribing medication that decreases the pressure inside the aorta. Your doctor may advise that you take a beta-blocker and/or an angiotensin receptor blocker. Beta blockers, 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. Losartan and other angiotensin receptor blockers help lower blood pressure, which reduces the stress on artery walls.
If you have Marfan syndrome, your doctor will monitor your heart health with periodic 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. Doctors become concerned when the aortic root size measured on an echocardiogram expands over time. Once it reaches 5 centimeters or more, many experts recommend surgery. Some recommend surgery with lesser aortic root enlargement, especially if there is rapid expansion of the aorta over time.
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-related scoliosis of 20 to 40 degrees, you can be treated with a brace and physical therapy. For scoliosis greater than 45 degrees, surgery is often recommended. You should have eye examinations regularly to look for Marfan-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 syndrome.
When to call a professional
Call your doctor whenever you have vision problems. In many people with Marfan syndrome, the eye doctor (ophthalmologist) is the first to suspect the diagnosis 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 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 percent to 95 percent of cases.
Despite the high risk for Marfan-related cardiovascular problems, the average life expectancy of those with Marfan syndrome is nearly 70 years.
The National Marfan Foundation