SCIENCE / MEDICINE : Hopes Raised in Battle Against Rare and Debilitating Marfan Syndrome
An abnormality in the body’s connective tissue may account for the debilitating and potentially deadly complications of a rare disorder known as Marfan syndrome, scientists reported last week.
The new finding may one day enable physicians to more accurately diagnose the syndrome in patients who only have some of the symptoms. Currently, physicians use family history and clinical observations to make a diagnosis.
Roughly one in 10,000 Americans has the inherited disorder, including a number of well-known athletes. The syndrome can weaken areas of the heart, blood vessels, lungs, bones, skin and eyes.
Marfan typically strikes people who are tall and thin, with long arms, fingers and toes and extremely flexible joints. On the average, the life expectancy of Marfan patients is decreased by one-third because of a dangerously weak and enlarged aorta--the main artery that funnels blood from the heart throughout the body. If the defect is not corrected it can be fatal.
Scientists have long debated the causes of Marfan syndrome and recently ruled out collagen or elastin, two components of connective tissue, as suspected culprits.
The new research suggests that a decreased amount and distribution of the protein fibrillin may explain the characteristic symptoms of the disease, researchers report. Fibrillin is one of the building blocks of microfibrils--slender, threadlike structures that make up the framework upon which connective tissue forms.
“We think that we’re getting closer to finding the basic defect in the production, assembly and strength of microfibrils (in Marfan patients),” said Dr. David Hollister, a medical geneticist at the University of Nebraska Medical Center and co-author of the report in the New England Journal of Medicine. “Microfibrils may not be as strong as they should be and stretch abnormally.”
Researchers examined skin samples from 27 patients with Marfan syndrome, 25 patients with other inherited connective tissue disorders and 13 healthy controls.
The scientists noted fibrillin deficiencies in 24 of 27 patients with Marfan syndrome, while 19 of the 25 patients with other connective tissue disorders and all 13 healthy subjects had normal amounts of fibrillin, Hollister said.
When skin cells of the Marfan patients were grown in the laboratory, 90% showed a fibrillin deficiency, the researchers said. Such a deficiency may result in an inadequate connective tissue framework, which in turn accounts for the characteristic symptoms of the disorder, Hollister said, but he cautioned that such a link has yet to be shown conclusively.
“It’s the most promising lead we have had to date,” said Dr. David Rimoin, director of the Medical Genetics Birth Defect Center at Cedars-Sinai in Los Angeles.
However, until the gene for fibrillin is isolated, it’s not possible to determine with certainty that the fibrillin deficiency causes the syndrome, he said.
Olympic volleyball player Flo Hyman and University of Maryland basketball player Chris Patton were among a number of athletes who died from the disorder in recent years when their aortas burst.
