Marfan syndrome

Marfan syndrome is a disorder of the connective tissue. Connective tissue provides strength and flexibility to structures throughout the body such as bones, ligaments, muscles, the walls of blood vessels, and heart valves.

Marfan syndrome affects most organs and tissues, especially the skeleton, lungs, eyes, heart, and the large blood vessel that distributes blood from the heart to the rest of the body (the aorta). The signs and symptoms of Marfan syndrome vary widely in severity, timing of onset, and rate of progression. Affected individuals often are tall and slender, have elongated fingers and toes (arachnodactyly), and have an arm span that exceeds their body height. Other common features include unusually flexible joints, a long and narrow face, a highly arched roof of the mouth, crowded teeth, an abnormal curvature of the spine (scoliosis), and either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). About half of all people with Marfan syndrome have vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes, and most have some degree of nearsightedness (myopia). Clouding of the lens (cataract) may occur in mid-adulthood, and increased pressure within the eye (glaucoma) occurs more frequently in people with Marfan syndrome than in those without the condition.

Most people with Marfan syndrome have abnormalities of the heart and the aorta. Leaks in valves that control blood flow through the heart can cause shortness of breath, fatigue, and an irregular heartbeat felt as skipped or extra beats (palpitations). If leakage occurs, it usually affects the mitral valve, which connects two chambers of the heart, or the aortic valve, which regulates blood flow from the heart into the aorta. The aorta can weaken and stretch, which may lead to a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may cause the aortic valve to leak, which can lead to a sudden tearing of the layers in the aorta wall (aortic dissection). Aortic aneurysm and dissection can be life threatening.

Worldwide, the incidence of Marfan syndrome is approximately 1 in 5,000.

Mutations in the FBN1 gene cause Marfan syndrome. The FBN1 gene provides instructions for making a protein called fibrillin-1. Fibrillin-1 binds to itself and other proteins and molecules to form threadlike filaments called microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. Additionally, microfibrils hold molecules called growth factors and release them at the appropriate time to control the growth and repair of tissues and organs throughout the body. A mutation in the FBN1 gene can reduce the amount and/or quality of fibrillin-1 that is available to form microfibrils. As a result, growth factors are released inappropriately, causing the characteristic features of Marfan syndrome.

Some researchers believe that a small percentage of Marfan syndrome cases are caused by mutations in the TGFBR2 gene. These cases are called Marfan syndrome type II. Other researchers believe that TGFBR2 mutations cause a disorder that may have some Marfan-like features but is not Marfan syndrome. The TGFBR2 gene provides instructions for making a protein that transmits signals from the cell surface to other signaling molecules inside the cell. These molecules then relay signals to the nucleus to either turn on or turn off specific genes. Through this signaling process, the environment outside the cell affects activities inside the cell such as division and growth. Mutations in the TGFBR2 gene alter the signaling activity of the protein, which disturbs the growth and development of cells and tissues.

Read more about the FBN1 and TGFBR2 genes.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

At least 25 percent of classic Marfan syndrome cases result from a new mutation in the FBN1 gene. These cases occur in people with no history of the disorder in their family.