The Demon Gene: ‘A spectacularly horrible’ disease wreaks havoc with several generations of a Canadian family

Sat Jun 24 2006, National Post

By Margaret Munro

A lethal gene has cut a swath through Corey Winter’s family. It killed great-great uncles as young as 25, his great grandfather at 36 and his grandmother at 61. Uncles in their 30s and 40s, seemingly healthy men, suddenly collapsed and died.

The gene is now unleashing its horror in Mr. Winter’s generation, killing 20- and 30-year-olds. His cousin Elvis was raking up in front of his new house when he died at 28.

The first symptom that something was wrong was his last.

Mr. Winter has been there, seconds from death, his head spinning, about to black out. But his story has a much different ending. As he dropped to the ground, a device wired to his heart fired and zapped him back to life.

“Same thing as if you swallowed a stick of dynamite,” says Mr. Winter, 34, who has now experienced near-death followed by a lifesaving jolt more than a dozen times.

He is one of 97 Newfoundlanders who have been fitted with heart defibrillators as part of an ambitious effort to tame the gene that causes arrhythmogenic right ventricular cardiomyopathy, or ARVC.

Researchers say it is the worst genetic demon they have ever encountered.

There are plenty of awful genetic diseases, says Kathy Hodgkinson, a geneticist at Newfoundland’s Memorial University, co-leader of the research team. “But this one is so spectacularly horrible the way it takes off young people,” she says. “They are completely normal and then they drop dead.”

The gene is even more lethal than researchers envisioned when the project started almost a decade ago.

They now know 80% of men with the gene do not live to see 50. And the effort to save them is creating wrenching ethical problems.

A test can identify individuals who carry the gene, enabling them to opt for defibrillators that can save their lives.

But in some instances — including one where a mother refuses to tell her grown children they may have the gene — the researchers would have to break patient privacy and confidentiality rules to alert people in danger.

And that’s just one of the moral tangles.

The research team now has the ability, and inclination, to test boys in affected families when they are just 10 years old. The results could be both life-saving and traumatizing, possibly rendering young men with the gene unmarriageable, unemployable and uninsurable.

Mr. Winter and his wife Christine dread the day their two young boys go for testing. There is a 50/50 chance they carry the gene.

“To try to tell a child there might be something wrong with their heart,” says Mr. Winter. “I am really not looking forward to that.”

ARVC is not uncommon; it causes many of the 350,000 sudden cardiac deaths in North America each year. But the inherited variety in Newfoundland and Labrador strikes early, is particularly lethal and is common in a number of the region’s huge extended families.

The families have long known they have a problem — or “curse,” as some used to call it. Young people in the families have been dropping dead for generations — in the woods, out fishing — even, in the case of one 35-year-old, sitting in church, says Ms. Hodgkinson, who has spent years combing through the archives and detailed family histories that make Newfoundland and Labrador a dream for genetic researchers.

Doctors could not explain the premature deaths until the late 1980s, when pathologists took a close look at the hearts of some of the victims and recognized telltale signs of ARVC.

Investigators now believe people with the genetic disorder are born with normal hearts. But over the years the gene promotes growth of fatty and fibrous tissue in the heart. Eventually — and suddenly — the extra tissue triggers malfunctions that throw the heart out of rhythm. Death usually follows within minutes.

Sometimes, fainting spells warn of trouble. “But often the first symptom is heart arrhythmia and the person drops dead,” says Terry-Lynn Young at Memorial. “So the first symptom is death.”

Clusters of ARVC in Newfoundland families attracted gene-hunters from Germany and the U.S. in the 1990s. They took DNA from hundreds of people and searched for the gene, which, if found, might lead to treatment for many forms of cardiac arrhythmia. They didn’t find it.

Ms. Young is determined to track it down. She is a Newfoundland native lured back from Seattle and was recently awarded more than $9-million to set up a state-of-the-art gene lab at Memorial. She has made the quest for the gene a top priority as part of her work funded by the Canadian Institutes of Health Research and Genome Canada.

“I have got to find that gene,” said Ms. Young.

While the sleuths have yet to pinpoint the exact gene, she says they have narrowed the search to a specific chunk of DNA on chromosome 3, which is carried by people who die of inherited ARVC.

The scientists can follow the gene’s deadly path through 16 huge families — the largest has 1,200 individuals and goes back nine generations — and they suspect many more families are affected. They say the families appear to link back to a single ancestor who died in the 1700s, but not before passing on the gene to several sons and daughters.

Both sexes inherit the gene, but it is most lethal in males. Half of men with the gene die before their 40th birthday. Among women, 5% die by age 40 and 20% by 50.

