What is Marfan syndrome?

Marfan syndrome is a genetic disorder of the connective tissue, in particularly affecting the heart, blood vessels, skeleton and eyes. Connective tissue provides the structural support and helps to maintain the elasticity of the ligaments, skeletal structures, blood vessel walls and the heart valves.

How common is Marfan syndrome?

It is estimated that one in 5,000 to 10,000 people are born with Marfan syndrome. It can occur in all races and affect both genders equally.

What are the features of Marfan syndrome?

While Marfan syndrome may be present at birth, some symptoms develop gradually over a number of years. The severity of symptoms varies from person to person, even among affected family members.

The main features include:

• Cardiovascular (heart and blood vessels). Weakening and stretching of the blood vessels can occur. This applies in particular to the aorta (the main blood vessel carrying blood away from the heart) and increases the risk of aortic aneurysm, dissection or rupture (bursting).
  
  The heart’s valves may also be affected. The most common condition is mitral valve prolapse (MVP). In MVP, the valve leaflets become floppy and do not close tightly. This can cause leakage of blood backwards across the valve. This is known as mitral regurgitation (MR). If mitral regurgitation progresses and is left untreated, it can eventually cause heart failure.

• Lungs. Asthma, emphysema, pneumothorax (collapsed lung)
• Skeleton. Tall and thin with long arms, legs, fingers and toes. Flat feet, protruding or indented chest bone, loose joints, scoliosis and skin stretch marks.
• Eyes. Dislocation of lenses, myopia (shortsightedness), retinal detachment, glaucoma
• A family history of Marfan syndrome in a parent, sibling or child

When should you see a doctor?

Seek medical attention if there is:

• Chest pain or breathlessness 
  
• Sudden blurring of vision
  
• Joint pain
  

What causes Marfan syndrome?

Marfan syndrome is caused by changes in the FBN1 gene located on chromosome 15. Genes are instructions for cells to make proteins in the body. Marfan syndrome is the result of a change (mutation) in the FBN1 gene.

This gene controls the production of fibrillin-1, which is a very fine fibre that is found in connective tissue. Fibrillin fibres come together to form an elastic mesh which helps to support certain structures in our body, such as blood vessel walls and the lens of the eye.

Fibrillin-1 also regulates the activation of transforming growth factor beta (TGF-β) binding protein, which takes part in the regulation of many different cell functions and affects connective tissues throughout the body.

Everyone carries two copies of each gene, one inherited from each parent. Marfan syndrome follows a dominant inheritance pattern, which means the presence of one faulty FBN1 gene can cause the condition.

Is Marfan syndrome inherited?

If either parent has Marfan syndrome, a child has a 50% chance of inheriting the disease.

Among people with the condition, about 75% of them would have inherited the genetic change from one of their parents. As some people may have a mild form of the disorder, the parent may not have been previously recognised as having Marfan syndrome.

The other 25% of people with Marfan syndrome have it because of a new mutation in the gene.

How is Marfan syndrome diagnosed?

Marfan syndrome is diagnosed based on a full evaluation by a doctor familiar with the disorder. This involves the following:

• Thorough physical examination
• Complete family history
• Full eye examination
• Echocardiogram (ultrasound of the heart)
• Genetic testing for a causative mutation in the FBN1 gene can also provide helpful information
• Full eye examination in some cases
  

Can Marfan syndrome be cured?

While it is not possible to cure Marfan syndrome, much can be done to make sure you/your child has the best possible outcome.

How is Marfan syndrome managed?

The multidisciplinary medical team looking after you/your child will be able to address specific medical concerns and routine Marfan syndrome-related health issues.

Management measures may include:

• Regular echocardiograms to assess the heart and width of the aorta. Medications and/or surgery may be required if the width of the aorta gets too wide.
• Maintaining good dental and skin hygiene, which is important to reduce the risk of infection of the heart valves.
• Antibiotic prophylaxis may be required before surgery and dental procedures in some cases. Please discuss with your doctor for the latest update on antibiotic prophylaxis.
• Careful monitoring of the skeleton to detect problems with the spine or chest bone.
• Regular eye examinations to monitor for myopia and lens dislocations.

There are also important lifestyle considerations for an individual with Marfan syndrome:

• Ensure a balanced diet, engage in low-intensity exercise and avoid smoking. These measures are also good for general health.
  
• Avoid heavy weightlifting and contact sports. Discuss with your doctor about recommendations for exercise and activities.
  
• With proper management of the cardiovascular manifestations, the life expectancy of someone with Marfan syndrome approximates that of the general population.
  

• Pregnant women with Marfan syndrome may be at high risk of obstetric and cardiac complications due to increased stress of the aortic wall especially during delivery. Please consult your doctor for preconception care and counselling.
  

How likely will I have a child with Marfan syndrome if I have it?

If a parent has Marfan syndrome, the risk of having a child inherit the gene that causes it is 50% in every pregnancy.

How likely will I have another child with Marfan syndrome if neither my spouse nor I have it?

In about 25% of cases, Marfan syndrome is the result of a spontaneous change (mutation) in the genetic material of the sperm or egg at conception in families with no previous history of the disease.

In such cases, the risk of having another child with the disorder is low (< 1%).

Marfan syndrome is a lifelong condition. Should you require financial assistance or emotional support, please approach your doctor for referral to a medical social worker.

Download the Marfan Syndrome brochure.

References

1. Marfan Syndrome: Public education. (2024). Marfan Syndrome, 1–8. https://doi.org/10.36255/marfan-syndrome-public-education

2. Marfan syndrome symptoms, causes, treatment: Nord. National Organization for Rare Disorders. (2024, March 20). https://rarediseases.org/rare-diseases/marfan-syndrome/

3. Marfan syndrome. Marfan Foundation. (2022, October 6). https://marfan.org/conditions/marfan-syndrome/

4. Centers for Disease Control and Prevention. (n.d.). About Marfan syndrome. Centers for Disease Control and Prevention. https://www.cdc.gov/heart-disease/about/marfan-syndrome.html