Marfan's Syndrome

What is Marfan's syndrome and how common is it?

Marfan's syndrome is a genetic disorder that is usually inherited from one of your parents. There is a problem with the connective tissue in your body. (Your connective tissue supports, binds or separates other tissues and organs within your body and can also be a kind of 'packing' tissue in your body.) In Marfan's syndrome, your connective tissue becomes weak and 'floppy'.

Marfan's syndrome can affect connective tissue in different parts of your body including your heart, blood vessels, eyes and skeleton. It can affect different people in different ways and to different degrees. Some people with Marfan's syndrome are only mildly affected while others are more severely affected.

Marfan's syndrome is thought to affect about 1 in 5,000 people. It affects both males and females equally. It is the most common problem affecting connective tissue.

What causes Marfan's syndrome?

Marfan's syndrome is usually caused by a mutation (a change, or fault, in the genetic material) in the fibrillin 1 (FBN1) gene on one of your chromosomes (chromosome 15). This gene is responsible for the production of a special protein called fibrillin. Fibrillin is an important component of connective tissue in the body. It helps to strengthen connective tissue and make it elastic. So, 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 and your bones.

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

One in four people has Marfan's syndrome because of a 'new mutation'. Neither of their parents has the condition. For some reason, the mutation in the fibrillin gene happens for the first time in the egg or sperm of one of their parents.

What are the features of Marfan's syndrome?

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

The following lists the most common problems and symptoms that may develop.

The heart and blood vessels

• Heart and blood vessel problems are the most serious in people with Marfan's syndrome.
• Marfan's syndrome can make the wall of your aorta, the main artery in your body, weak. Your aorta runs from your heart, through the centre of your chest, and then through the centre of your abdomen. It then divides into branches that supply blood to your legs. Because the walls of the aorta are weak, it can widen or 'bulge out'. This is known as an aneurysm. About 7-8 out of 10 people with Marfan's syndrome have widening of the aorta. In severe cases, the widened aorta can tear or rupture. This can cause severe internal bleeding and possible death. Widening of the aorta can become obvious at an early age and get worse over time. It seems to be more common in males than females.
• Some people with Marfan's syndrome have mitral valve prolapse. This is where one of the valves that separate the chambers of your heart becomes floppy. Your doctor may hear a heart murmur when they listen to your heart.

The skeleton

• If you have Marfan's syndrome you will generally be taller and thinner than other members of your family without Marfan's syndrome.
• Your arms and legs may be disproportionately longer than your body. Your arm span may be greater than your height.
• Arachnodactyly is common. This is where you have unusually long and slender fingers.
• You may have pectus excavatum. This is sometimes called funnel chest. Your breast bone is depressed inwards and your ribs can curve inwards with it. This can worsen over time in some people. In severe cases, it can lead to chest pain and breathing problems.
• You may have pectus carinatum. This is sometimes called pigeon chest. This is the opposite of pectus excavatum. Your breastbone protrudes forwards so that your chest is more rounded than usual. It is usually painless and causes no health problems.
• More than 6 out of 10 people with Marfan's syndrome have scoliosis. This is where you have lateral (sideways) curvature of your backbone. It can lead to back pain and deformity. In severe cases it can put pressure on your heart and lungs and cause breathing problems.
• Flat feet are another common feature.
• Hip joint deformity (called protrusio acetabuli) can occur leading to hip pain, stiffness, problems walking and eventually osteoarthritis.
• You may have hypermobile joints. This means that your joints are very loose and flexible.
• Teeth and mouth problems can include a high, arched palate, a small bottom jaw and crowding of your teeth.

The eyes

• About half of people with Marfan's syndrome have lens dislocation. This means that your lens within your eye moves, or falls, into an abnormal position. It can be present at birth or it may develop during childhood or adolescence.
• Retinal detachment or retinal tears are also common. Your retina is the tissue at the back of your eye. Retinal detachment is where the retina peels away from the back of your eye.
• Other possible eye problems include myopia (short-sightedness), cataracts (clouding of the lens within your eye) and glaucoma (an increase in pressure within your eye).
• Eye problems associated with Marfan's syndrome may lead to loss of vision if they are not recognised and treated.

