Marfan syndrome

What is Marfan syndrome?

If you have Marfan syndrome, you have a problem with the connective tissue in your body. (Your connective tissue is the tissue that binds, protects and gives strength to other tissues and organs within your body. It also helps move fat and nutrients around your body and can help repair damage to other tissues.) In Marfan syndrome, your connective tissue becomes weak and 'floppy'.

Marfan syndrome can affect the connective tissue in different parts of your body, including your heart, blood vessels, eyes and skeleton.

Marfan syndrome is rare and is thought to affect about 1 in 3,000 to 1 in 5,000 people. It affects males and females equally. It affects people of all ethnicities equally.

It is the most common genetic problem affecting connective tissue. It is an autosomal dominant condition, meaning you only need one parent, not both, to have it to inherit it yourself.

It can also arise "de novo" which means that the gene causing Marfan syndrome has not been inherited but has "mutated" (changed) during the early developments after conception. This is the case in 1 in 4 people with Marfan syndrome who will, therefore, not have a parent who is affected.

Marfan syndrome symptoms

Marfan syndrome can affect different parts of your body. Not all parts of the body are affected in everyone. Some people with Marfan syndrome may only have a few symptoms or problems, while others are more severely affected. The symptoms tend to become worse as you get older.

The following lists the most common problems and symptoms that may develop. Treatments are available for most of these problems. The treatments are listed later in the article.

The heart and blood vessels

See also the separate leaflet Anatomy of the heart.

• Heart and blood vessel problems are the most serious problems that people with Marfan syndrome tend to have.

• Marfan syndrome can weaken the wall of the main artery in your body (the aorta). Arteries carry blood from your heart to the rest of your body. The aorta runs from your heart, through the centre of your chest and then through the centre of your abdomen. Because the walls of the aorta become weak, it can widen or bulge out. This is known as an aortic aneurysm. See the separate leaflet called Abdominal aortic aneurysm for more details.

• About 8 out of 10 people with Marfan syndrome have widening of this main artery. In severe cases, the widened artery can tear (see the separate leaflet called Aortic dissection for more details) or burst. This can cause severe bleeding and death. Widening of the main artery can be diagnosed at an early age and may then become worse over time.

• Some people with Marfan syndrome have a problem with one of the valves in their heart. The valves separate the chambers of the heart. The problem is called mitral valve prolapse and it happens because the valve called the mitral valve becomes floppy. Your doctor may hear a heart murmur when they listen to your heart. See the separate leaflet called Mitral regurgitation for more details.

The skeleton

• People with Marfan syndrome will usually be taller and thinner than other members of their family who don't have Marfan syndrome.

• Your arms and legs may be longer than other people's.

• Your fingers may be long and thin. This is called arachnodactyly.

• Your breastbone may be pressed inwards and your ribs will curve inwards with it. This is called funnel chest (pectus excavatum). This can become worse with time and cause chest pain and breathing problems.

• Sometimes the breastbone is pushed outwards so your chest is more rounded. This is called pigeon chest (pectus carinatum). It is usually painless and causes no health problems.

• More than 6 out of 10 people with Marfan syndrome have a sideways curve of the backbone (scoliosis). It can cause back pain. In severe cases it can put pressure on the heart and lungs and cause breathing problems. See the separate leaflet called Scoliosis and kyphosis (Curvature of the spine) for more details.

• Flat feet are also common.

• There may be problems with the hip joints, leading to hip pain, stiffness and problems with walking. This may eventually cause arthritis in your hip joints.

• You may have joints which are slack and more flexible than usual.

• Teeth and mouth problems can include a high, arched roof (palate) of your mouth, a small bottom jaw and crowding of your teeth.

The eyes

• In about half of people with Marfan syndrome, the lens in the eye moves into an abnormal position (called a lens dislocation). It can be present at birth or it may develop when you are a child or a teenager.

• Part of the lining of your eye (the retina) may tear or peel away from the back of your eye. This is called a retinal detachment. See the separate leaflet called Retinal detachment for more details.

• Other possible eye problems include short-sightedness (myopia), clouding of the lens within your eye (a cataract) and an increase in pressure within your eye (glaucoma).

• Eye problems in people with Marfan syndrome may cause problems with vision if they are not treated early enough.

Other features

• An air leak from one of your lungs may make the lung collapse. This is called a spontaneous pneumothorax. It will cause sudden chest pain and make you short of breath. See the separate leaflet called Pneumothorax for more details.

• You may also notice stretchmarks if you have Marfan syndrome. Stretchmarks are red/pink or white streaky lines on your skin. They are common during pregnancy or in people who have gained or lost a lot of weight or grown quickly. In people with Marfan syndrome, because the skin is weaker than normal, stretchmarks occur more easily. They are usually found on the shoulders, back and thighs.

