Inquirer Staff Writer

Theirs is not the kind of medical history anyone wants.

The grandchildren of George Melling hope others can learn from the trail of death and damaged hearts that runs through their family tree.

Four cousins - the children of two of George's daughters - died decades ago when their hearts stopped suddenly. Two were teenagers; another was 22 years old.

When one of the mothers developed heart problems, a Johns Hopkins University doctor began looking for inherited heart defects in other family members and readily found them.

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Their case was so interesting - often not a comforting word in medical circles - that the genetic tests of the Philadelphia family of a third sister, Agnes McDermott, became the subject of a groundbreaking study in the New England Journal of Medicine in 1991. Seven of her 15 children had one of the mutations that causes hypertrophic cardiomyopathy, a disease of the heart muscle.

Last month, one of those children, Paul McDermott of Havertown, and his cousin Mary Wiedel, of Ellicott City, Md., both had heart transplants at the Hospital of the University of Pennsylvania. Paul's oldest sister, Rosemary, paved the way almost five years ago when she also had a transplant at Penn. At that point, she said, "My heart was garbage."

At a family gathering, the 6-year-old daughter of a cousin who died in his 50s told her, "I'm going to die early because I have a heart like my daddy."

Rosemary McDermott, a former nun who became a teacher and then a government worker and a lawyer, decided she had to give that girl hope. "By golly, I'm going to have the transplant and show that little girl you can live to be 100 even with a bad heart," she said.

Now 70, she became a judge in Maryland after the transplant and routinely alternates an hour of cardio work at the gym with weightlifting.

Over the years, the Melling descendants have worked with researchers at Johns Hopkins and Harvard Universities. Several members are now seen at the two-year-old Familial Cardiomyopathy Program jointly run by the Penn health system and Children's Hospital of Philadelphia, the only one of its kind in the tristate area.

They wanted to know who was at risk because medications and expert care can delay problems. Defibrillators reduce the chance of sudden death. The family also wanted to help doctors learn more about their condition.

"I raise my hand for any study . . . to give them good data to make advances," Paul McDermott, a tall, trim 58-year-old, said last week. His living room was filled with the Christmas decorations he'd missed while waiting for a new heart in the hospital in December, too weak then to even brush his teeth. Already, he's walking two miles a day. "I didn't think it was ever going to help me personally."

Thomas Traill, a Johns Hopkins cardiologist, was among those who helped find the family's mutation. They have the most common genetic cause of hypertrophic cardiomyopathy, which affects 1 in 500 people. Most cases are inherited.

"We are very much in their debt," he said of the McDermotts and their cousins. "They've taught us a huge amount about the natural history of their particular mutation."

Cardiomyopathy comes in many forms. They can be inherited or caused by external factors, including the bad habits that lead to clogged blood vessels. There are no reliable numbers on how many have the condition, said Anjali Tiku Owens, who codirects the Penn-Children's program.

Hypertrophic cardiomyopathy, which causes the walls of the heart's pumping chambers to thicken, is usually genetic. It is the most common cause of sudden death in young athletes.

Dilated cardiomyopathy, in which the pumping chambers are abnormally large and weak, is the other common inherited form, Owens said.

The conditions are inherited in an autosomal dominant fashion, meaning offspring have a 50-50 chance of getting a parent's gene. If you didn't get the mutated gene, your kids are safe. So far, mutations of dozens of genes have been found to cause the heart disorders and "it is growing by leaps and bounds," Owens said.

Some people never have significant symptoms of cardiomyopathy. Some are killed by it and some develop symptoms in midlife. "It can come on at any time in your life," Owens said.

This means people may not know they have an inherited form of cardiomyopathy until it's too late. If a close relative has it, that's a clue you may need testing. Doctors recommend that adult family members be screened by EKG and echocardiogram every three to five years, and children every one to three years.

Lisa Salberg, chief executive officer and founder of the Hypertrophic Cardiomyopathy Association in Hibernia, N.J., said few families are screened properly. Many people go only once or resist going at all when they feel fine. "That has killed more people than I can tell you," said Salberg, who lost her sister and has had a stroke herself.

Salberg pushes for the formation of programs specifically for patients with hypertrophic cardiomyopathy. A new one opened last week at Morristown Medical Center, where her sister died.

Symptoms of hypertrophic cardiomyopathy include dizziness upon standing, breathlessness after eating or walking up inclines, chest pain, and palpitations. Owens said some young people with the condition are misdiagnosed with asthma.

Centers like hers, she said, take a four-generation family history. They look not only for sudden deaths, but also for heart failure and abnormal heart rhythms.

Traill said the Melling descendants had shown doctors that their type of hypertrophic cardiomyopathy looks different over time. In the young, the heart contracts with unusual strength to compensate for the thick walls. Doctors give medicines that lessen the contractions and warn patients not to engage in strenuous sports that involve quick starts, the time of greatest risk of blackouts and sudden death.

Over time, Traill said, the heart muscle becomes scarred and fibrous. Then patients need drugs that strengthen contractions.

Paul McDermott was an avid athlete in high school and college and played hours of basketball a day. He thought it was normal to feel as if a knife was twisting in his chest. Up until he "fell off a cliff" late last year, he continued to exercise, carefully.

He said the genetic results were a blessing for his family because they knew who could relax and who needed to be watched by doctors. After he read an article about genetic work on cardiomyopathy, he called the researcher at Harvard. Within days, she was in Philadelphia, where he had gathered the athletic, high-energy family for soup and blood tests.

Having to go repeatedly for heart scans had been "very emotional and gut-wrenching." When he learned that only one of his three children had the gene, it was a relief. He and his wife Nancy had been taking them for testing every year. "The genetics took that away," she said. "I found that to be fabulous."

At the time, Paul was feeling well enough that he wasn't worried for his son.

Owens said some couples now opt to have embryos tested for the mutations before implantation.

Mary Wiedel also wanted to confront the truth. (Not everyone in the family has.) "I'm a person of great faith and I felt like this was a blessing to know what we were dealing with," she said. None of her children inherited the gene. "That's where it stops, with me."

Paul's older sister Regina Smyth, 65, of Oreland, has had some symptoms and she has a defibrillator, but is hopeful she can avoid a transplant. Another affected sister has a defibrillator. Three other siblings have not yet had heart problems.

Wiedel is still struggling with some complications after surgery, but both Paul and Rosemary said it was remarkable to wake from their transplant and feel a normal heart beating.

"I was so excited I just wanted to rip the tubes out and run up the hall," Rosemary said. "Wow. Is this how normal people feel?"

She conceded that it had been tough to live with the knowledge that her heart would likely fail her. "My mother had it and we watched her die and we knew it was going to happen to us."

Both she and Paul think researchers will find an easier road for the next generation.

"I'm really optimistic that with the quantum leaps being made in science," Rosemary said, "they're going to be able to do something less traumatic than a heart transplant."


sburling@phillynews.com

215-854-4944

@StaceyABurling

www.inquirer.com/health_science

 

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