GenTAC Alliance

Marfan Syndrome

What is Marfan syndrome?

Marfan syndrome is a genetic disorder that affects the body’s connective tissue. Connective tissue holds all the body’s cells, organs, and tissue together. It also helps the body grow and develop.

Connective tissue is made up of proteins. The genetic defect that causes Marfan syndrome is a mutation in a gene known as FBN1. This gene affects a protein called fibrillin-1. The abnormal fibrillin-1 protein leads to an increase in the activity of a growth factor, called transforming growth factor-beta (TGF-beta), and eventually leads to problems with connective tissue throughout the body. This, in turn, creates the features and medical problems associated with Marfan syndrome. Because connective tissue is found throughout the body, Marfan syndrome can affect many different parts of the body (see below):

Aorta and other blood vessels
Heart and heart valves
Skeleton and joints
Eyes
Lungs
Skin
Tissue surrounding the spinal cord (dura which lines the dural sac)

Some Marfan features can be more dangerous than others. One example is an increase in the size of the aorta, which is the main blood vessel that carries blood away from the heart to the rest of the body. When the aorta expands, it is called an aortic aneurysm. An aortic aneurysm may lead to a tear in the aorta (acute aortic dissection), which is life-threatening. Surgery to replace the enlarged aorta with an artificial graft can prevent aortic dissection. The eyes, mitral valve, skeleton, lungs, skin, nervous system, and the lining of the dural sac may also be affected. Marfan syndrome does not affect intelligence.

How common is Marfan syndrome?

About 1 in 5,000 people have Marfan syndrome, including men and women of all races and ethnic groups. About 3 out of 4 people with Marfan syndrome inherit it, meaning they get the genetic mutation from a parent who has it. But some people with Marfan syndrome are the first in their family to have the condition. When this happens, it is called a spontaneous mutation. If you have Marfan syndrome, each child you have has a 50% chance of also having this condition.

What are the features of Marfan syndrome?

Every person’s experience with Marfan syndrome is slightly different. No one has every feature, and people have different combinations of the features. How serious each feature is can also vary. Importantly, many features change as you get older. Some features of Marfan syndrome are easier to see than others (Figure 1). These include:

Long arms, legs, fingers, and toes (Figure 2, Figure 3)
Tall for family; often tall and lanky (Figure 2)
Curved spine (scoliosis) (Figure 4)
Chest wall sinks in (pectus excavatum) (Figure 5) or sticks out (pectus carinatum)
Flexible joints including the knees, elbows, and fingers
Flat feet
Long, narrow face (Figure 6)
Crowded teeth (Figure 7)
Stretch marks on the skin that are not related to weight gain or loss

Figure 2 - Long arms are often present in Marfan syndrome

This is a photo of a person with long arms who has Marfan syndrome.

Figure 5 - Sunken chest (pectus excavatum) in Marfan syndrome

Figure 3 - Long fingers (which are often hyperflexible) in Marfan syndrome

This is a photo of someone with with Marfan syndrome playing the piano, showing their long fingers.

Figure 6 - Facial features in Marfan syndrome:

Figure 4 - X-ray example of a curved spine (scoliosis)

Figure 7 - Highly-arched and tall palate and crowded teeth in an individual with Marfan syndrome

Other important features of Marfan syndrome involve the eye, heart and heart valves, lungs, and the connective tissue lining (dura) of the spinal cord. To correctly diagnose and evaluate for involvement of the eyes and heart, you will need testing such as a slit-lamp eye examination and an echocardiogram.

Features of Marfan syndrome may affect many organ systems:

Aorta and blood vessels: enlargement (or aneurysm) of the aorta as it exits the heart (aortic root dilation or aneurysm) (Figure 8 and Figure 9)
Heart and heart valves: a floppy mitral valve which may cause regurgitation or “leaking” of the valve during the heart beat (mitral valve prolapse which may lead to mitral valve regurgitation)
Eyes: nearsightedness (myopia); dislocation of the lens (ectopia lentis) (Figure 10); a clouding of the lens at a young age (early-onset cataracts); a separation of the retina from the back of the eye (retinal detachment)
Lungs: abnormal enlargement of the air spaces at the top of the lung, which may lead to a blister (blebs), or larger sacs (bullae). This may lead to a collapsed lung (pneumothorax)
Dural sac: abnormal connective tissue in the outer lining of the spinal cord may lead to a widening of the spinal canal in the lower spine (lumbosacral dural ectasia) (Figure 11)

Figure 9 - Echocardiogram demonstrating an aortic root aneurysm (arrow)

This image shows a photo of a lens dislocation (ectopia lentis) in Marfan syndrome. The suspensory ligament holding the lens in place is stretched.

