Genetic testing detects heart failure risk in children

Researchers at the Centenary Institute and the Murdoch Children’s Research Institute (MCRI) have shown that genetic testing for cardiomyopathy in children and their first-degree relatives (a parent or sibling) provides a precise clinical diagnosis that could guide treatment options. Their findings, published in the journal Circulation: Genomic and Precision Medicine, evaluated the genetic causes of infant and childhood-onset cardiomyopathy.

A disease that involves a weakened heart muscle, cardiomyopathy makes it hard for the heart to pump blood effectively around the body. Children with cardiomyopathy are more likely than adults to develop life-threatening arrhythmias and severe heart failure, and to require heart transplantation. While rare in infants and children, cardiomyopathy often results in significant health problems and death.

“Genetic testing allows us to look for variations (mutations) in the genes known to cause cardiomyopathy,” said Dr Richard Bagnall, Head of the Centenary Institute’s Bioinformatics and Molecular Genetics Laboratory and lead author of the new study. He said that in addition to wanting to understand the genetic basis for the disease, the research team wished to find out why some infants and children end up with heart failure and need a transplant, while their parents and siblings do not.

In the study, 221 children (aged 18 years and under) with cardiomyopathy were recruited from paediatric cardiology services or genetic heart diseases clinics in Melbourne and Sydney. Where possible, family members were also genetically tested. About a third of the participants developed cardiomyopathy at less than a year old and about a third received a heart transplant.

In their analysis, the researchers were able to attribute known gene mutations to 50% of the childhood cardiomyopathy cases investigated. According to Bagnall, “We established that cardiomyopathy in children often has an underlying and known genetic basis.

“When a child required a transplant but family members didn’t, we often found that the gene mutation causing the disease was not found in their parents or that the child had two separate variants — one from each parent.”

The research also uncovered variants in genes that cause multi-organ syndromic diseases, which have not been clinically diagnosed before because the characteristic features are not fully developed yet in children.

MCRI Professor Robert Weintraub said understanding the cause of these serious and sometimes life-changing conditions was important for patients and their families.

“Knowing that a gene mutation is a cause of their child’s condition can provide answers to otherwise unresolved questions,” he said. “In addition to the scientific knowledge gained about which mutations cause heart muscle conditions at different ages, unaffected children from the same family, who do not have the gene change, no longer require ongoing surveillance.

“Children who have the mutation may not develop the condition but do require close follow-up. There is still a lot to learn however, particularly in those families where no gene mutation has been found.”

Bagnall said the findings demonstrate that the genetic diagnosis of childhood cardiomyopathy has important clinical benefits, leading to more precise and quicker diagnosis and identifying recessive and other gene variants.

“Genetic testing can often mean a more accurate diagnosis that can guide therapeutic approaches, inform prognosis and help in better identifying other family members who may also be at risk of developing the disease,” he said.

Image credit: iStock.com/didesign021

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