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 veins, 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 a fibrillin-1 protein, which makes elastic fibers in connective tissue. Fibrillin-1 also affects another protein in your body, transforming growth factor-beta (TGF-beta), which helps control how the body grows and develops. People with Marfan syndrome inherit a gene mutation that changes how the body uses fibrillin-1, leading to excess growth factors, which causes:

• Tissues in blood vessels, the heart, ligaments, tendons, and cartilage to stretch more, making them weak.
• 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. Symptoms may include:

• Abdominal pain.
• Arms, legs, fingers, and toes that are much longer in relation to the rest of the body.
• Chest 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 mouth 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:

• Aneurysm of the aorta, which happens when the wall of the aorta weakens and bulges. It is a life-threatening emergency if the wall of the aorta ruptures.
• Cataracts, which are cloudy areas in the lens of the eye.
• Dural ectasia, which happens when the tissue that wraps and protects the spinal cord and brain stretches and weakens.
• Ectopia lentis, which happens when the lens of the eyes shifts, leading to changes in vision.
• Glaucoma, a group of eye diseases that can cause vision loss and blindness by damaging a nerve in the back of your eye.
• Heart valve 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 in the abdomen, which happens when tissue pushes through the weakened wall of the abdomen.
• Pneumothorax, which happens when a section of the lung collapses because the alveoli (tiny air sacs in the lungs) burst.
• Retinal detachment, which happens when the retina is pulled away from its normal position at the back of the eye.
• Sleep apnea, which happens when the upper airway becomes blocked during sleep, leading to breathing that starts or stops. 
• Weakened or stretched aorta, which is the large artery that carries blood from the heart to the rest of the body. Damage to the aorta increases the risk for serious heart problems or even sudden death.

Causes of Marfan Syndrome

A mutation or change in the fibrillin-1 (FBN1) gene causes Marfan syndrome. People with Marfan syndrome inherit one normal copy of the FBN1 gene and one abnormal copy of FBN1 from their parents. The abnormal copy of the gene is stronger or “dominant” over the normal copy of the gene and causes Marfan syndrome. This is 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.

Some children are born with the syndrome, even though there is no family history of the disorder, because of a new mutation in the FBN1 gene.