STORY BY

Deborah Mann Lake

There’s family and then there are cousins Pat Arthur and Leslie Goldsmith.

Thanks to Goldsmith’s information about their shared genetic likelihood of developing a fatal aortic aneurysm, Arthur was tested for the gene through a study at The University of Texas Medical School at Houston.

He learned he was already living on borrowed time.

She saved my life,” says Arthur, 58. “Being able to participate in the registry gave me the opportunity to schedule the surgery to correct it and not have to do it in an emergency situation.”

The aorta is the main blood vessel leading out of the heart and supplies blood to the rest of the body. Some people develop a progressive degeneration of the aortic wall, leading to a bulging aneurysm, or to a dissection (a tear in the wall). Thoracic aneurysms tend to be without symptoms until a catastrophic dissection or rupture occurs.

Thoracic aortic disease is the 15th leading cause of death in the United States, killing up to 20,000 people a year. Famous victims include actor John Ritter (54 years old when he died) and the creator of Broadway hit, “Rent,” Jonathan Larson (who was 35).

Once the aorta begins to dissect, patients may have anywhere from minutes to hours before it ruptures. Even if properly diagnosed in the emergency room, emergency surgery to repair the dissection is risky.

But if caught early enough (commonly thought to be when an aneurysm is 5 centimeters or less) a surgical procedure to repair the weak portion or replace it with a Dacron graft has a high degree of success.

From the lab to the bedside

Researchers including Dianna Milewicz, M.D., Ph.D., professor and director of the Division of Medical Genetics at the UT Medical School, have identified some of the defective genes that cause the inherited form of the disease. This genetic form affects 20 percent of people with aneurysms and dissections. Through DNA testing on family members, such as Goldsmith and Arthur, early identification of those at risk has led to diagnostic imaging and ultimately to saving lives.

“We’ve come a long way. We’ve identified and mapped genes over the years and have a very well-established research program looking at the genetic basis for this disease. In addition, we have begun to understand how you use that information to manage the disease,” Milewicz says. “We want to take it one step further and discover the biological pathways to this disease, whether it’s people who carry mutated genes or those who don’t but still end up with this disease.”

To that end, Milewicz will use a new, $11.6 million grant to create the Clinically Oriented Research in Thoracic Aortic Aneurysms and Dissections in the Texas Medical Center. Funds for the center, which she will direct, come from a five-year grant from the National Heart, Lung and Blood Institute (NHLBI).

The grant will include three projects focusing on discovering biological pathways, the role of inflammation and the cause of aortic disease in people who do not have the familial form.

In Arthur’s case, the research into his affected gene, called TGFBR2, showed a disturbing trend. That information was relayed to Arthur’s surgeon, Hazim Safi, M.D., professor and chairman of the Department of Cardiothoracic Vascular Surgery at the medical school.

“I was working with a cardiologist to watch the aneurysm,” says Arthur, whose father died of an aortic aneurysm at age 59. “Last Thanksgiving, I went to see Dr. Safi and he said some of the evidence Dr. Milewicz had discovered highly suggested surgery because in our genetic group, there had been a number of spontaneous ruptures. In this genetic group, the threshold was lower, 4 to 4.5. I was at 4.2, so I went ahead and had it done.”

A dedicated cyclist, Arthur had surgery last December and was riding again in late February. “I also rode in the MS 150 in April and I’m riding to San Antonio in September.”

A family tree of life

Arthur also has had his 10-year-old daughter tested and she does not carry the gene abnormality.

Goldsmith, 45, who discovered her enlarged aorta in a routine medical exam five years ago, lost her mother when she was just 3 weeks old.

“We think now it was an aortic aneurysm. She just collapsed. They did an autopsy and said she died from cardiomyopathy, from the aortic valve separating,” Goldsmith says.

Goldsmith’s maternal grandfather was one of Arthur’s uncles. In that generation, seven of 10 siblings either had evidence of an aneurysm or died from the disease, Arthur says. Other members of their family have been tested, but not all.

“Anyone who has the potential at all to have the gene needs to be checked in no uncertain terms,” he urges. “I’m a bike rider and I’ve always been in good shape. But you can’t outrun the gene.”

UPDATED: 9-06-2006

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