Figure 10 - Lens dislocation (ectopia lentis) in Marfan syndrome. The suspensory ligament holding the lens in place is stretched (arrow).

This image shows a CT scan demonstrating lumbosacral dural ectasia.

Figure 11 - CT scan demonstrating lumbosacral dural ectasia (arrow)

What kind of testing will I need?

It is important you go to a doctor experienced with Marfan syndrome for a diagnosis. Your doctor will examine many parts of your body as part of a complete physical exam. Your doctor will also ask you questions about your medical and family history. This may include information about any family member who may have Marfan syndrome, an early heart-related or unexplained death, or a history of aortic aneurysm or dissection.

You should also have tests to identify Marfan features that cannot be seen during the physical exam, including:

Echocardiogram: This is an ultrasound test to look at your heart, its valves, and the aorta (Figure 9)
In adults, a CT scan or an MRI of the chest to look at the entire aorta is important after you are diagnosed with Marfan syndrome.
Electrocardiogram (EKG): This test checks your heart rate and heartbeat.
An eye examination, including a slit lamp evaluation to see if the lenses in your eyes are out of place (dislocated). It is important that your doctor looks inside your eye by fully dilating your pupils with eye drops.
Other tests, such as a CT scan (computerized tomography) or MRI (magnetic resonance imaging) of the lower spine may be needed. It can help your doctor see if the sac around your spinal column is enlarged (dural ectasia), which is a spine problem that is very common in people with Marfan syndrome.

Genetic testing may also provide helpful information. If you have a family history of Marfan syndrome, genetic testing can help show which of your family members have Marfan syndrome and need additional care. This is useful in young children who may not yet show signs of Marfan syndrome.

This image shows an example of a genetic pedigree of a family with Marfan. The tree depicts variations of affected males and females within the tree.

Figure 12 - Genetic Pedigree of a Family with Marfan Syndrome

This example (Figure 12) demonstrates that an individual affected by Marfan syndrome (in black) may pass the gene for Marfan syndrome to his or her children. If someone in the family does not have Marfan syndrome (in white), that unaffected individual cannot pass on a trait for Marfan syndrome as he or she does not carry the mutated gene. (See Genetic testing for HTAD link).

Some of the outward features of Marfan syndrome can be found in other disorders related to Marfan syndrome, such as Loeys-Dietz syndrome or isolated thoracic aortic aneurysms. For this reason, genetic testing may be helpful when a diagnosis cannot be determined through an exam, family history, and imaging tests alone or when lens dislocation (ectopia lentis) is not present and features suggesting an alternative diagnosis are present. Knowing the precise diagnosis is critical to the follow up monitoring and treatment plan.

How will I be treated for Marfan syndrome?

While Marfan syndrome cannot be cured, with diagnosis, monitoring and treatment you can live a long, full life. Working with your doctors will help you manage this condition. Everyone with Marfan syndrome is different, depending on how severe or mild their features are.

In general, you can expect some things you need to think about every day, such as medications and some limitations on physical activity and lifestyle. Then, there are routine doctor appointments, which may be yearly or more often, as well as other tests to make sure that your signs and symptoms are not changing. Sometimes, when symptoms progress or the testing shows a change in the condition (such as significant enlargement of the aorta or leaking of the mitral valve), your doctor will recommend surgery. In most cases, you will have time to plan for surgery; in some cases, immediate surgery may be needed.

Understanding how Marfan syndrome is treated will help you. We encourage you to learn as much as you can about the recommended management for Marfan syndrome so you can be prepared.

People with Marfan syndrome are always at risk for growth or enlargement of the aorta. This growth mostly happens closest to the heart and just above the aortic valve, called the aortic root. The size of your aorta is watched by an echocardiogram which is done at least once a year. You may need these tests more often if your aorta is large or getting to the point where doctors think you may need surgery. Some people need yearly CT or MRI scans (see testing section) to follow the aorta.

You may be given medications to slow the rate of aortic growth. These medications include beta blockers (such as atenolol or metoprolol) to lessen the stress on the aortic wall or angiotensin receptor blockers (ARBs such as losartan or irbesartan) which are believed to block the overactive growth factor (TGF-β) in Marfan syndrome. The US Food and Drug Administration (FDA) also recently warned that people with Marfan syndrome and other aortic aneurysm conditions should avoid commonly used antibiotics called fluoroquinolones (includes Avelox, Cipro, Factive, Levaquin, and Ofloxacin). The reason for this recommendation is that recent medical studies have shown that people who have taken a fluoroquinolone are twice as likely to have an aortic aneurysm or dissection than those who have not taken one of these drugs.

