Overview of Marfan Syndrome

Marfan syndrome is a genetic disorder that changes the proteins that help make healthy connective tissue. This leads to problems with the development of connective tissue, which supports the bones, muscles, organs, and tissues in your body. Mutations (changes) to a specific gene cause Marfan syndrome, and most people inherit the disorder from their parents.

Symptoms of Marfan syndrome can be mild to severe and vary because the condition can affect different areas of the body, including the:

• Skeleton, which includes bone and connective tissues such as ligaments, tendons, and cartilage.
• Eyes.
• Heart and blood vessels, including arteries and valves inside the heart.
• Skin.
• Lungs.

Treatment varies depending on the area of the body affected and may include medications, other treatments, and surgery to manage the condition and its complications. Research and advances in treatments and surgeries allow people with Marfan syndrome to live long, productive lives.

What happens in Marfan syndrome?

Everyone has fibrillin-1 protein, which helps make elastic fibers in connective tissue. Fibrillin-1 also affects another protein in your body, transforming growth factor-beta (TGF-beta), which helps control how cells function throughout the body. People with Marfan syndrome inherit a gene mutation that changes the amount of fibrillin-1 and the function of cells, which causes:

• Changes in the strength and performance of tissues throughout the body, including blood vessels, the heart, ligaments, tendons, and skin.
• Overgrowth of bones, making them longer than usual.

Symptoms of Marfan Syndrome

The symptoms of Marfan syndrome vary from person to person because connective tissue is found throughout the body. Some people have mild or just a few symptoms, while others can have more serious problems. Signs and symptoms may include:

• Arms, legs, fingers, and toes that are longer in relation to the rest of the body.
• Chest wall (sternum) that caves in or sticks out.
• Curvature of the spine.
• Flat feet.
• Headaches.
• Heartbeat that feels like it is skipping a beat, fluttering, or beating too hard or too fast.
• Highly arched roof of the mouth (palate) that can lead to crowding of teeth.
• Loose joints.
• Long, narrow face.
• Low back pain and numbness in the legs.
• Shortness of breath due to changes in the lungs or heart.
• Stretch marks on the skin.
• Vision changes, such as blurry vision and extreme nearsightedness.

Because Marfan syndrome affects different areas of the body, other problems and complications can develop, including:

• Enlargement (aneurysm) of the main artery in the body (aorta), which happens when the wall of the aorta weakens and bulges. It is a life-threatening emergency if the wall of the aorta tears or ruptures.
• Cataracts, which are cloudy areas in the lens of the eye.
• Dural ectasia, which happens when the tissue that surrounds the spinal cord weakens and stretches.
• Ectopia lentis, which happens when the lens of the eyes shifts, often leading to changes in vision.
• Heart valve floppiness and leaking, which happens when one of the valves inside the heart is not working properly. If the leak is significant, it can make your heart work harder and affect its ability to pump blood.
• Hernia, which happens when tissue pushes through the weakened wall of the abdomen or pelvis.
• Pneumothorax, which happens when air leaks out of the lung into the chest cavity.
• Retinal detachment, which happens when the nerve layer in the back of the eye is pulled away from its normal position.
• Sleep apnea, which happens when the upper airway becomes blocked many times during sleep, reducing or completely stopping airflow. 

Causes of Marfan Syndrome

A mutation or change in the fibrillin-1 (FBN1) gene causes Marfan syndrome. People with Marfan syndrome generally inherit one normal copy of the FBN1 gene from one parent and one abnormal copy of from the other parent. One abnormal copy of the FBN1 gene is sufficient to cause Marfan syndrome, meaning that an affected child would inherit the condition from an affected parent. 

About one-quarter of people with Marfan syndrome have a new change in the FBN1 gene, meaning that neither parent is affected and that they are the first person in their family to have the condition. This is a so-called “dominant” mode of inheritance. A person with a dominant mutation has a 50% chance (1 in 2) of passing on the disorder to each of his or her children.