Hidden genetic culprit found for sudden cardiac deaths of young people

Families who have lost young people to sudden, unexplained cardiac deaths are being offered long-sought answers following a major genetic discovery by New Zealand and Australian researchers.

Scientists have identified a previously overlooked genetic abnormality that could cause sudden cardiac death in young people – a finding that promises to improve diagnosis, guide screening and help prevent future deaths.

Each year, up to 90 unexplained sudden cardiac deaths were reported in New Zealand among people under 40. In around a third of cases, no cause had previously been identified.

The breakthrough emerged after a New Zealand family and two Australian families – who had lost young relatives to sudden cardiac death – agreed to advanced genetic testing using cutting edge sequencing techniques. Earlier standard genetic tests had found no explanation.

"This new finding has been made possible by the technology we have available now," said lead researcher Dr Polona Le Quesne Stabej from the University of Auckland.

"In 2001, sequencing the entire human genome cost more than two billion dollars. Now it can be done for between one and three thousand dollars."

The New Zealand family had been supported for years by specialists from the national Cardiac Inherited Diseases Group, which was founded in 2000 to coordinate care for whānau affected by inherited heart conditions.

Professor Jon Skinner, who established the group, said the lack of answers had been distressing for both families and clinicians.

He said it was heartbreaking to be caring for the whānau and terrible to not understand what was going on.

"Parents who have lost a child often carry an irrational sense of guilt, and it has been a powerful motivator for me and the team when a parent says, 'Thank you doctor, I don't have to blame myself any more.'"

The discovery was made through a research project led by Pūtahi Manawa, the University of Auckland's centre of excellence for heart research.

In 2024, the New Zealand family agreed to take part in the project, which was later published in the European Heart Journal.

Researchers used long read DNA sequencing — an advanced method capable of analysing complex regions of the genome that standard tests often miss.

By applying this technique to historical DNA samples, the team identified a genetic abnormality known as a "repeat expansion" within the DMPK gene.

Bioinformatician Dr Zoe Ward analysed the whole genome data and made the key discovery. Repeat expansions were challenging to detect with conventional testing and had gone unnoticed in earlier investigations.

The abnormality is known to cause myotonic dystrophy type 1, an inherited condition associated with muscle weakness and other symptoms. In some cases, it can also disrupt the heart's electrical system.

"Our findings suggest this genetic change may be an overlooked cause of sudden cardiac death in young people, especially when standard tests find no answer," Le Quesne said.

"We recommend checking for this DMPK repeat in unexplained cases."

The New Zealand findings were confirmed in Australia by Associate Professor Richard Bagnall from the Centenary Institute, a leading expert in inherited heart disease. Bagnall identified the same genetic expansions in several Australian cases of sudden cardiac death.

Together, the researchers said the evidence strongly supported including the DMPK gene in routine genetic screening for unexplained cardiac deaths.

A Māori advisory group, known as the Kaitiaki Rōpu, played a central role in steering the New Zealand research and ensuring it was culturally safe. The family at the centre of the study was Māori.

The rōpu oversaw consent processes, decisions about DNA use and disposal, and the inclusion of tikanga such as karakia throughout the research.

"DNA is one of the most taonga substances — everything about us, about our whakapapa, is in our DNA," said rōpu member Saraya Hogan (Ngāti Hako), a genetic counsellor and medical laboratory scientist involved in the project.