Marfan syndrome is a condition that affects the connective tissue. Connective tissue holds the body together and provides support to many structures throughout the body. In Marfan syndrome, the connective tissue isn't normal. As a result, many body systems are affected, including the heart, blood vessels, bones, tendons, cartilage, eyes, nervous system, skin and lungs.
Marfan syndrome is caused by a defect in the gene that encodes the structure of fibrillin and the elastic fibers, a major component of connective tissue. This gene is called fibrillin-1 or FBN1.
In most cases, Marfan syndrome is inherited. The pattern is called "autosomal dominant," meaning it occurs equally in men and women and can be inherited from just one parent with Marfan syndrome. Those that have Marfan syndrome, have a 50 % chance of passing along the disorder to each of their children. In rare cases, a new gene defect occurs due to an unknown cause. Marfan syndrome is also referred to as a "variable expression" genetic disorder, in that not everyone with Marfan syndrome has the same symptoms to the same degree.
Marfan syndrome is present at birth. However, it may not be diagnosed until adolescence or young adulthood. Marfan syndrome is fairly common, affecting 1 in 10,000 to 20,000 people. It has been found in people of all races and ethnic backgrounds.
Sometimes Marfan syndrome is so mild, few if any, symptoms occur. In most cases, the disease progresses with age and symptoms of Marfan syndrome become noticeable as changes in connective tissue occur.
On the outside, people with Marfan syndrome are often very tall and thin. Their arms, legs, fingers and toes may seem out of proportion, too long for the rest of their body. Their spine may be curved and their breastbone (sternum) may either stick out or be indented. Their joints may be weak and easily become dislocated. Often, people with Marfan syndrome have a long, narrow face and the roof of the mouth may be higher than normal, causing the teeth to be crowded.
The entire aorta can become dilated and/or dissected.
Mitral Valve Prolapse (MVP):
leaflets become floppy and do not close tightly
On the inside, many changes occur within the body structures due to the abnormal connective tissue. More than half of all people with Marfan syndrome have eye problems including nearsightedness (blurring of objects far away), lens subluxation (lens of the eye moves away from its typical position) or having a difference in the shape of the eye. About 90 % of people with Marfan syndrome develop changes in their heart and blood vessels:
The blood vessels: The walls of the blood vessels, especially the aorta, the major artery that carries blood from the heart to the rest of the body, becomes weak and dilates (stretches). This increases the risk of aortic aneurysm (a bulging out, similar to a balloon), aortic dissection (a tearing or separating of the layers of the aorta) or rupture (bursting), This can result in medical emergency or even death.
The heart: The heart's valves, especially the mitral valve, can be affected by Marfan syndrome. The valve leaflets become floppy and do not close tightly, allowing blood to leak backwards across the valve (mitral valve prolapse, also called MVP).
- Mitral Valve Prolapse increases the workload on the heart and may cause symptoms of shortness of breath, feeling over-tired, or palpitations (fluttering in the chest). The abnormal flow may cause a heart murmur, which can be heard with a stethoscope.
- Over time, the heart muscle may enlarge and weaken, known as cardiomyopathy. It may progress to heart failure.
- Another problem seen in Marfan syndrome is dilation (widening) of the aortic root, the area where the aorta meets the aortic valve. This can cause the aortic valve to become stretched and leak.
- Arrhythmia (abnormal heart rhythm) may occur in some patients. This is often related to MVP.
Other changes: The changes in lung tissue make people with Marfan syndrome at higher risk for asthma, emphysema, bronchitis, pneumonia and collapsed lung. Decreased elasticity of the skin cause stretch marks to occur even without changes in weight.
Marfan syndrome is based on a clinical diagnosis. A multidisciplinary approach is necessary to make the diagnosis because multiple organ systems must be assessed. Members of the team will assess the eyes, heart and blood vessels, spine and skeletal system. A thorough history of symptoms and information about family members that may have had related problems are also necessary. Other tests, such as chest x-ray, electrocardiogram (ECG) and echocardiogram (an imaging procedure that uses high frequency sound waves to produce a moving picture of the heart's valves and chambers) will be used to evaluate changes in the heart and blood vessels, and detect heart rhythm problems.
