Marfan Syndrome

What Is Marfan Syndrome & What Causes It?

Marfan syndrome is one of a family of serious genetic connective tissue disorders. Conditions that can mimic Marfan syndrome and have similar complications include Loeys-Dietz syndrome and vascular Ehlers-Danlos syndrome. Therefore, accurate diagnosis is important to ensure appropriate treatment and risk management. 

Marfan syndrome is caused by an abnormality of the gene that tells your body to produce a protein required for your connective tissue’s elasticity and strength (FBN1; fibrillin-1). Your connective tissue is what keeps your organs and other body structures in place. As a result, Marfan syndrome can affect many parts of your body. However, it most commonly causes problems with the heart, eyes, blood vessels and skeleton. The damage and effects can vary from mild to severe, depending on the individual. Most people with Marfan syndrome, including those with ‘mild’ Marfan syndrome, will develop some form of heart problem. 

Loeys-Dietz syndrome (LDS) and vascular Ehlers-Danlos syndrome (vEDS) are much rarer genetic connective tissue disorders, and are caused by abnormalities of similarly important genes (for example, TGFBR1 and TGFBR2 for LDS and COL3A1 for vEDS). However, as they present similarly to Marfan syndrome, genetic testing is the only way to properly diagnose which condition a person has.

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How Common Is Marfan Syndrome & How Is It Inherited?

Marfan syndrome (and LDS and vEDS) are autosomal dominant disorders, meaning it can be inherited from a parent, and affect men and women equally.

If a person with Marfan syndrome has a child, they have a 50% chance of passing the condition on.

But the condition can also spontaneously occur through a new genetic mutation (also called genetic variant). This is the case for approximately 25% of those with Marfan syndrome.

Overall, for every 10,000 people, Marfan syndrome is predicted to affect 2–3 individuals. While Marfan syndrome cannot be cured, massive improvements in treatments and management of the condition means modern-day patients far exceed the average lifespan of the disorder from even only a few decades ago. Where people with the disorder were once expected to only reach their mid-40s, many now live well into their 70s.

How Does Marfan Syndrome Affect Your Heart?

The faulty connective tissue caused by Marfan syndrome, Loeys-Dietz syndrome and vascular Ehlers-Danlos syndrome can impact your heart in a number of ways, including weakening your aorta, and/or placing increased stress and pressure on your heart muscle. 

As a result, heart problems are common with Marfan syndrome and these similarly presenting conditions:

• Aortic aneurysms, where the aortic wall bulges and develops a weak spot. This is most commonly seen around the aortic root. Aortic aneurysm symptoms include sharp sudden pain in your upper back, and/or in your chest, jaw, neck or arms. You may also have difficulty breathing and lose consciousness. Aortic aneurysm treatment needs to be swift to prevent the aneurysm from rupturing, leading to massive internal bleeding and potentially sudden death.
• Aortic dissections, where the innermost layer of your aorta wall has a tear in it, allowing blood to move in between the layers of the wall. This weakens your aorta’s structure, possibly leading to a ruptured aorta.
• Aortic dissection symptoms to look out for include experiencing severe pain in your chest or back. If an aortic dissection occurs, treatment must be fast, including surgery to remove the dissected aorta (or as much as possible) and to stop blood leaking into the aortic wall.
• Heart valve abnormalities, which are the result of weak tissue in your heart valves becoming stretched. Mitral valve prolapse and aortic valve regurgitation are two examples, where these valves do not properly close and as a result leak. This leaking can make your heart work harder, resulting in heart failure.

Importantly, the heart abnormalities caused by Marfan syndrome can worsen rapidly if you are pregnant due to the increased blood flow and added stress to your aorta. As Marfan syndrome can affect the heart in such a variety of ways, early detection and treatment is strongly recommended. This includes ruling out the possibility that the condition is Loeys-Dietz syndrome or vascular Ehlers-Danlos syndrome.

How Is Marfan Syndrome Diagnosed?

