Genetics Northern California

Marfan syndrome

General Information
Marfan syndrome belongs to a category of disorders known as connective tissue disorders. Connective tissue provides strength and flexibility to different parts of your body. In Marfan syndrome, the connective tissue does not function in the normal way. This difference in the connective tissue can affect bones, joints, eyes, blood vessels, heart, and other organs. Marfan syndrome is quite variable, which means that no two individuals with Marfan syndrome will have exactly the same features, even if they are in the same family.

Marfan syndrome is thought to affect about 1 in 5,000 people. It affects both males and females of all racial and ethnic backgrounds. It is caused by a genetic change (mutation) in a gene called fibrillin-1 (FBN1). Marfan syndrome is an autosomal dominant condition, which means that a mutation in just one copy of the FBN1 gene can cause Marfan syndrome. Most people who have Marfan syndrome have a parent who also has Marfan syndrome. In some cases the parent may be unaware that they have the condition. Other times, there is no one else in the family with Marfan syndrome. About 1 in 4 people with Marfan syndrome are the first person in the family to have the condition due to a de novo mutation in the FBN1 gene. Any person who has Marfan syndrome can pass the condition to his/her children. Each child of a parent with Marfan syndrome has a 50% chance of inheriting the condition.

Features of Marfan Syndrome
The most common body parts affected by Marfan syndrome are the bones and joints, eyes, blood vessels and heart.

Bones and joints: People with Marfan syndrome are often taller than average. They can have long, thin fingers and long faces. They sometimes have curving of the spine (scoliosis) and may have a chest that seems to stick out or cave in. Loose joints are also common.

Eyes
: Near-sightedness (myopia) is very common in Marfan syndrome, but is also present in many people without Marfan syndrome. Sometimes the lens of the eye can shift out of place because the connective tissue is formed differently. This is considered to be a hallmark feature of Marfan syndrome because it does not happen very often to someone without a connective tissue disorder.

Blood vessels and heart
: The blood vessels and heart can be affected in different ways. The most common finding involves a heart valve not closing properly (mitral valve prolapse or tricuspid valve prolapse). In most cases this does not cause serious medical problems. The weaker connective tissue in Marfan syndrome can also lead to gradual enlargement of the aorta. The aorta is the large artery that carries blood out of the heart into the body. Weakness in the aorta can result in rupture or tearing of the blood vessel.

Other features sometimes seen in people with Marfan syndrome include recurrent hernias and pneumothorax (collapsed lung). People with Marfan syndrome typically have normal intelligence.

Diagnosing Marfan syndrome
Marfan syndrome is usually diagnosed in a genetics clinic by reviewing the family history and performing a specialized physical exam. There are specific criteria that doctors use to decide if a person has Marfan syndrome. Genetic testing is generally not needed to make a diagnosis.

Genetic Testing
Genetic testing may be useful in some situations. Between 70-90% of people with a clinical diagnosis of Marfan syndrome have a detectable mutation in the fibrillin-1gene (FBN1).  The remaining 10-30% of people with Marfan syndrome have a mutation that our current testing is not able to find. A negative genetic test (no mutation found) does not change the diagnosis. If the specific mutation of someone with Marfan syndrome is known, prenatal diagnostic testing is available during pregnancy.

Treatment of Marfan Syndrome
The best treatment for someone with Marfan syndrome is specialized care for symptoms related to the condition. Regular monitoring by a cardiologist is important. Medications can be used to slow or prevent enlargement of the aorta. If the aorta gets too large, surgery is needed to prevent it from breaking open (rupture or dissection). There may also be the need for regular appointments with an ophthalmologist or an orthopedist.

People with Marfan syndrome are encouraged to participate in non-contact sports, such as swimming, and to avoid contact sports, such as football or wrestling, due to the potential risk for blood vessel or eye problems. Isometric exercises, like weight lifting, are not recommended because of the strain they place on the blood vessels.  Scuba diving is not recommended because of the potential for lung collapse. You can speak with your doctor for advice on appropriate physical activities for people with Marfan syndrome.

Support Resources
National Marfan Foundation
www.marfan.org

References
American Academy of Pediatrics Health Supervision for Children with Marfan syndrome:
http://aappolicy.aappublications.org/cgi/reprint/pediatrics;98/5/978.pdf

Gene Reviews on Marfan Syndrome:
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=marfan

NIH: Genetics Home Reference on Marfan syndrome:
http://ghr.nlm.nih.gov/condition/marfan-syndrome


Written by:     Elizabeth Stark, MS

Reviewed by:  Kim Barr, MS CGC
                     Emily Chen, MD PhD
                     Bruce Blumberg, MD

Last Edited: August 4 2010