How is Marfan syndrome diagnosed?
Marfan syndrome is based on a clinical diagnosis. A multidisciplinary approach is necessary to make the diagnosis because multiple organ systems must be assessed. Members of the team will assess the eyes, heart and blood vessels, spine and skeletal system.
A thorough history of symptoms and information about family members that may have had related problems are also necessary. Other tests, such as chest x-ray, electrocardiogram (ECG) and echocardiogram (an imaging procedure that uses high frequency sound waves to produce a moving picture of the heart's valves and chambers) will be used to evaluate changes in the heart and blood vessels, and detect heart rhythm problems.
If sections of the aorta are not able to be visualized through echocardiogram, or a dissection is already suspected, a transesophageal echo (TEE), magnetic resonance imaging (MRI), or computed tomography (CT) scan may be needed.
Often a CT or MRI is also needed to evaluate for something called dural ectasia. Dural ectasia is a bulging of the lining of the spinal column. It often does not cause any symptoms but it can be associated with back pain in some patients. Dural ectasia is a feature that helps to support the diagnosis of Marfan syndrome but it can also occur with other connective tissue disorders.
A blood test can be used to help diagnose Marfan syndrome. This blood test is highly specialized and looks for changes in FBN1, the gene that is responsible for most cases of Marfan syndrome.
Genetic counseling should accompany genetic testing because FBN1 testing is not always straightforward. Blood tests also can be used to help in the diagnosis of other genetic mutations, such as Loeys-Dietz syndrome, that cause physical findings similar to Marfan syndrome. Learn more about genetic counseling.
What is genetic testing?
Genetic testing is a specialized laboratory test that looks for changes (also called mutations) in a person’s genetic material (DNA, genes or chromosomes) or in the products that the genes make. A gene contains instructions for our bodies. Genes are made up of chemical bases represented by the letters A, T, C and G. Every gene contains thousands of letters. Most times genetic testing is done by taking a blood sample, but sometimes other body samples (like cheek cells or skin) are needed. FBN1 testing is expensive (approximately $2000).
It is often covered by insurance but this varies depending on individual insurance policies. We recommend that you check with your insurance company about coverage prior to having testing.
FBN1 is a large gene and mutations can be found throughout the gene. Over 2,000 different mutations have been identified in FBN1; most mutations are unique to an individual family. Once a mutation is found in one family member, we expect that same mutation to be present in affected family members. In some cases, a change in the genetic code is found that the lab is not able to determine if it actually causes Marfan syndrome. These types of mutations are called variants. When variants are identified, sometimes it is necessary to test other family members (often parents) to try to determine its significance. The lab may also identify changes in the gene called polymorphisms. Polymorphisms are gene changes that are relatively common and are not likely to cause Marfan syndrome.
Who should have genetic testing?
There are numerous reasons that someone should consider genetic testing for Marfan syndrome, these include:
- Someone with a clinical diagnosis who is interested in genetic testing so that other family members can get tested. (Genetic testing should be initiated in someone with Marfan syndrome first and once a mutation is identified other family members can have testing for that mutation at a reduced cost.)
- Someone with a clinical diagnosis who would like to confirm the diagnosis. (It should be noted that not all cases of Marfan syndrome can be confirmed through genetic testing. Therefore, when a person with a diagnosis of Marfan syndrome does not have a mutation in FBN1 it does not mean that he/she does not have Marfan syndrome. It just means that it was not possible to find the genetic reason with current technology.)
- Someone in whom a diagnosis is suspected but clinical evaluation did not establish the diagnosis
- Someone in whom Marfan syndrome is one of several diagnoses that are being considered.
- Family members of someone with an identified mutation.