If sections of the aorta are not able to be visualized through echocardiogram, or a dissection is already suspected, a transesophogeal echo (TEE), MRI, CT scan may be needed.
Often a CT or MRI is also needed to evaluate for something called dural ectasia. Dural ectasia is a bulging of the lining of the spinal column. It often does not cause any symptoms but in some it can be associated with back pain. Dural ectasia is a feature that helps to support the diagnosis of Marfan syndrome but it can also be seen in other connective tissue disorders.
In some situations a blood test can be used to help in the diagnosis of Marfan syndrome. This blood test is highly specialized and looks for changes in FBN1, the gene that is responsible for most cases of Marfan syndrome. Genetic counseling should accompany genetic testing because FBN1 testing is not always straightforward. Click here to learn more about genetic counseling.
What is genetic testing?
Genetic testing is a specialized laboratory test that looks for changes (also called mutations) in a person’s genetic material (DNA, genes or chromosomes) or in the products that the genes make. A gene contains instructions for our bodies. Genes are made up of chemical bases represented by the letters A, T, C and G. Every gene contains thousands of letters. Most times genetic testing is done by taking a blood sample, but sometimes other body samples (like cheek cells or skin) are needed. FBN1 testing is expensive (approximately $2000). It is often covered by insurance but this varies depending on individual insurance policies. We recommend that you check with your insurance company about coverage prior to having testing.
FBN1 is a large gene and mutations can be found throughout the gene. Over 500 different mutations have been identified in FBN1; most mutations are unique to an individual family. Once a mutation is found in one family member, we expect that same mutation to be present in affected family members. In some cases, a change in the genetic code is found that the lab is not able to determine if it actually causes Marfan syndrome. These types of mutations are called variants. When variants are identified, sometimes it is necessary to test other family members (often parents) to try to determine its significance. The lab may also identify changes in the gene called polymorphisms. Polymorphisms are gene changes that are relatively common and are not likely to cause Marfan syndrome.
Who should have genetic testing?
There are numerous reasons that someone should consider genetic testing for Marfan syndrome, these include:
- Someone with a clinical diagnosis who is interested in genetic testing so that other family members can get tested. (Genetic testing should be initiated in someone with Marfan syndrome first and once a mutation is identified other family members can have testing for that mutation at a reduced cost.)
- Someone with a clinical diagnosis who would like to confirm the diagnosis. (It should be noted that not all cases of Marfan syndrome can be confirmed through genetic testing. Therefore, when a person with a diagnosis of Marfan syndrome does not have a mutation in FBN1 it does not mean that he/she does not have Marfan syndrome. It just means that it was not possible to find the genetic reason with current technology.)
- Someone in whom a diagnosis is suspected but clinical evaluation did not establish the diagnosis.
- Someone in whom Marfan syndrome is one of several diagnoses that are being considered.
- Family members of someone with an identified mutation.
Marfan syndrome requires a treatment plan that is individualized to the patient's needs. Some people may not require any treatment, just regular follow-up appointments with their doctor. Others may need medications or surgery. The approach depends on the structures affected and the severity.
Lifestyle issues
- Follow-up: Routine follow-up including cardiovascular, eye, and skeletal exams, especially during the growing years. Your doctors will discuss the frequency of follow-up with you.
- Activity: Activity guidelines vary depending on the extent of the disease and symptoms. Most people with Marfan syndrome can participate in some type of physical and/or recreational activities. Those with dilation of the aorta will be asked to avoid high intensity team sports, contact sports, and isometric exercises (such as weight lifting). Ask your cardiologist about activity guidelines for you.
- Pregnancy: Genetic counseling should be performed prior to pregnancy as Marfan syndrome is an inherited condition. Pregnant women with Marfan syndrome are considered high risk cases. If the aorta is normal size, the risk for dissection is lower, but not absent. Those with even slight enlargement are at higher risk and the stress of pregnancy may cause more rapid dilation. Careful follow-up, with frequent blood pressure checks and monthly echocardiograms is required during pregnancy. If there is rapid enlargement or aortic regurgitation, bed rest may be required. Your doctor will discuss with you the best method of delivery with you.
