From Our 2006 Archives

New, Deadly Relative of Marfan's Syndrome Discovered

By Ed Edelson
HealthDay Reporter

WEDNESDAY, Aug. 23 (HealthDay News) -- A connective tissue disease that is a molecular cousin of Marfan's syndrome, but even deadlier, has been discovered by an international team of medical researchers.

The disease has been christened Loeys-Dietz Syndrome, after researchers Dr. Bart L. Loeys of the Center for Medical Genetics in Ghent, Belgium, and Dr. Harry Dietz, of Johns Hopkins University School of Medicine in Baltimore. Like Marfan's syndrome, it is caused by a genetic flaw that weakens tissue and can kill suddenly by rupturing the aorta, the main artery of the heart.

Perhaps 200,000 Americans have Marfan's syndrome. They are monitored carefully for signs of aortic trouble, with aggressive surgery often recommended. The incidence of the new condition is unknown, "but since we published earlier this year, two or three cases are being diagnosed every week," said Loeys, who is assistant chief of clinics at the Ghent facility. "The patients we see now might be the tip of the iceberg."

"We were seeing one new family a week," said Dietz, a professor in the Hopkins Institute of Genetic Medicine. "Just people who came in for an evaluation because someone had an aneurysm or someone died."

A paper in the Aug. 24 issue of the New England Journal of Medicine, with Loeys and Dietz listed as lead authors, describes the molecular and physical features of the disease in 52 families. The outstanding physical condition, Loeys said, is that the weak spots in the blood vessels that occur in the root of the aorta of Marfan's patients are found "in all branches of the aorta and also in the brain."

Therefore, patients with the newly discovered condition require even more careful monitoring than those with Marfan's syndrome, Dietz said. "There is one important distinction, that in this syndrome aneurysms can happen throughout the body, in the chest and the abdomen," he said.

A common thread in the two conditions is overactivity of a molecule called transforming growth factor beta (TGF-beta), which Dietz describes as "a molecule that tells cells how to behave, when to divide, where to migrate, when to die." In Marfan's syndrome, TGF-beta is overproduced. In Loeys-Dietz syndrome, the receptor that allows the molecule to enter cells is deformed, so more TGF-beta remains active.

The result is a failure of connective tissue to hold together, with a major threat to the integrity of the aorta in Marfan's syndrome and many blood vessels in Loeys-Dietz syndrome.

While there is no drug treatment currently for Marfan's syndrome or Loeys-Dietz syndrome, research at Hopkins has raised hopes about losartan, a drug used to treat high blood pressure. In early animal studies, losartan showed an ability to inhibit TGF-beta activity and prevent aneurysms, Dietz said.

"It has great promise, but the final decision will depend on the results of future studies," Dietz said.

SOURCES: Bart L. Loeys, M.D., Ph.D, assistant chief of clinics, Center for Medical Genetics, Ghent, Belgium; Harry C. Dietz, M.D, professor, Johns Hopkins Institute of Genetic Medicine, Baltimore; Aug. 24, 2006, New England Journal of Medicine

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