• Your brain and spinal cord are surrounded by a special membrane called the dura. In people with Marfan syndrome, the dura may become weak and balloon outwards. This is called dural ectasia, which most often occurs in the lower back area. The ballooning dura can press on the nerves as they leave the spinal cord. This can cause back pain and also weakness and numbness in the legs. It can also cause headaches.

What causes Marfan syndrome?

Marfan syndrome is caused by a change (mutation) in the genetic material on one of your chromosomes (chromosome number 15). The gene that is affected is responsible for making a special protein called fibrillin. The gene is called the fibrillin 1 (FBN1) gene. Fibrillin is an important part of connective tissue in the body. It helps to strengthen connective tissue and make it elastic. If not enough fibrillin is made, this can lead to 'floppy' and weak connective tissue. Fibrillin is found in connective tissue in many parts of your body, including your eyes, your blood vessels, your heart and your bones.

Three in four people who have Marfan syndrome have a parent who also has Marfan syndrome. You can inherit Marfan syndrome from just one of your parents. It is known as an autosomal dominant disorder - this means only one of your parents needs to have the faulty gene to pass it on to you.

One in four people who have Marfan syndrome have it because of a new change in genetic material ('new mutation'). Neither of their parents has the condition. For some reason, the change in the fibrillin gene happened for the first time in the egg or sperm of one of their parents.

How is Marfan syndrome diagnosed?

The diagnosis of Marfan syndrome includes looking at your family history, sometimes doing some genetic tests, and also looking to see if different parts of your body have any of the typical problems.

Your doctor will usually start by asking you questions about your family and asking about any symptoms that you may have which suggest Marfan syndrome. They may then examine you to look to see if you have any of the typical features described above.

Marfan syndrome can sometimes be diagnosed in the womb before birth, or soon after birth. For most people, Marfan syndrome is not diagnosed until later in childhood or in adulthood. This is because it can take time for the typical features and problems of Marfan syndrome to become obvious.

Your family doctor will usually refer you to a specialist if they suspect that you may have Marfan syndrome. This will allow further tests to be carried out. These tests may include:

• Chest X-ray to look for signs of a widened main blood artery in your body (the aorta).

• An ultrasound scan of the heart (echocardiogram, or echo) to look for heart problems and any widening of the aorta.

• Computerised tomography (CT) scan or magnetic resonance imaging (MRI) scan of the chest to look at the aorta, and also of the spine to look for any signs that the membrane surrounding your brain and spinal cord (called the dura) may have become weak and ballooned outwards (known as dural ectasia).

• 24-hour heart tracing (electrocardiogram, or ECG) to look for problems with the rhythm of your heartbeat.

• An examination of your eyes to look for lens dislocation or problems with the lining at the back of your eye (retina).

• X-rays of your hip and pelvis, which may show a problem with your hip.

• Genetic tests - there is no single genetic test that can diagnose Marfan syndrome. This is because not all people with the abnormal gene have Marfan syndrome and in some people with Marfan syndrome the abnormal gene can't be found. Genetic testing is usually done to look for gene mutations. As time goes on, more different genetic mutations are being found.

This picture shows an informal test for Marfan syndrome, called the 'wrist sign' - if the person with Marfan syndrome grips their wrist with their hand, their little finger overlaps their thumb. This occurs in about 6 out of 10 people with Marfan syndrome. It is possible but rare to have this sign without Marfan syndrome.

Marfan syndrome wrist sign

By Staufenbiel I, Hauschild C, Kahl-Nieke B, Vahle-Hinz E, von Kodolitsch Y, Berner M, Bauss O, Geurtsen W, Rahman A, CC BY-SA 2.0, via Wikimedia Commons

Doctors may use the 'Ghent criteria' to help diagnose Marfan syndrome. These include a list of some of the typical features of Marfan syndrome. There needs to be a certain number of features present plus either a relative who has Marfan syndrome or an abnormal genetic test to make a diagnosis of Marfan syndrome.

What is the treatment for Marfan syndrome?

There is no cure for Marfan syndrome. However, treatments are available to help with the problems that Marfan syndrome causes. Because Marfan syndrome may affect different parts of your body, you may be seen by different specialists. These specialists may include a heart specialist (cardiologist), an eye specialist (ophthalmologist), a bone and joint specialist (orthopaedic surgeon) and a specialist in genetic problems (geneticist).

Treatment for heart and blood vessel problems

If you have Marfan syndrome, you will need regular check-ups to look for, and to monitor, any heart and blood vessel problems. For example, you may have regular echocardiography (scans of the heart) to check for widening of your main blood artery (aorta).

There are medicines which may help to slow down any widening of your aorta. Beta-blockers are often prescribed for this reason. Other medicines used include calcium antagonists, ACE inhibitors and angiotensin receptor blockers.