Once the aorta reaches 5 cm, aortic root replacement surgery is recommended (Figure 13). This is open heart surgery. Heart surgeons will replace the aortic root with a graft. In this surgery, your own aortic valve may be sewn inside the graft (a valve sparing root replacement) (Figure 14), or you may receive an artificial valve along with the graft (a Bentall procedure) (Figure 15). If you are given a new valve, it will likely be a mechanical valve. A mechanical valve requires treatment with a blood thinner (anticoagulant) called warfarin. In some cases, aortic root replacement surgery is performed when your aortic size is less than 5 cm, like if you have a family history of aortic dissection (when the wall of the aorta tears) or if the aorta is growing very rapidly.

You may experience leaking (regurgitation) of the mitral valve. In Marfan syndrome, it is common for one or both of the mitral valve leaflets to move backwards into the upper chamber of the heart when the heart beats (mitral valve prolapse). This problem may also require heart surgery to correct.

This image shows a CT scan demonstrating an aortic root aneurysm with an arrow measuring 5 centimeters.

Figure 13 - CT scan demonstrating an aortic root aneurysm (arrow) measuring 5 centimeters

Figure 14 - Valve-sparing root replacement procedure. A. aortic root aneurysm (arrow); B. the aneurysm is removed; C. the aortic valve is reimplanted within the surgical graft; D. the graft is sewn to the normal aorta distally (courtesy of Craig Miller, MD)

Figure 15 - Composite aortic valve and root replacement (Bentall procedure). A mechanical aortic valve prosthesis (arrow) is at the proximal end of the graft and the coronary arteries are reattached to the graft (courtesy of Mayo Clinic)

Will I have any limitations on the exercise I can do?

In general, most people living with Marfan syndrome can and should exercise regularly through low-intensity (aerobic), low-impact activities adapted to meet their specific needs (Figure 16).

Nearly every activity can be done at different intensity levels, and no recommendation applies to every case. For example, shooting baskets in the driveway is different from playing a full-court basketball game. Biking ten miles in one hour on a level course is different from doing a triathlon.

This image shows a photograph of a young man with Marfan in a swimming pool.

Figure 16 - Low-intensity, low-impact exercise is usually recommended

You need to discuss physical activities and activity levels with your physician so you can safely exercise. As you get older, you should keep talking with your doctor about exercise as your health may change.

Competitive and contact sports increase your risk of injury. Doctors worry about:
- Increased heart rate and blood pressure can put added stress on the aorta
- Head impact can damage the eyes and may lead to worsening lens dislocation or a retinal detachment
- Stress on the bones and joints can lead to added pain and joint dislocations
- Bruising and internal bleeding due to certain medications (such as blood thinners)

There are several things to consider when deciding if a sport or activity is safe for you:
- Favor non-competitive activity
- Perform activities at a non-strenuous pace
- Choose an activity you enjoy that you can perform 4–5 times per week for 30 minutes at a time
- Stay at an aerobic level of work (a level where you are not breathing hard and you could easily carry on a conversation during the activity)
- Make sure you wear protective gear as appropriate
- Consider traditional yoga for relaxation and stress reduction
- Do not test your limits

When choosing an activity, avoid the three C’s: competition, collision, and contact. Exercises to avoid include:
- Intense isometric exercises (where you contract specific muscles without moving, such as weightlifting, pullups, pushups, planking or wall sits, or those leading to muscle fatigue or straining).
- Contact sports that may involve a blow to the head; this will help you avoid eye injuries
- Exercise to the point of exhaustion where you are not able to catch your breath and are unable to speak

How does Marfan syndrome affect my ability to start a family?

Pregnancy increases stress on the heart and blood vessels. This can be especially dangerous in women with Marfan syndrome. While there is no clear way to know if you can have a low-risk pregnancy, several points should be considered:

You should discuss pregnancy risks with your doctors before considering pregnancy
Even if your aorta is not significantly enlarged, you should be monitored closely during pregnancy and early after delivery
The risk of serious aortic events such as tear (aortic dissection) is higher if the aorta is bigger than 4.0 cm.
You should know the symptoms of acute aortic dissection; during pregnancy, aortic dissection may occur even when the aorta is not enlarged, and can occur several days after delivery

If you have an artificial aortic valve, you should talk to your doctor about the risks of warfarin on the developing fetus. If you have had aortic root surgery, your risks during pregnancy may be lower. However, this does not remove all risk since other parts of the aorta can enlarge and tear (dissect) related to pregnancy.

If you do get pregnant, it will be considered high-risk (a term doctors use).You should be monitored by a cardiologist and a maternal-fetal medicine specialist or high-risk obstetrician during your pregnancy. During pregnancy, your aorta should be evaluated by echocardiography at least every three months. Before getting pregnant, your entire aorta should be scanned with CT/MRI. These tests will give doctors a better picture of your whole aorta.

