Marfan Syndrome
Marfan Syndrome
Marfan syndrome is a genetic disease that involves defects in the connective tissues of the body with the cardinal collection of abnormalities affecting the skeletal, ocular, and cardiovascular systems. It is inherited as an autosomal dominant disorder, meaning that inheriting only one defective gene from either the paternal or maternal side will lead to the disorder. Although the majority of mutations are inherited from one of the parents, approximately 25% of affected individuals develop Marfan syndrome as a result of a new mutation. The prevalence of the disease is about one in 10,000 persons, and the disorder is inherited with variable expression. This term means that each individual may have a different combination of the possible clinical features that characterize the disorder. There is no cure for the disorder.
Symptoms
There are a variety of skeletal deformities associated with the syndrome including disproportionately long limbs and digits, myopia (extreme near-sightedness), a chest deformity, joint laxity, and vertebral column deformities such as scoliosis. Dislocation of the lens of the eye represents a hallmark clinical feature. The most serious and potentially life-threatening complication of Marfan syndrome relates to abnormalities in the heart and blood vessels. The mitral valve (the gateway out of the heart for all the blood entering the body’s circulation) frequently billows backwards when the heart contracts. The wall of the aorta (the major artery leaving the heart) is prone to stretching and becomes increasingly weak, leading to bulging and susceptibility to rupture called an aortic aneurysm. Such a rupture leads to severe hemorrhaging (internal bleeding) and if untreated, death.
History
Former U.S. President Abraham Lincoln (1809–1865) was thought to have Marfan syndrome in that he manifested several key clinical features. However, it was not until after he died, in 1896, when French pediatrician Antoine Marfan (1858–1942) first described a specific cluster of skeletal abnormalities in a five year old girl who was thin, and had long limbs and abnormally long fingers and toes. Marfan compared the girl’s long digits to the legs of a spider, which gave the condition its medical name, arachnodacryly, from the Greek word for spider, arachne.
Marfan’s findings had been suggested 20 years earlier by an eye doctor in Cincinnati, Ohio, who described a tremor in the irises of a brother and sister with long limbs and exceptionally flexible joints—all subsequently shown to be characteristic symptoms of Marfan’s syndrome. Later, observers noted that Marfan’s patients also are often tall and thin, with a long and narrow face, and may have a curved spine and a protruding or sunken breastbone. Most serious, it was found that the heart valves in Marfan’s patients tend to leak, and the aorta—the body’s largest artery—tends to enlarge and develop aneurysms, weak spots that may suddenly and fatally burst.
In the 1950s, a large number of patients and their families were assessed and the clinical features of the syndrome were characterized. At the time the relationship between the abnormality of the aorta and the dislocated lens of the eye eluded physicians. It later became clear that both the ligaments of the lens and the lining of the aorta had a similar defect elucidated only after the candidate gene was discovered and its functional significance studied.
Cause and treatment
In 1991, researchers discovered that a defective gene on chromosome 15 causes the syndrome. The severity of the disease will vary depending on the type of mutation, which affects the production of a protein call fibrillin, which is a protein that plays a role in the characteristically elastic properties of connective tissue. As a result, individuals with the syndrome apparently have insufficient amounts tiny fibers, which provide strength and elasticity to normal connective tissue. The biochemical abnormality that leads to Marfan syndrome is not well understood. Biochemical defects are thought to involve the synthesis, secretion and
KEY TERMS
Aorta —The major blood vessel leaving the heart and carrying blood to numerous other smaller vessels that branch off and deliver blood to the entire body.
Connective tissue —A biochemically distinct group of the body’s tissues, which provide structural support for other body tissues. Examples of connective tissue include bone and cartilage.
Mitral valve —A one way gateway for blood leaving the heart, located at the aorta.
incorporation of fibrillin into connective tissue. Research is under way to identify the various mutations that cause the disorder.
There are no genetic tests available to help diagnose Marfan syndrome. A clinical geneticist might be more inclined to diagnose a patient with Marfan syndrome if there are other first-degree relatives that have a Marfan-like habitus. Without such an observation, skeletal involvement and at least two other systems affected by at least one major manifestation (for example, dislocated lens of the eye and the aortic abnormality) is required for a definitive diagnosis. It is also common that the wing-span, or the distance from one outstretched hand to another, is larger than the height. Early diagnosis is important so that the cardiovascular system can be carefully evaluated to prevent aortic rupture. Currently, there is no treatment for Marfan syndrome that can reverse the overall connective tissue defects. Each manifestation of the syndrome is addressed individually (eg., braces and physical therapy for the spinal curvature, occasional lens removal for the lens dislocations). Some medications seem to be somewhat useful in slowing the stretching of the aorta, although surgical replacement of part of the aorta or the defective mitral valve is sometimes necessary.
Patients of Marfan’s syndrome must be regularly monitored via echocardiography to check the size of the aorta and may need to be medicated with beta blockers, which reduce stress on the aorta by lowering the heart rate and contraction strength. The lifespan of a Marfan’s syndrome patient is shortened, with survival likely only into the sixties. The results of undiagnosed or unmonitored Marfan’s can be tragic, as in the case of Flo Hyman, a 6-foot-5-inch (about two meters) Olympic volleyball star who died of an aorta rupture while on tour; her Marfan’s was discovered only by autopsy.
See also Circulatory system; Gene mutation; Genetic disorders; Genetic engineering; Genetics.
Resources
BOOKS
Marfan Syndrome: Obstetric Issues. Port Washington, NY: National Marfan Foundation, 2004.
Nussbaum, Robert L., Roderick R. McInnes, Huntington F. Willard. Genetics in Medicine. Philadelphia, PA: Saunders, 2001.
Pveritz, Reed E., and Cheryll Gasner. The Marfan Syndrome. Port Washington, NY: National Marfan Foundation, 2001.
Rimoin, David L. Emery and Rimoin’s Principles and Practice of Medical Genetics. New York: Churchill Livingstone, 2002.
Robinson, Peter, N., and Maurice Godrey. Marfan Syndrome: A Primer for Clinicians and Scientists. Georgetown, TX: Landes Bioscience; New York: Kluwer Academic/Plenum, 2004.
PERIODICALS
McKusick, Victor A. “The Cardiovascular Aspects of Marfan’s Syndrome.” Circulation 11 (1955): 321–342.
OTHER
Doctor Zebra. “The Medical History of President Abraham Lincoln.” September 28, 2002. <http://www.doctorzebra.com/prez/g16.htm> (accessed November 30, 2006).
National Marfan Foundation (NMF). “Home page of NMF.” February 19, 2002. <http://www.marfan.org/nmf/index.jsp> (November 22, 2002).
Bryan Cobb