Skip to main content

The Globe and Mail

Newfoundland's sudden-death riddle resolved

For at least nine generations, a curse of sudden death has stalked Newfoundland families.

Men and women have dropped dead in the prime of their lives - eating supper on the sofa, cleaning the stove, teaching a math class.

For 12 years, researchers have hunted the culprit behind the scourge that can stop hearts without warning. But that search is over.

Story continues below advertisement

In a discovery that is already saving lives and soothing minds, researchers at Memorial University in St. John's have identified the precise genetic glitch responsible for centuries of heartbreak in the province.

"This has caused massive young deaths across the generations ... the stories have been recorded in the family Bibles," said Kathy Hodgkinson, co-author of the report published yesterday in the American Journal of Human Genetics.

Newfoundlanders aren't the only ones who suffer from Type 5 Arrhythmogenic Right Ventricular Cardiomyopathy, or ARVC. But the cluster of affected families, many of whom descend from the region's first few settlers, brought attention to the disorder after their plight was described in the New England Journal of Medicine in the 1980s. Still, ARVC is not well understood and estimates of its prevalence in the general population range from one in 1,000 people to one in 5,000.

"It's hard to diagnose ... you have to have a family history of people dropping dead," said co-author and molecular geneticist Terry-Lynn Young. "Some people believe it's vastly underdiagnosed."

In people who suffer ARVC, healthy heart cells are mysteriously replaced by fatty, fibrous tissue, particularly on the right ventricle. Eventually, the buildup results in an arrhythmia, or an irregular heartbeat, that can trigger the heart to beat more than 300 times a minute, quivering until it finally halts.

"The first symptom is often death," said Ms. Hodgkinson, the genetic counsellor who spent a dozen years tracking affected families and collecting their DNA.

In 1998, along with German collaborators, Memorial University researchers tracked the culprit to a region on chromosome 3. This allowed researchers to estimate who faced a high or low risk of the disorder, but it carried a 5-per-cent error rate. People at high risk were offered defibrillators. One hundred people chose to have them implanted under their skin to jolt their hearts in the event of sudden arrest.

Story continues below advertisement

But a gene test can now tell people with certainty if they are indeed at risk of sudden cardiac death.

Researchers found the gene in a study of 15 affected families with 257 members. More than half of those affected - or 144 people - carried the same mutation in a gene known as TMEM43. The mutation, Dr. Young said, involves a single chemical change in the code. The change was not seen in any control subjects or in the unaffected family members.

"That one change is enough to cause the replacement of healthy heart cells with fat and fibre," Dr. Young said.

Men who carry one copy of the mutated gene have a median life expectancy of 41 years, women of 71. Researchers suspect hormones may offer premenopausal women some protection from the heart condition.

This gene discovery, unlike most, has immediate applications. For Rosalie Cater, 56-year-old mother of three from Grand Falls-Windsor, Nfld., "it is the best news anyone can ever hope for."

She had grown up with the fear. She'd heard about her maternal grandfather who turned up for his shift at the mill on Boxing Day, pulled on one of his work boots and slumped over. He was 49. It killed her mother at 72. All three of her brothers were affected - Graham died at a Chinese restaurant at 26, Terry on the back porch at 43, and although Doug died of cancer, he passed it to his son, who collapsed in front of his math students at age 28.

Story continues below advertisement

"I always had that inkling that I had it ... but I thought women get it later," said Ms. Cater, who had a defibrillator implanted in 2002.

But it was her three sons she worried about most. Genetic testing has since confirmed that only her eldest son, Tim, 30, carries the gene mutation, and knowing has already saved his life twice. His defibrillator went off four times one night while he played hockey, she said, twice when he was snowmobiling.

Victoria Connolly, who lives outside St. John's, had always assumed that she, too, was a carrier. One brother died at 42, her sister died at 56, one nephew died at 39, another at 26.

"Oh I was convinced I had this," said Ms. Connolly, 54. "I'd wake up in the middle of the night in a sweat, my heart pounding out of my body, and I'd grab my husband - 'Paul, is this it? Is this it?' "

Ms. Connolly was afraid to go anywhere alone. She worried for her daughters too, "wondering which day it was going to be." Then, two weeks ago she heard the astonishing words from genetic counsellor Ms. Hodgkinson: "My dear, you are 100 per cent in the clear."

"It's hard to describe the relief," Ms. Connolly said. "I can go to bed now and sleep."

Report an error Licensing Options
Comments

The Globe invites you to share your views. Please stay on topic and be respectful to everyone. For more information on our commenting policies and how our community-based moderation works, please read our Community Guidelines and our Terms and Conditions.

We’ve made some technical updates to our commenting software. If you are experiencing any issues posting comments, simply log out and log back in.

Discussion loading… ✨

Combined Shape Created with Sketch.

Combined Shape Created with Sketch.

Thank you!

You are now subscribed to the newsletter at

You can unsubscribe from this newsletter or Globe promotions at any time by clicking the link at the bottom of the newsletter, or by emailing us at privacy@globeandmail.com.