Marfan Syndrome

Marfan syndrome is a medical condition that affects the entire body; specifically the connective tissues. Connective tissue is the “glue” that holds cells together. It is found in the joints, eyes, heart, blood vessels, lungs, bones, and in the membrane covering the brain and spinal cord.

Marfan syndrome can affect both men and women of any race or ethnic group. It is estimated that 1 in 5,000 people have Marfan syndrome. The majority of affected individuals inherit the condition from one of their parents, however, some people are the first in their family to have Marfan syndrome. Marfan syndrome is inherited as an “autosomal dominant” condition. This means that someone with Marfan syndrome has a 50% chance to pass the syndrome on to their children. The genetic test for Marfan syndrome is available at most centers but is not routinely covered by insurance.

What Causes Marfan Syndrome?

A change in DNA structure causes an abnormality (mutation) in one of the genes that is responsible for the production of certain proteins, which are a key part of the connective tissue. The abnormal gene that causes Marfan syndrome is the FBN1 gene on chromosome 15 that encodes for the protein, fibrillin-1. In patients with Marfan syndrome, the FBN1 gene is abnormal, which causes the cells in the body to either not produce enough fibrillin or produce abnormal fibrillin. As a result, the connective tissue is not properly formed, leading to the changes or symptoms associated with Marfan syndrome.

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How Is Marfan Syndrome Diagnosed?

Marfan syndrome is diagnosed by using specific criteria. The criteria represent a set of guidelines which have been established to help physicians and other healthcare providers determine whether a patient has Marfan syndrome. These guidelines are based on clinical features seen on physical exams, as well as information obtained from the family history, echocardiogram, eye exam, and/or genetic testing.

Your physician may recommend genetic testing to help diagnose Marfan syndrome. Genetic testing consists of obtaining a blood sample from your child to examine the DNA for the abnormal gene mutation that causes Marfan syndrome.

What Are the Symptoms of Marfan Syndrome?

Many children with Marfan syndrome do not complain of any symptoms. However, children who have eye involvement may complain of having difficulty seeing far or have blurry vision. Other symptoms may include back or joint pain.

Physical Signs

The Skeleton: People with Marfan syndrome often have a tall, thin body build with long arms and long legs. They are often quite flexible or have “loose” joints. They may be flat footed (pes planus) or have an inward rotation (pronation) of their feet. Many affected individuals have curvature of the spine (scoliosis), an indentation of their chest (pectus excavatum), or a protrusion of the chest (pectus carinatum). The roof of the mouth (palate) is usually high and narrow with crowding of the teeth. The lower jaw may recede, making it appear as though the child has an overbite. The face may be long and narrow.

The Eye: The lens of the eye is responsible for focusing vision on particular objects. The lens is held in place by tiny muscles. In people with Marfan syndrome, these tiny muscles are more “stretchy” than normal, which subsequently allows the lens to move out of place from the center of the eye. This process is called lens dislocation and occurs in more than half of individuals with Marfan syndrome. It can be difficult to diagnose lens dislocation by just looking at the eye, therefore eye doctors (ophthalmologists) must put special drops in the eye and examine the eye with a special microscope to determine whether the lens is out of place.

People with Marfan syndrome are also more likely to develop cloudiness within the lens of the eye (cataract) and tend to do so at earlier ages than normally expected. They are also at risk for developing tears or holes in the retina (retinal detachment). A retinal detachment is a medical emergency and needs to be treated as soon as possible. If treatment is delayed or not obtained, permanent damage to the eye causing partial loss of vision or complete loss of vision in the eye may result.

Symptoms of a retinal detachment include sudden appearance of “floaters” in the eye, flashes of light or a shadow appearing over part of the vision. To reduce the risk of a retinal detachment, people with Marfan syndrome should avoid high impact activities such as boxing, football and diving.

The Heart and Aorta: Connective tissue is present in the heart muscle, valves and blood vessels, including the aorta. Approximately 75% of patients with Marfan syndrome have a “floppy” mitral valve (prolapse). In patients with mitral valve prolapse, the valve can leak, allowing blood to flow back across the valve. This is usually well tolerated by most patients, however, over time it may progress and cause a decline in heart function and/or abnormal heart rhythms to develop. If this occurs, patients usually require an open heart surgery to either fix or replace the mitral valve. In a very small percentage of patients with Marfan syndrome, the heart function may decline even if the mitral valve is functioning properly.

