Marfan syndrome

Marfan syndrome is caused by a change in a gene that affects connective tissue. Connective tissue supports many structures in the body, including bones, tendons, ligaments, cartilage, heart valves and blood vessels. While most cases of Marfan syndrome are inherited, some are due to a spontaneous gene change, with no family history.

The condition can range from mild to severe, and may become worse with age depending on which areas are affected and to what degree. There is no cure, but the potential complications can be managed, so early and accurate diagnosis is essential.

Recent estimates suggest one in 3,000 to 5,000 people have Marfan syndrome. Men, women and people of all backgrounds have a similar risk.

How Marfan syndrome affects the heart#

In Marfan syndrome, the heart is often affected. The aorta, the major artery of the body, may be more dilated (widened) than average. This can cause the aorta to tear or bulge under pressure, for example during strenuous exercise or childbirth, leading to bleeding into the layers of the aorta or an increased risk of an aneurysm.

If the heart valves are affected, blood may seep backwards and place extra strain on the heart, which may then enlarge to cope with the extra workload. A heart valve affected by Marfan syndrome, such as the mitral valve, is not as stiff and resilient as it should be, so it can collapse backwards under pressure. This is called mitral valve prolapse. To cope with the backflow, the heart has to work much harder to pump blood around the body.

People whose Marfan syndrome affects their heart valves are at increased risk of endocarditis, an infection of the heart wall or valves, which can have life-threatening consequences. Before various types of surgery, a preventative course of antibiotics may be recommended to reduce this risk.

Symptoms#

The symptoms of Marfan syndrome differ from one person to the next, depending on which body part is affected and to what degree. Some people may not even realise they have the condition, because their features are mild or not obvious.

Symptoms may include:

• a long, narrow face, a proportionately small lower jaw, and a narrow, highly arched palate
• usually a tall, lean stature with disproportionately long arms and legs
• thin, long fingers and toes (arachnodactyly)
• a sunken or protruding chest
• loose and flexible joints, often prone to dislocation
• scoliosis (a sideways curve in the spine)
• visual problems, such as nearsightedness (myopia) or dislocation of the lens of the eye
• stretch marks (striae), which often appear at an early age and are not related to weight change
• dural ectasia – enlargement of the membrane around the brain and spinal cord, usually affecting the lower spine and causing no symptoms
• an enlarged aorta and mitral valve prolapse
• pneumothorax – spontaneous collapse of a lung

Causes#

Marfan syndrome is caused by a change in the FBN1 gene. This gene affects the composition of fibrillin, an important substance that contributes to the integrity of connective tissue.

A child of a person with Marfan syndrome has a one-in-2 chance of inheriting the condition. Around three out of four cases are inherited from one affected parent, while around one in four are due to a spontaneous change in the FBN1 gene before conception, for reasons unknown.

Research into the condition is ongoing, with the hope of developing more specific genetic tests for earlier and more accurate diagnosis. With advances in genetic testing, other genes have recently been found that might account for a small proportion of cases and some condition-related symptoms.

Diagnosis#

A specific collection of major characteristic features must be present to establish the syndrome. A confirmed diagnosis requires coordinated evaluation by a cardiologist, ophthalmologist, orthopaedic surgeon and geneticist, all experienced with Marfan syndrome.

The condition is diagnosed using a number of tests, which may include:

• gene testing and comparison with a genetic database
• physical examination
• family history
• echocardiogram (a picture of the heart using sound waves)
• eye examination, using a slit lamp to detect dislocated lenses
• skeletal tests such as X-rays

Over time it has become apparent that a small proportion of people previously thought to have Marfan syndrome actually have a related but distinct condition called Loeys-Dietz syndrome. This shares many features with Marfan syndrome, but people with Loeys-Dietz syndrome have more aggressive blood vessel disease and do not develop the eye complications seen in Marfan syndrome.

Treatment#

There is currently no cure for Marfan syndrome. Depending on which body parts are affected and to what degree, regular monitoring and treatment may include:

• regular check-ups to monitor the skeleton and offer corrective treatment if necessary, which is particularly important during the growth spurt of puberty
• medication, such as beta-blockers, to reduce blood pressure and relieve strain on the cardiovascular system
• a course of antibiotics to prevent infection before any surgery involving the teeth, genitals or urinary system, to reduce the risk of heart valve problems including endocarditis
• regular echocardiograms and other tests to monitor the size and function of the heart and aorta
• regular eye examinations and treatment
• heart surgery, such as surgical repair of valves or the aorta

The expected lifespan of a person with Marfan syndrome used to be around the mid-40s, but now extends into the 70s, which is comparable to the general population. This improvement is mainly due to improved awareness of the condition among health professionals, early diagnosis, advances in medical management and medication, more effective surgical techniques, and appropriate lifestyle changes.

Living with Marfan syndrome#

If you have Marfan syndrome, it is important to be well informed about the condition and how it can be managed. General wellbeing and quality of life can be improved by making lifestyle choices that reduce the stress on your body. A healthcare professional can advise you on suitable changes, which may include:

• avoiding contact sports
• doing only gentle to moderate exercise
• avoiding physical activities that depend on isometric exercise, such as weight training or moving heavy objects

A woman who has a dilated aorta requires specialised counselling about the higher risks involved when considering a pregnancy, due to the strain on this major artery and the risk of rupture, particularly during childbirth. Cardiac assessment before pregnancy and repeatedly throughout pregnancy is recommended.

Genetic counselling#

If you or a family member have been diagnosed with Marfan syndrome, or if it runs in your family, it can be helpful to speak to a genetic counsellor. Genetic counsellors are health professionals qualified in both counselling and genetics.

As well as providing emotional support, they can help you understand Marfan syndrome and what causes it, how it is inherited, and what a diagnosis means for your or your child’s health and development. Genetic counsellors are trained to provide information and support that is sensitive to your family circumstances, culture and beliefs.

If Marfan syndrome runs in your family, a genetic counsellor can explain the genetic testing options available to you and other family members. You may choose to see a genetic counsellor if you are planning a family, to find out your risk of passing the condition on to a child, or to arrange prenatal tests. Support groups can also connect you with other individuals and families affected by Marfan syndrome.

Key points#

• Marfan syndrome is caused by a change in a gene that affects connective tissue.
• The aorta can tear or bulge under pressure, for example during strenuous exercise or childbirth, which can cause bleeding into the layers of the aorta or increase the risk of an aneurysm.
• Other common problems include spinal curvature (scoliosis) and nearsightedness.
• Men, women and people of all backgrounds have a similar risk.

Where to get help#