Delivery should be by the least stressful method possible. We do not yet know whether a controlled vaginal delivery or a Cesarean section (C-section) is less stressful for women with Marfan syndrome. You and your doctors should talk about the best delivery method for you. It is important you work with doctors who are familiar with Marfan syndrome. C-section is not absolutely necessary because of Marfan syndrome, but may be indicated for any of the usual reasons that would apply to any pregnancy. If possible, you may want to try to have children earlier in life and when the aorta is not enlarged.

Certain medications you take cannot be used during pregnancy as they increase the risk of birth defects and fetal loss. These include:

Angiotensin converting enzyme inhibitors (such as enalapril or captopril)
Angiotensin receptor blockers (such as losartan)

The beta blocker metoprolol is low-risk during pregnancy. Atenolol is not recommended during pregnancy. Lower spine (lumbosacral) disease and enlargement of the sac around the spine (dural ectasia) may affect the use of an epidural. Pre-delivery discussion with your doctors is recommended.

In addition to careful assessment of the risk for women contemplating pregnancies, couples in whom the underlying genetic defect is known may consider prenatal or pre-implantation diagnostics.

Prenatal testing
- Prenatal testing is the technique in which early in the pregnancy (11-12w) the presence of the genetic defect is checked by means of a so-called villous sampling in which a piece of placenta (which is of fetal origin) is punctured away. If the result is abnormal, the pregnancy will be interrupted. With this technique, pregnancy occurs naturally but there is a 50% chance that the pregnancy must be interrupted.
Pre-gestational diagnostic
- PGD is an in vitro fertilization technique that allows for testing of the early embryo for the specific genetic mutation that causes Marfan syndrome. Only embryos without the genetic mutation are implanted. With this technique, pregnancy is artificially established with an embryo that does not carry the abnormal FBN1 gene.

In both cases, it is necessary to know the specific mutation in the gene leading to Marfan syndrome as well as having dedicated pre-conception counseling.

What are the signs and symptoms of an acute aortic dissection?

Aortic dissection (a tear in the wall of the aorta) is very dangerous and must be treated as soon as possible (Figure 17, Figure 18).

We think there are probably 5,000-10,000 dissections a year in the United States. However, it is likely that many dissections are reported as a "heart attack" or "sudden death," when the cause is actually a dissection.

If you have Marfan syndrome you are at much greater risk for an aortic dissection than the general population. It is important to know the signs of an aortic dissection and what to do.

Signs and symptoms of acute aortic dissection may include:

Sudden onset, severe or sharp chest, back, neck/head, or abdominal pain
Pain described as “ripping” or “tearing”
Pain radiating (traveling) from the chest to the back, head and neck, abdomen, or legs
Chest pain associated with fainting (syncope)
Acute shortness of breath
Acute stroke symptoms or inability to use an arm or leg
Chest pain and a newly leaking aortic valve
Unexplained pain and the feeling that “something is very wrong” or a “sense of doom”

Chest pain can have many causes, but when you have Marfan syndrome, it is very important to check for aortic dissection. If you have symptoms that could be due to an aortic dissection, call 911 and get to an emergency room right away. Knowing that you have Marfan syndrome will help if you have unexplained chest, back, or abdominal pain.

Since emergency rooms may be very busy and personnel may not know a lot about Marfan syndrome, you should plan to advocate for yourself if you have these symptoms and end up in an ER. Tell the doctors and nurses at the hospital what you know about your condition. By telling your doctors, nurses, and emergency personnel that you have Marfan syndrome and are concerned about the symptoms related to an aortic dissection, you can be more quickly evaluated for the condition.

A medical alert bracelet can raise alert emergency personnel right away that you are at risk for a life-threatening dissection. It is also beneficial to have your medical records quickly available, such as through Backpack Health, an app for your smartphone. The link to your emergency information in your “backpack” can be added to your medical alert jewelry for easy access.

This image shows composite aortic valve and root replacement (Bentall procedure). A mechanical aortic valve prosthesis. The is an arrow pointing at the proximal end of the graft and the coronary arteries are reattached to the graft.

Figure 17. Aortic root aneurysm and aortic dissection. The arrow denotes the tear (dissection) in the dilated aortic root.

(from Setty R, et al. Int J Surg Case Reports: 2018; 63: 113-117.)

This image shows a CT scan of a type A aortic dissection. Arrows point to the tear in the dilated ascending aorta at the top and the descending aorta at the bottom of the image.

Figure 18 - CT scan of a type A aortic dissection. The black arrows point to the tear in the dilated ascending aorta (top) and the descending aorta (bottom).

Where can I learn more about Marfan syndrome?

The Marfan Foundation: www.marfan.org