- Endocarditis prevention: People with Marfan syndrome who have heart or valve involvement or who have had surgery to treat Marfan syndrome, are a increased risk for bacterial endocarditis. This is an infection of the heart valves or tissue which occurs when bacteria enters the blood stream. To prevent this, antibiotics should be given prior to dental or surgical procedures. Check with your doctor about the type and amount of antibiotics you should take. A wallet card may be obtained from the American Heart Association* with specific antibiotic guidelines.
- Emotional considerations : Learning you have a genetic disorder, such as Marfan syndrome, may affect you in many ways. You may feel angry, sad, or scared. This can be related to the knowledge of having a disease, making changes in your lifestyle, and having careful medical follow-up the rest of your life. Or there may be financial concerns. It may be also concerning to think about risk to future children. It is important to seek medical care from a physician who has experience in treating Marfan syndrome. Get accurate information. It may also help to seek genetic counseling to help understand the disease and your risk for passing it on to your children. The National Marfan Foundation can help provide you with information and support. Click here to learn more.*
Medications
Medications are not used to treat Marfan syndrome, however they may be used to prevent or control complications.
The first medication used is called a beta-blocker. These medications decrease the forcefulness of the heartbeat and the pressure within the arteries, thus preventing or slowing the enlargement of the aorta. Beta-blocker therapy should begin at an early age.
In those people who are unable to take beta-blockers due to asthma or side-effects, a calcium channel blocker, such as verapamil, is recommended.
Surgery
Surgery for Marfan syndrome is aimed at preventing aortic dissection or rupture and treating valve problems.
The normal aorta measures about 1 inch (2.54 centimeters). When the aorta diameter is more than approximately 4.7 centimeters (depending on your height), or if the aorta is enlarging at a rapid pace, surgery is recommended. The decision to have surgery is based on size of the aorta, expected normal size of the aorta, rate of aortic growth, age, height, gender and family history of aortic dissection. Surgery involves a replacement of the dilated portion of the aorta with a graft.
A leaky aortic or mitral valve (regurgitation) resulting in changes in the left ventricle (left lower chamber of the heart, heart's major pumping chamber) or heart failure, require surgery to repair or replace the valve. If surgery is performed early in the process, either the aortic valve or mitral valve can be repaired and preserved. Later in the disease process, the valves may have to be replaced if the valves have deteriorated too much.
It is recommended that people with Marfan syndrome undergo surgery by surgeons who are experienced in this type of surgery. Those that undergo surgery, still require lifelong follow-up and preventive measures to prevent future progression of the disease.
Click here for more information about surgery for Marfan syndrome.
A better understanding of Marfan syndrome combined with earlier detection, careful follow-up and safer surgical techniques have resulted in better outcomes for these patients. At one time, the average age of death was 32 years old. Now, people live active, healthy lives well into their 70's, particularly if they are operated on before they develop aortic dissection and have long-term follow-up by an experienced multidisciplinary team.
More information
If you need more information, click here to contact us , chat online with a nurse or call the Heart and Vascular Institute Resource & Information Nurse at 216/445-9288 or toll-free at 866/289-6911. We would be happy to help you.
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Sources:
- Svensson, LG, Crawford ES. Marfan Syndrome and Connective Tissue Diseases, In Cardiovascular and Vascular Disease of the Aorta. pg. 84-104, WB Saunders, 1997. Philadelphia.
- Svensson, LG, Crawford ES, Coselli JS, et.al. Impact of cardiovascular operations and survival in the Marfan patient, Circulation, 1989;80(3Pt1);1233-42.
- Tsipouras P, Silverman DI, Bosner MS, et.al., Longer Lives for Marfan Syndrome Patients, Cardiology Review: Hypertension and Vascular Disease, 13: March 1996, 25-28.
- National Institute of Arthritis and Musculoskeletal and Skin Disease, Questions & Answers About Marfan Syndrome, DN 3/99, AR-06 QA, http://www.niams.nih.gov/*
- National Marfan Foundation, Marfan Syndrome: Cardiac Concerns, Nov. 1997, http://www.marfan.org/*
- American Heart Association*
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