Other features

• A spontaneous pneumothorax can happen in some people with Marfan's syndrome. This is where air leaks out from one of your lungs causing it to collapse. You may experience sudden chest pain and shortness of breath.
• You may also notice stretch marks if you have Marfan's syndrome. Stretch marks 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. In people with Marfan's syndrome, because the skin is weaker than it should be, stretch marks can occur more easily. They are usually found on your shoulders, mid-back, and thighs.
• Dural ectasia may also occur. Your brain and spinal cord are surrounded by a special membrane called the dura. In dural ectasia, the dura becomes weakened and it can balloon outwards. Dural ectasia most commonly occurs in the lower back area. The ballooning dura can press on the vertebrae of the backbone and also your nerves as they leave the spinal cord. This can lead to low back pain, weakness, and loss of sensation in your legs. It can also cause headache.

How is Marfan's syndrome diagnosed?

The diagnosis of Marfan's syndrome is quite complex. It involves 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 enquiring about any symptoms that you may have which may suggest Marfan's syndrome. They may then examine you to look to see if you have any of the typical features. For example, an arm span greater than your height, a high, arched palate, etc.

Marfan's syndrome can sometimes be diagnosed prenatally (see below). In a few other cases, Marfan's syndrome is diagnosed at birth. However, for most people, Marfan's syndrome is not diagnosed until later in childhood, adolescence or adulthood. This is because it can take a while for the typical symptoms and problems of Marfan's syndrome to become obvious.

Your doctor will usually refer you to a specialist if they suspect that you may have Marfan's syndrome. This will allow further tests to be carried out to look for the typical problems that are associated with the syndrome and to confirm the diagnosis. Tests may include:

• Chest X-ray to look for signs of a widened aorta.
• Echocardiogram (an ultrasound scan of the heart) to look for heart problems and any widening of the aorta.
• CT or MRI scans of the chest to look at the aorta, and also of the spine to look for dural ectasia.
• 24-hour ECG recording to look for heart rhythm problems.
• An examination of your eyes to look for lens dislocation, retinal tears and any other eye problems.
• Hip/pelvis X-ray may show the hip deformity, protrusio acetabuli.
• Genetic tests - unfortunately there is no single genetic test that can diagnose Marfan's syndrome. Sometimes genetic testing is done to look for gene mutations but, most of the time, the diagnosis of Marfan's syndrome is made by the typical symptoms and problems that are found on other testing.

There are also some special criteria called the Ghent criteria that doctors can use to help to diagnose Marfan's syndrome. The criteria include some of the typical features that are discussed above, as well as things like a family history of Marfan's syndrome. A certain number of criteria need to be met to make a diagnosis of Marfan's syndrome.

What is the treatment for Marfan's syndrome?

There is no cure for Marfan's syndrome. However, various treatments are available to help with the problems that Marfan's syndrome causes. Because Marfan's syndrome may affect different parts of your body, you may have follow-up with a number of different specialists. For example, a cardiologist (heart specialist), an ophthalmologist (eye specialist), an orthopaedic surgeon (bone and joint specialist), a geneticist (a specialist in genetic problems), etc.

Treatment for heart and blood vessel problems

If you have Marfan's syndrome you will have regular check-ups to look for, and to monitor, any heart and blood vessel problems. For example, you may have regular echocardiography to check for widening of your aorta.

There are various drugs that may help to slow down any widening of your aorta. Beta blockers are commonly prescribed for this reason. Other drugs including a group of drugs called calcium antagonists, another group called ACE inhibitors, and another drug called losartan which may also be used. The results from more clinical trials are needed to determine exactly which drug is best to help slow down aortic widening and exactly when drugs should be started.