To try to stop the carnage, the scientists have devised a test to identify people with the genetic fragment known to contain the gene. Dr. Sean Connors’ cardiac team in St. John’s has stitched defibrillators into 97 of these individuals. The thin battery-operated devices are implanted near the collarbone to monitor heart rate. When they detect an irregular heartbeat or arrhythmia, they send out an electrical shock to restore a healthy heartbeat.

A study published by the research team in the Journal of American College of Cardiology last year showed men given the defibrillators were still alive after five years, compared with only 72% in a control group.

Many of the defibrillators have fired several times, bringing the men back from death’s door. “They’re the walking dead,” says Ms. Young, who shares an irreverent sense of humour with many of her research subjects.

Mr. Winter will never forget the first time his defibrillator fired six years ago. He was in the woods with his chainsaw 130 kilometres from his home in Gander.

Mr. Winter had just felled a tree when all of a sudden he got a “head spin.”

He fell forward but then the “defib” shocked him back to life.

Mr. Winter counted his blessings and was soon back at work. Two years later the “defib” fired again. Twelve months later it went off again.

“There was one day it was a little too close,” he says.

On doctors’ advice, Mr. Winter quit logging in 2004 and also gave up volunteering for the fire department. He is now a stay-at-home dad, while his wife works full-time. The disease has also cut into his fishing and hunting because he must forfeit his driver’s licence for months whenever the defibrillator fires.

He admits it can be hard, like the day last fall when he had to tell his boys he couldn’t go “rabbit catching” because his heart was acting up.

Two weeks later he underwent a 10-hour operation that burned away the fibrous growths in his heart.

The surgery was so successful, Mr. Winter’s defibrillator has not fired in months. He has just reclaimed his licence and is busy burning gas in his truck.

Mr. Winter, a willing “guinea pig,” says he would do almost anything to help the researchers better understand the disease and find a cure.

The challenges are not not just scientific, they are also ethical and social.

The Memorial team can determine with 95% accuracy who carries the gene for ARVC, which is believed to have struck down one boy at 17.

To be on the safe side, the medical team now likes to run heart tests on 10-year-old boys.

“Then we start talking about when to do the DNA tests,” says Ms. Hodgkinson, who says boys as young as 11 have been told they carry the gene and will get defibrillators. Testing in girls is not being pushed because ARVC has not struck a woman younger than 37.

The Winters pray their sons, Travis, 7, and Phillip, 5, are free of the gene. “It’s OK if they inherited everything else except Corey’s heart problems,” says Christine.

“To be honest with you, I wish it was 20,” Mr. Winter says of the recommendations that tests start at age 10. “One of the worst parts of knowing so much about the gene disorder is that children must now deal with it so young.”

Ms. Winter is philosophical, saying, “It’s better to know and do something about it, otherwise you live in fear.”


Most families affected by inherited ARVC willingly sign over their blood for DNA testing and embrace the use of defibrillators.

But some people who donated blood before anyone realized how deadly the ARVC gene was have refused to hear their test results.

One young man refused contact with the research team and died from ARVC before his 30th birthday, geneticist Kathy Hodgkinson and ethicist Daryl Pullman report in a recent paper in Clinical Genetics that highlights some of the “moral distress” created by the quest for the ARVC gene.

In another case, the researchers feared for public safety when a gene carrier started training for a job in transportation.

Ms. Hodgkinson won’t say if he wanted to fly a plane or drive a train. But she says many people might have died if he had collapsed on the job.

The young man eventually agreed to change career paths and got treatment.

One woman refuses to acknowledge she has the gene and passed it on to her now-grown children. When her blood was collected for gene analysis the consent form gave her the option to decide whether or not to learn the DNA results, says Ms. Hodgkinson. The woman declined and wants no contact with the researchers.

Ms. Hodgkinson and Mr. Pullman say the children, who are now adults, should decide for themselves if they want to be tested and offered defibrillators that could save their lives. They argue the researchers have a moral, if not a legal, responsibility to act in such cases, even if it means breaching patient privacy.

The researchers have sent the woman a letter “strongly, strongly advising her to share information about the disease with her children,” Ms. Hodgkinson said in an interview.

They have also written to her doctor, breaching confidentiality in the hope the physician will be able to alert family members.

“Just imagine,” Ms. Hodgkinson says, if one of them drives a school bus and collapses at the wheel. “It would be horror of horrors if the school bus driver and all the kids are killed.”

Ms. Hodgkinson says the team continues to grapple with how to deal with such troubling cases. One solution might be to handle serious but treatable genetic conditions such as ARVC like infectious diseases. Health authorities could be notified and warn relatives, much like they alert people exposed to HIV or tuberculosis.

“The difference with infectious disease is you can infect anyone,” says Ms. Hodgkinson. “Here you are talking about saving the lives, potentially, of the people to whom you are related.”

• Black & White Photo: Scott Cook, for CanWest News Service / Newfoundlander Corey Winter, with his sons Travis and Phillip (right), has inherited a deadly genetic illness.


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