Marfan syndrome

Definition

Marfan syndrome (or Marfan's syndrome) is an inherited disease that affects the connective tissue within the body. This results in a variety of skeletal deformities, as well as problems with the heart and the blood vessels (the cardiovascular system).

Description

Marfan syndrome is known to be a dominant genetic disorder, which means that a person needs to inherit only one defective gene in order to actually have the syndrome. In addition to those cases of Marfan's which are clearly inherited, 20% of all Marfan's patients have no family history of the syndrome. It is believed that these patients have undergone a spontaneous genetic mutation leading to the syndrome. Interestingly, one risk factor for Marfan syndrome (in a family where Marfan's is not already an inherited disorder) is an elderly father. Marfan syndrome is said to have variable expression, meaning that either all, or only a few, of the classic signs of Marfan syndrome may occur in any given patient.

The biochemical problem which results in Marfan syndrome has not been well defined. The group of tissues affected by Marfan syndrome are called the connective tissues. These are tissues that are made of fibrous components, and they provide structural support for other body tissues. Included in the group called connective tissues are bone, cartilage, fat tissue, lymph tissue, and blood. The current belief is that the affected gene results in an abnormality in a protein called microfibrillin; and this protein is responsible for certain structural characteristics of connective tissue throughout the body.

Causes & symptoms

Typically, a person with Marfan syndrome appears quite tall and thin, particularly when compared with other members of the same family. The patient's arms are proportionally quite long, compared to their stature, and their fingers are also long and thin, termed "arachnodactyly" (arachno means spider-like, while dactyly refers to fingers). The patient's chest wall may protrude out, or be sunken in, while the spine often has an abnormal curvature. The patient's joints are usually loose, and may be able to be bent in the wrong direction (double-jointedness). Muscles are often smaller than normal, and hernias (protrusions of internal organs through weak areas in muscle) are frequent in Marfan's patients. Several lung problems are common, including the tendency to spontaneously suffer a collapsed lung (pneumothorax).

A variety of eye abnormalities usually accompany Marfan syndrome, with extreme nearsightedness and dislocation of the lens the most common manifestations. Glaucoma, cataracts, and retinal detachment also occur more frequently than normal.

The most serious and potentially life-threatening complications of Marfan syndrome occur due to the involvement of the heart and blood vessels. The mitral valve (the gateway out of the heart for all the blood entering the body's circulation) is frequently abnormal, resulting in a heart murmur. The wall of the aorta (the major artery leaving the heart) is prone to stretching (dilation). Over time, the aorta becomes increasingly weak, leading to bulging (called an aneurysm) and possible rupture. Such ruptures lead to heavy, uncontrollable bleeding into the body (severe hemorrhage), and almost certain death.

Diagnosis

There are no laboratory tests to aid in the diagnosis of Marfan syndrome, so diagnosis relies on the identification of some cluster of the classic signs of Marfan's occurring in a particular patient. Of course, suspicion is greater in a family where other members are already known to have Marfan syndrome. The particular type of lens dislocation common in Marfan syndrome is so rare outside of Marfan's, that this finding alone should lead to a high degree of suspicion. Diagnosis is crucial, because an individual with Marfan syndrome must receive regular, careful evaluation of the cardiovascular system (especially the aorta), in order to avoid the potentially fatal complication of a ruptured aneurysm.

Treatment

There is no treatment for Marfan syndrome itself that can reverse the overall connective tissue defects. Each manifestation of the syndrome needs to be addressed individually (braces and physical therapy for the spinal curvature, occasional lens removal for the lens dislocations, etc.). For girls who have grown quite tall, and have cosmetic concerns about any further height, hormonal medications have been given to initiate an early puberty, so that growth stops sooner and adult height is closer to normal.

As stated previously, the most important problems to follow closely are those affecting the heart and aorta. Some medications seem to be somewhat useful in slowing the stretching of the aorta, although surgical replacement of part of the aorta is sometimes necessary, as may be replacement of the defective mitral valve.

Prognosis

Careful monitoring of Marfan's patients, along with advice to avoid stress (physical, emotional, and the stress of pregnancy) has helped to increase the expected life span of Marfan's patients well beyond the age of 30 or 40 years, which was once the typical age of death.

Prevention

While prevention is not totally possible, it is important that any couple who is aware of a family history of Marfan's receive careful genetic counseling prior to having a baby. Counseling should provide such a couple with information on which to base their child-bearing decisions, including the fact that the child of a parent with Marfan syndrome has a 50% chance of having Marfan's.

Key Terms

Aneurysm

A weakening in and bulging out of the wall of a blood vessel. Rupture of such an aneurysm can be fatal, or can result in permanent disabilities, depending on where in the body the aneurysm is located, and how catastrophic the bleeding resulting from the rupture is.

Aorta

The major blood vessel leaving the heart and carrying blood to numerous other smaller vessels which branch off and deliver blood to the entire body.

Cardiovascular system

The body system which includes the heart and the blood vessels.

Connective tissue

A biochemically distinct group of the body's tissues, which provide structural support for other body tissues.

Mitral valve

A one-way gateway for blood leaving the heart, which is located at the entrance to the major blood vessel leaving the heart (the aorta).

Further Reading

For Your Information

Books

• Cecil Essentials of Medicine, edited by Thomas E. Andreoli. Philadelphia: W.B. Saunders Company, 1997.
• Procknop, Darwin J., et al. "Marfan Syndrome." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

  Organizations

• National Marfan Foundation. 382 Main Street, Port Washington, NY 11050. (800) 8-MARFAN. http://www.marfan.org.

Gale Encyclopedia of Medicine. Gale Research, 1999.