Sometimes heart surgery is needed to repair or replace part of the aorta if it becomes too wide. This is because there is a risk that the aorta tears or ruptures suddenly. During surgery, the dilated aortic segment is replaced using a graft. Sometimes the aortic valve is replaced as well. You will be followed up carefully to determine if and when you need surgery. In some people, emergency surgery is needed if the aorta does rupture or tear.

Heart surgery may also be needed for mitral valve problems.

Treatment for skeletal problems

A number of the skeletal problems that may occur with Marfan's syndrome may require treatment. Physiotherapy is commonly used for various problems; for example, hip pain, back pain or mobility problems. However, sometimes other treatments are needed.

Scoliosis may be treated initially with a back brace. The idea is that the brace will stop the scoliosis from getting any worse. A brace does not cure scoliosis. It may be particularly useful in children who are still growing. If severe, scoliosis may need corrective surgery. See separate leaflet called 'Scoliosis (Curvature of the Spine)' which discusses scoliosis in more detail.

If you have pectus excavatum that affects your lungs and breathing, you may need to have corrective surgery for this. This involves raising your breastbone and ribs and holding them in place with a metal bar. The bar is then removed at a later stage. Pectus carinatum does not usually cause any problems. However, some people with pectus carinatum choose to have corrective surgery for cosmetic reasons. Also, surgery may sometimes be needed to correct hip problems.

Treatment for eye problems

You will be seen regularly by an eye specialist if you have Marfan's syndrome. Treatment for eye problems may also be needed.

For example, lasers can be used to repair a detached retina. If you have a dislocated lens, sometimes surgery to remove the lens from within the eye is needed. If you develop cataracts, you may need the lens within your eye replaced by an artificial lens. If you develop glaucoma, possible treatments include various eye drops, drugs, laser and surgery.

Glasses or contact lenses may be needed if you have myopia (short-sightedness).

Lifestyle changes

Most people with Marfan's syndrome can lead relatively normal lives. However, some people may be advised to take care when they participate in certain sports. Some competitive and contact sports may not be suitable if you have Marfan's syndrome. You may also be advised to avoid scuba diving, climbing and weight lifting. This is because of the weakness in the aorta and the eye and the skeletal problems that you may have. Your specialist will advise if you should avoid any specific activities.

However, non-strenuous activities and sports such as golf, walking and fishing are encouraged if you have Marfan's syndrome.

Other treatments

Being diagnosed with Marfan's syndrome may be a difficult thing for some people to deal with. Your height and appearance may cause some worries and affect your confidence and self-esteem. The chance that you may need some major surgery, 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's syndrome. (Contact information can be found below.) 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's syndrome. One example is hormone treatment to bring on puberty early in children so that ultimate adult height may be reduced. Research means that treatments may change and new treatments may become available for Marfan's syndrome. Your specialist will be able to advise you about the latest treatments.

Can I pass on Marfan's syndrome to my children?

Yes - if you have Marfan's syndrome, for each child that you have, there is a 50:50 chance that they will also have Marfan's syndrome.

What is the prognosis (outlook)?

The fact that Marfan's syndrome can affect your heart is the major risk associated with Marfan's syndrome. If heart problems are left untreated, they can lead to death in some cases. For this reason, it is important that Marfan's syndrome is recognised early so that you can have continuous monitoring, especially of any heart problems, and treatment can be carried out to avoid complications such as aortic rupture or tearing. Rarely, eye problems related to Marfan's syndrome can lead to loss of vision.

Improved detection and diagnosis of Marfan's syndrome, as well as timely and improved surgical techniques, and the use of drugs, such as beta blockers to slow widening of the aorta, are all helping to improve prognosis in Marfan's syndrome.

Further help and information

Marfan Association UK

Rochester House, 5 Aldershot Road, Fleet, Hampshire GU51 3NG
Tel: 01252 810 472
Web: www.marfan-association.org.uk
Exists to support those with the syndrome and their families.