Sometimes heart surgery is needed to repair or replace part of the main artery if it becomes too wide. This is usually advised once the size of the aorta reaches 5cm. This is because there is a risk that the artery may tear or burst suddenly. During surgery, the dilated part of the artery is replaced using a graft. Sometimes the valve between the heart and main blood artery (the aortic valve) is replaced as well. In some people, emergency surgery is needed if the main artery tears or bursts, but the aim of treatment is to operate on the bulging aorta before this. The outcomes from planned surgery are much better than the outcomes from emergency surgery.

Heart surgery may also be needed for mitral valve problems.

Treatment for skeleton problems

A number of the problems with your bones that may occur with Marfan syndrome may require treatment. Physiotherapy is often used for hip pain, back pain or problems with walking.

An abnormal curve of your spine (scoliosis) may be treated with a back brace. The idea is that the brace will stop the abnormal curve from becoming any worse. A brace does not cure the abnormal curve of your spine. It may be particularly useful for children who are still growing. If severe then the abnormal curve of your spine may need surgery. See the separate leaflet called Scoliosis and kyphosis (Curvature of the spine) for more details.

If your breastbone is pressed inwards (pectus excavatum), your lungs and breathing may be affected and you may need to have surgery to correct this.

If your breastbone is pushed outwards (pectus carinatum) this does not usually cause any problems. Some people with their breastbone pushed outwards choose to have corrective surgery for cosmetic reasons.

Surgery may also sometimes be needed to correct hip problems.

Treatment for eye problems

See also the separate leaflet Anatomy of the eye.

• You will be seen regularly by an eye specialist if you have Marfan syndrome.

• Treatment for eye problems may be needed. For example, lasers can be used to repair a problem with the lining at the back of your eye (detached retina).

• If the lens of your eye moves into an abnormal position (dislocated lens), surgery to remove the lens from the eye may be needed.

• If you develop clouding of the lens within your eye (a cataract), you may need the lens in your eye to be removed and an artificial lens put in its place. See the separate leaflet called Cataracts for more details.

• If you develop increased pressure within your eye (glaucoma), treatments may include various eye drops, medicines, laser treatment, and surgery.

• Glasses or contact lenses may be needed if you have short sight (myopia).

Lifestyle changes

Most people with Marfan syndrome can lead relatively normal lives. However, weightlifting and some competitive and contact sports may not be suitable if you have Marfan syndrome.

You may also be advised to avoid scuba diving and climbing. This is because of the weakness in the main blood artery (aorta) and the eye, and any skeletal problems that you may have. Your specialist will advise whether you should avoid any specific activities.

Many activities and sports such as walking, golf and fishing are encouraged if you have Marfan syndrome.

Other treatments

Being diagnosed with Marfan syndrome may be a difficult thing for some people to deal with. For some people, height and appearance may cause some worries and affect confidence and self-esteem. The chance that some major surgery may be needed - for example, heart surgery - can be a difficult thing to deal with as well.

You may find it helpful to join a support group so that you can make contact with other people who have Marfan syndrome. You may also find some individual counselling helpful for both yourself and also your family members.

There may also be some other specialist treatments available for Marfan syndrome. One example is hormone treatment to bring on puberty early in children so that their adult height can be reduced. Your specialist will be able to advise you about the latest treatments.

Can I pass on Marfan syndrome to my children?

Yes - if you have Marfan syndrome, for each child that you have, there is a 50:50 chance that they will also have Marfan syndrome. This also means that there is also a 50:50 chance that each child won't have Marfan syndrome.

Autosomal dominant inheritance

Testing for Marfan syndrome in your baby when you are pregnant can be done using chorionic villus sampling or amniocentesis. It may be able to show whether your baby has the defective gene. However, you should remember that Marfan syndrome is a variable disease. It affects different people in different ways. So a child that you have may be affected less severely, or more severely, than you are.

If you are a woman with Marfan syndrome and you become pregnant, the pregnancy can put an increased strain on your heart. This may increase your chance of the main artery bursting (aortic rupture). You will need regular follow-up with a specialist if you have Marfan syndrome and you become pregnant.

If you (or your partner) have Marfan syndrome and you want to have a child, you may want to seek advice from a specialist in genetic problems (a geneticist) before you get pregnant.

What is the outlook?

The outlook (prognosis) for people with Marfan syndrome is very variable. Some people with the syndrome only have a few problems which don't cause many difficulties. Other people with the syndrome may be severely affected.

If any heart problems are not treated, they can lead to death in some cases. This is the main reason that it is important that Marfan syndrome should be recognised early so that you can have ongoing monitoring, especially of any heart problems. Early recognition of Marfan syndrome will also mean that treatment can be carried out to avoid serious complications. Before new medications and earlier surgery for heart problems, the average life expectancy with Marfan syndrome was 32 years (in 1972); the average life expectancy is now similar to someone without Marfan syndrome.

The main causes of early death in Marfan syndrome now are in people who have not been diagnosed or who are diagnosed very late and when too much damage to the heart has already happened.