Marfan Syndrome and Genetic Testing

By February 26, 2020 Genetic Counseling
African male pediatrician hold stethoscope exam child boy patient

What is Marfan Syndrome?

Marfan syndrome is a condition of the connective tissue and affects about 1 in every 5,000 individuals. Connective tissue helps provide strength and flexibility to different parts of the body, including our bones and blood vessels.

People with Marfan syndrome can have multiple signs and symptoms, usually in the bones, eyes and heart. People are born with Marfan syndrome, but may not notice any signs until later in life.  Not all individuals with Marfan syndrome will have the same signs, and it is very unlikely that one person will have all of the signs. However, many of these features of Marfan syndrome can get worse as individuals age, so it is important to be monitored for these throughout life.

People with Marfan syndrome may have nearsightedness (myopia) or vision issues caused by a dislocated lens in the eye (ectopia lentis). There may also be other eye-related findings, like cataracts and glaucoma, but these are less common.

The blood vessel affected in people with Marfan syndrome is the aorta, the large artery that carries blood from the heart to the rest of the body. Marfan syndrome causes the aorta to be weakened and prone to aortic dilation (stretching out). As a result of aortic dilation, people may develop aortic aneurysms (bulging/ballooning out of the aorta). Aneurysms typically have no symptoms and can go undetected. Aortic aneurysms increase the risk of an individual having an aortic dissection (tearing within the walls of the aorta). Aortic dissections usually cause severe, sudden chest pain, and may also result in unusually pale skin, a very faint pulse, numbness, tingling or paralysis, and can be life-threatening. Mitral valve prolapse (floppiness of the mitral valve in the heart) can also be commonly seen. Fortunately, there are medical management options to reduce the risk associated with this condition, which is why knowing whether someone has a Marfan syndrome diagnosis  is important.

Other features that can be seen in individuals with Marfan syndrome include long arms and legs, tall and thin body type, long and thin fingers (arachnodactyly), flat feet (pes planus), ankle bones that collapse in (hindfoot deformity) and flexible joint or elbows that can’t straighten all the way. Curvature of the spine (scoliosis or kyphosis) and a chest bone that sinks in (pectus excavatum) or that sticks out (pectus carinatum) are also common. Another sign is a very high and narrow oral palate (roof of the mouth) that can lead to teeth that are overly crowded and individuals needing palate expanders and teeth extractions.There can also be unusual stretch marks on the skin (striae), recurrent hernias and the sudden collapse of the lung (spontaneous pneumothorax).

Understanding the Genetics of Marfan Syndrome

Marfan syndrome is a genetic condition caused by alterations (changes) in one of our body’s genes . The specific gene that is altered in Marfan syndrome is called FBN1. This gene provides the instructions for a protein that helps make up the body’s connective tissue, supports the structures of the eyes and helps with the regulation of bone growth and growth of other parts of the body.  When there are alterations or variants in FBN1, the connective tissue does not function normally, which leads to the features of Marfan syndrome.

Is Marfan Syndrome Hereditary?

Because Marfan syndrome is a genetic disorder, it can be hereditary — meaning it runs in families. Variants in the FBN1 gene are inherited (passed down in a family) in an autosomal dominant pattern. This means that individuals with Marfan syndrome can pass this condition onto their children. Autosomal means that both men and women can inherit FBN1 variants and have Marfan syndrome. Dominant means that only one copy of the FBN1 genes must have a disease-causing variant to cause Marfan syndrome. All people have two copies of the FBN1 gene, one from each parent. A person who has a parent with Marfan syndrome and an FBN1 variant may inherit either the parent’s FBN1 gene with the variant or the parent’s working gene (the copy without a mutation). Therefore, that individual has a 50% chance of inheriting the FBN1 gene variant and also having Marfan syndrome.

Sometimes a person may be diagnosed with Marfan syndrome and have no family history. This may occur either when one of the parents has Marfan syndrome but is mildly affected or when the FBN1 variant happened for the first time in that person. When a gene variant happened for the first time in a person, it is referred to as a de novo change. De novo variants happen in the FBN1 gene in 25% of people with Marfan syndrome. Someone who has a de novo FBN1 variant will not have parents or siblings that are affected, but will still have a chance to have affected children.

Once an individual with Marfan syndrome has had genetic testing and an underlying genetic variant has been identified, this allows the rest of the family to have testing for the same variant. Testing the at-risk family members helps determine if they have Marfan syndrome and are at risk for Marfan-related features, like aortic aneurysms and dissection.

Marfan Syndrome Genetic Testing

While Marfan syndrome can be diagnosed based on clinical features alone, genetic testing of the FBN1 gene and related connective tissue conditions, like Loeys-Dietz syndromes, is important. As mentioned above, some features of Marfan syndrome may develop with age or a person may never develop some features. Genetic testing can help confirm when there is suspicion that a person may have Marfan syndrome but doesn’t yet have enough features to meet the criteria for clinical diagnosis.

Using genetic testing to help confirm a diagnosis can guide an individual’s medical management. It is recommended that anyone found to have an FBN1 gene disease-causing variant be evaluated annually (every year) by a cardiologist  and ophthalmologist . Annual cardiology checkups and echocardiograms (ultrasound of the heart) help doctors monitor and evaluate the size of the aorta and how the heart is working. Some heart problems can be managed with medications, such as beta-blockers, which help decrease the stress on the aorta and slow progression of aortic dilation. If the aorta reaches a certain size, surgery may be recommended to repair the aorta in order to avoid an aortic dissection.

Additionally, some people that have a clinical diagnosis of Marfan syndrome may actually have a variant in a different gene identified through genetic testing. This is because there are other conditions that affect the body’s connective tissue that can present very similarly to Marfan syndrome, causing similar heart problems and other body features. Confirming that someone has a genetic variant in the FBN1 gene versus a different gene is important because it can impact a person’s medical care. Some of the related conditions can have dilation of arteries other than the aorta, needing periodic imaging of the body’s vessels in addition to the ultrasound of the heart. Additionally, the other conditions may have different surgical recommendations regarding when to repair an aortic aneurysm.

Once an individual with Marfan syndrome has had genetic testing and an underlying genetic variant has been identified, this allows the rest of the family to have testing for the same variant. Testing those at-risk family members helps determine if they have Marfan syndrome and are at risk for Marfan-related features, like aortic aneurysms and dissection, and helps guide their screening recommendations.

A genetic counselor can help determine what genetic testing options are best for you based on your personal and family history. Visit to learn more.