Marfan syndrome, Loeys-Dietz syndrome and vEDS are genetic disorders with variable expression (this means they can present differently in individuals, even within the same family). However, they need to be treated differently. Therefore, a firm diagnosis of Marfan syndrome, Loeys-Dietz syndrome or vEDS most often requires specialised genetic testing. Ideally, this is achieved by working with a service that truly understands the nuances of cardiac genetics, including just how variable the conditions can be between people, how serious they are, and how to arrange and interpret the most appropriate genetic tests. 

If there is no family history of the condition, Marfan syndrome may be indicated by signs and symptoms like:

• Being tall and thin with unusually long arms, legs, fingers and toes, and/or a long, narrow face
• A breastbone that sticks out or dips inward (pectus abnormalities)
• High arched palate and crowded teeth
• Heart murmurs and shortness of breath on exertion
• Severe nearsightedness (myopia) and abnormalities of the lens of the eye (lens dislocation)
• An abnormally curved spine (scoliosis)
• Flat feet

Some children and even babies manifest with clear signs of Marfan syndrome, whereas adults in the same family (including parents of an affected child) can display very mild signs. Marfan syndrome can be diagnosed on the basis of expert assessment by a physician who is familiar with the condition. However, in most cases genetic testing is required to confirm the diagnosis of Marfan syndrome.  Overall, for every 10,000 people, Marfan syndrome is predicted to affect 2–3 individuals.

The first test will likely be to check your heart, in particular the valves and aorta. This is done via an echocardiogram (ultrasound of the heart). You may also be recommended other cardiac imaging, such as CT (computerised tomography) scans and MRIs (magnetic resonance imaging) for a clearer picture of the whole aorta and its major branches.

If your general practitioner or cardiologist suspects that you have Marfan syndrome, they may then recommend genetic testing to confirm the diagnosis. This will be a blood or saliva test to look for changes or abnormalities in your genes (these abnormalities are called mutations or variants). Your test will usually include a panel of genes that covers Marfan syndrome, Loeyz-Dietz syndrome, vEDS and other similar connective tissue disorders. A precise diagnosis is best achieved through comprehensive testing arranged by a service that understands the complexity of this kind of testing. 

How Genetic Testing Can Help

Ultimately, there is no substitute for genetic testing when confirming Marfan syndrome. With specialised tests now available, it’s possible to more accurately diagnose the disease, including identifying exactly which mutation is present. This information is critical for guiding treatment and management. Without genetic testing, your medical evaluation is incomplete. 

Additionally, genetic testing helps to remove the need for complex clinical evaluations for family members. Your diagnosis is a strong indicator that they may have the disease and therefore need to complete genetic testing themselves. When dealing with a disease that can impact your heart in such a serious manner, the earlier the diagnosis the better. Through genetic testing, the likelihood of an early diagnosis is high for your family members.

Does Your Family History Show or Hint at Marfan Syndrome?

As most individuals with Marfan syndrome have inherited it from a parent, having a family history of the condition or a family history of heart issues or sudden death (sometimes recorded as sudden death syndrome) can indicate if you or your loved ones are at risk. Putting together a family tree documenting issues potentially caused by Marfan syndrome can help identify the condition more easily.

It’s best to record family members and their relevant medical history to assist with diagnosis. Additionally, even if your family history does not end up pointing towards Marfan syndrome, there may be connections to other conditions that can become apparent to yourself or a medical health professional. For instance, as Marfan syndrome presents similarly to Loeys-Dietz syndrome and vascular Ehlers-Danlos syndrome, and a service with expertise in these conditions can pick up the possibility of these and many other rare and serious connective tissue disorders through evaluation of your family history.

As you fill out your family tree, think about if any of the following applies to your family:

• Heart conditions, like enlarged hearts or aortas, valve problems, or heart murmurs.
• Sudden unexplained deaths, including sudden cardiac death in young people or individuals after strenuous activity. This may also be recorded as sudden arrhythmic death syndrome or sudden adult death syndrome.
• Anyone who has been told they could have Marfan syndrome or who has a confirmed diagnosis of the condition.