Marfan syndrome

Marfan syndrome is a disorder of the connective tissue, which provides strength and flexibility to most structures in the body. As a result, this syndrome affects most organs and tissues, especially the skeleton, lungs, eyes, heart, and aorta, which is the artery that distributes blood from the heart to the rest of the body.

Symptoms of Marfan syndrome can vary greatly in intensity, onset, and rate of progression. Common physical features include being tall and thin, with elongated arms and legs, as well as fingers and toes. Affected individuals may also have extraordinarily flexible joints, a long and narrow face, small jaw, clenched teeth, an abnormal curvature of the spine (scoliosis), and sunken (pectus excavatum) or protruding chest (pectus carinatum), which can lead to breathing problems, as it does not allow the chest to expand normally. More than half of all people with this syndrome have vision problems in one or both eyes because the lens is off-center and most have some degree of myopia and astigmatism. They are also at an increased risk of retinal detachment, cataracts, and glaucoma (increased pressure inside the eye), and often suffer from these problems at a younger age than normal.

Adults with this disorder may develop sleep apnea (small pauses in breathing during sleep), pulmonary emphysema, and collapsed lungs.

Most people with Marfan syndrome have abnormalities in the heart and aorta which produce the most severe symptoms. This syndrome weakens and progressively stretches the aorta, which can eventually lead to a rupture in its lining if left untreated, and can result in sudden death. Leaks in the heart valves that control blood flow through the heart can cause shortness of breath, fatigue, and palpitations.

There is no cure for Marfan syndrome, but advances in the prevention and treatment of the resulting symptoms have greatly improved life expectancy, which is approximately 70 years. A multidisciplinary team of doctors, including among others a cardiologist, should treat this disorder because it affects multiple organs. Beta-blockers are often used to reduce heart problems by reducing the heartbeat’s strength and frequency to prevent rupture of the aorta. In some cases where medication is not enough, surgery is usually performed to repair the aorta and/or a defective heart valve. Braces or surgery may be used to treat scoliosis or chest deformities, while early treatment of eye problems such as glaucoma or cataracts can greatly reduce vision problems.

Marfan syndrome is caused by mutations in the FBN1 gene, which affects the formation of fibrillin-1, a vital protein in connective tissue found in bones, lungs, ligaments, and the lens of the eye or aorta.

Together with other proteins and molecules, this protein participates the formation of microfibril networks. These networks are part of the extracellular matrix of tissues and provide strength and flexibility to connective tissue. These microfibrils also contain molecules called growth factors, which must be released at the right time to control the growth and repair of tissues and organs in the body. Mutations in this gene cause a small amount of fibrillin-1 to be produced or defective, which causes that the microfibril networks do not form correctly and no adequate release of growth factors occurs, causing the characteristic symptoms of this disorder.

Marfan syndrome occurs globally in 1 in 5,000 people and affects both men and women of all racial and ethnic groups.

This syndrome follows an autosomal dominant pattern of inheritance, which means that a single copy of the altered gene is enough to cause the disease. Children of an affected person have a 50% chance of inheriting the mutation and, therefore, suffering from the disease.

About 20-25% of Marfan syndrome cases are caused by a spontaneous mutation, which occurs when the parents do not suffer from the syndrome and there is no family history of the disease, and the mutation has formed spontaneously.

Affected individuals do not present the same clinical manifestations, or at least not with the same severity. This phenomenon is called variable expression, meaning that the mutated gene manifests differently in each patient.

SIMA – Association of People Affected by Marfan Syndrome

SIMAC – Association of people affected by Marfan syndrome in Catalonia

The Marfan Foundation – National Marfan Foundation