Guide to Connective Tissue Disease (Including Marfan Syndrome)

Connective tissues are tissues throughout the body that support and bind cells together. Containing proteins such as collagen and elastin, connective tissues can be injured or inflamed as a result of inherited diseases, autoimmune diseases, and environmental exposure. Because connective tissue is located through the entire body, connective tissue disorders can affect many parts of the body including the bones, eyes, skin, nervous system, and lungs. Diseases such as the four described below affect the wall of the aorta, and its weakening increases the risk of aortic aneurysm and dissection.

Connective tissues significantly affect the aorta because the aorta is exposed to high shear stress, or pressure from the constant flow of blood. The aorta is a very well designed pipe that must convert chaotic flow into an organized stream. Imagine people leaving a sporting event or a concert: there is initial chaos, but eventually lines form at the exit and we proceed out the door. In much the same manner, two sites of chaos exist in the aorta. The first is at the aortic root, where blood shoots out of the heart and must be "corralled" into an organized manner. This active changing of the chaotic energy to organized flow requires strength. If the strength layer of the aorta is dysfunctional, the stress my internally break the aorta (a type A Dissection). The second site of chaos is at the end of the aortic arch, where blood must loop around and head downwards to supply to the abdomen and legs. The turn that the blood makes in the aortic arch is also a very chaotic and energetic phenomena. Consequently, the aorta may tear at this juncture as well (a so-called type B Dissection).

Many patients do not know that they may have an inherited condition. We work closely with the Division of Clinical Genetics at Columbia University to evaluate patients for the presence of connective tissue disorders. Patients who receive treatment at the Aortic Surgery Center and are known (or found) to have a connective tissue disorder such as Marfan syndrome, Ehlers-Danlos, or amyloidosis may be referred to the Division of Clinical Genetics. Moreover, all patients who undergo aortic surgery have samples sent to our pathology department. Any patient who exhibits evidence of connective tissue disruption or abnormal tissue consistency may also be referred for genetic testing upon further counsel.

Marfan Syndrome

Many have speculated that Abraham Lincoln had Marfan syndrome because of his height, his stooped posture, his long limbs, and certain other aspects of his appearance.Marfan syndrome is a genetic disorder that causes abnormal development of fibrillin, which is a component of the connective tissue. Although the disease may range from mild to severe, many patients with Marfan syndrome are very tall, thin, long-limbed, and loose-jointed. The most serious risks associated with the disease occur in the heart and aorta: weakness of the connective tissues puts patients with Marfan syndrome at risk for aortic aneurysm, heart valve disease, and aortic dissection. The reason is that there is a structural weakness in the wall of the aorta. The fibrillin helps maintain the integrity of the aorta, when it is exposed to high pressure. Its absence allows for aneurysms to develop and dissections to occur at early ages. It is important to realize that any change in size of an aortic root aneurysm in a patient with Marfan syndrome is an indication to meet with an aortic specialist. When surgery is indicated, often the operation can be performed as a valve-sparing procedure, with excellent long-term results.

Loeys-Dietz Syndrome

Loeys- Dietz syndrome (LDS) is another genetic disorder that shares similarities with Marfan syndrome. It affects proteins called transforming growth factor beta receptor 1 and 2, which are also part of the connective tissue found throughout the body. Some features of LDS overlap with Marfan syndrome, including aortic aneurysm or dissection, leakage of the mitral valve, loose flexible joints, and others. Other features of LDS are unique, such as arteries that twist and wind, aneurysms in arteries other than the aorta, widely spaced eyes, cleft palate, wide or split uvula, heart defects including atrial septal defect, bicuspid aortic valve, and many other features. These patients have very unstable aortic tissue and should have a surgical evaluation as soon as the diagnosis of Loeys-Dietz is made.

Bicuspid Aortic Valve

Bicuspid aortic valve is an abnormal formation of the aortic valve (the valve connecting the aorta to the heart). Approximately two percent of the population has a bicuspid valve. Often patients will have an awareness of its presence, as they were found to have a murmur during a routine physical examination. Bicuspid valves tend to wear out sooner than trilealfet valves, as blood passes through the leaflets with more turbulence. These valves also have a tendency to leak earlier than trileaflet valves. In about half of patients with bicuspid valve disease, an aortic root aneurysm begins to develop by age 30. The rate of growth is variable, but by age 30-50, many patients have developed an aneurysm of significant size. In these patients, the aneurysm develops not because of the valve, but because of a genetic defect in the ascending aorta. Any procedure to address the valve must also address the aortic aneurysm. 

Learn more about bicuspid valve disease.

Ehlers-Danlos Syndromes

Ehlers-Danlos Syndromes are a group of genetic disorders that share features such as easy bruising, loose and flexible joints, fragile skin, and weakened connective tissues. Among the subgoups of the syndrome is the vascular type, which is characterized by rupture of the arteries and bowel, clubfoot, and other manifestations. Other types of Ehlers-Danlos syndromes include those marked by hypermobility of the joints, skin laxity, fragile globe of the eyes, spine curvature, and other features. People with Ehlers-Danlos syndrome are at risk for aortic aneurysm because of weakening in the wall of the aorta.

Next Steps

People with connective tissue syndromes often require a team of specialists — such as pulmonologists, neurosurgeons, pain management specialists, and orthopedists — to meet their complex medical needs. The Columbia University Irving Medical Center Marfan Clinic serves as the first stop on that journey, with our team coordinating all of the care they need with other Columbia physicians. Learn more about the Marfan Clinic

To get started with the Marfan Clinic today, call us at (212) 326-8949 or fill out our online form. We’re here to help.