The aorta is the largest blood vessel in the body and is also affected by Marfan syndrome. The aorta is made up of three separate layers: the intima, media and the adventitia. The middle layer (media) is elastic and is the layer that is affected most by Marfan syndrome, making it weaker than a normal aorta.

Every time the heart beats, there is pressure or stress that occurs on the aortic wall. Over years, this stress or pressure causes the aorta to stretch (dilate) and eventually forms an aortic aneurysm. If an aneurysm forms, there is an increased risk of an aortic dissection (tear) to occur, which is a life-threatening medical emergency. Symptoms of an aortic dissection include chest pain radiating to the neck or back, difficulty breathing, dizziness or lightheadedness, and passing out. If this happens, call 911 immediately, as this represents a life-threatening emergency.

The Lungs: Patients with Marfan syndrome are at risk for developing collapse of the lung (pneumothorax). This can occur spontaneously or from blunt trauma to the chest. Symptoms of pneumothorax include difficulty breathing and chest pain.

Some patients with Marfan syndrome can have disturbed breathing during their sleep. This may occur due to a variety of reasons, including “floppy” airways, an abnormal palate and chest wall deformities, which may cause the airway to collapse or narrow during sleep.

The Nervous System: The central nervous system is made up of the brain and the spine, which is contained within a membrane called the dura. The dura is also composed of connective tissue, and therefore, also stretches over time. This most commonly occurs at the bottom of the spine and can result in pain caused by pressure on the bones of the spine.

Other Body Systems: There is an increased incidence of hernias in the groin (inguinal hernias) in patients affected by Marfan syndrome. It may also take a longer time for cuts or skin wounds to heal.

There is no cure for Marfan syndrome at this time. However, medications may be used to decrease the force with the heart pumps into the aorta to decrease the stress on the walls of the aorta. These medicines are called beta-blockers which are also used to treat high blood pressure. In addition, strenuous exercise, some competitive sports and contact sports may be restricted to also reduce injury to the aorta. If valve abnormalities are found, antibiotics may be prescribed around the time of surgical or dental procedures to prevent endocarditis.

How Is Marfan Syndrome Treated?

People affected with Marfan syndrome should be followed by physicians familiar with the condition and its effect on all body systems. Frequently this is accomplished by a specialized team of physicians including a cardiologist, ophthalmologist, orthopedic surgeon and geneticist. Additional specialists may also be requested to participate in care as needed. At a minimum, patients should be seen on a yearly basis, unless more frequent follow-up is recommended by your healthcare provider.

There is no cure for Marfan syndrome at this time. However, medications are used to help slow the progression of the aortic dilation over time. Several types of medications can be used, which include beta blockers, angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors. In addition, strenuous exercise, weight lifting, competitive sports and contact sports may be restricted. If valve abnormalities are found, antibiotics may be prescribed around the time of surgical or dental procedures to prevent infections within the heart (endocarditis).

What Are the Long-term Effects of Marfan Syndrome?

The life expectancy for someone with Marfan syndrome is similar to that in the general population as long as they receive frequent surveillance and appropriate medical care. Medical and surgical treatments continue to improve, offering patients improved

The life expectancy for someone with Marfan syndrome is similar to that in the general population as long as they receive frequent surveillance and appropriate medical care. Medical and surgical treatments continue to improve, offering patients improved quality of life compared to several years ago.

Women with Marfan syndrome, in general, can become pregnant safely, however, they should be under the care of a cardiologist as well as an OB/GYN that is experienced in the care of patients with this connective tissue disorder. If possible, it is best to talk to your doctors prior to becoming pregnant so that careful planning can be done prior to the pregnancy. If either parent is affected by Marfan syndrome, there is a 50:50 chance that the child will have Marfan syndrome. Because of variability in the expression of the Marfan gene, it is impossible to predict how severely the child will be affected.

The most serious problems with Marfan syndrome involve the cardiovascular system. Patients with Marfan syndrome can develop aortic aneurysms, which can lead to an aortic dissection (tear) and/or rupture, which are life-threatening medical emergencies. With close monitoring by a cardiologist, patients can be referred for elective surgery to replace the aorta when the aorta measures approximately 5 cm. Having an elective surgery to replace the aortic root can decrease the risk of having an aortic dissection. Surgery should be conducted at a hospital that is experienced in treating patients with Marfan syndrome.