Discovery behind ‘hole in the heart’ impacting half of population living with Down syndrome

Posted 3 weeks ago by David McManus
Understanding symptoms and early detection could save the life of someone with Down syndrome. [Source: Shutterstock]
Understanding symptoms and early detection could save the life of someone with Down syndrome. [Source: Shutterstock]

About 1 in every 1,100 babies born in Australia will have Down syndrome, half of which will have a heart condition.

Key points:

  • Down syndrome affects approximately one in 800 new births and is caused by an extra third copy of chromosome 21
  • About 50 percent of infants with Down syndrome have some form of heart condition, compared with approximately one percent of typical infants
  • Atrioventricular septal defect is the most frequently diagnosed congenital heart condition in children with Down syndrome, with an incidence rate between 30 and 47 percent of congenital heart defects in children with Down syndrome


A recent discovery, published in Science Translational Medicine, has set the scene for potential future therapies for heart conditions in people with Down syndrome.

Researchers at the Francis Crick Institute and University College London have identified a gene that causes heart defects called ‘Dyrk1a’ on human chromosome 21 using genetic mapping on human Down syndrome fetal hearts, as well as embryonic hearts from a mouse model of Down syndrome.

This gene has previously been linked to cognitive impairment and facial changes in Down syndrome, but its role in heart development was not known.

An extra copy of Dyrk1a turned down the activity of genes required for cell division in the developing heart and the function of the mitochondria, which produce energy for the cells.

These changes correlated with a failure to correctly separate the chambers of the heart.

The team found that while Dyrk1a is required in three copies to cause heart defects in mice, it was not sufficient alone.

As a result of this discovery, another unknown gene must also be involved in the origin of heart defects in Down syndrome and the team is looking into uncovering the mysterious gene.

Researchers were able to reduce the overactivity of the Dyrk1a gene and partially reversed these heart defects in mice through testing a DYRK1A inhibitor on mice which were pregnant with pups that model the heart defects in people with Down syndrome.

Victor Tybulewicz, group leader of the Immune Cell Biology Laboratory & Down Syndrome Laboratory, explained that the human heart forms early in the womb and it may not be possible to screen for these conditions and potentially reverse a defect.

“Our research shows that inhibiting DYRK1A can partially reverse changes in mouse hearts, suggesting that this may be a useful therapeutic approach,” he said.

“However, in humans the heart forms in the first eight weeks of pregnancy, likely before a baby could be screened for Down syndrome, so this would be too early for treatment.

“The hope is that a DYRK1A inhibitor could have an effect on the heart later in pregnancy or even better after birth. These are possibilities we are currently investigating.”

Eva Lana-Elola, principal laboratory research scientist at the Francis Crick Institute and co-first author, said: “It was remarkable that just restoring the copy number of one gene from 3 to 2 reversed the heart defects in the mouse model for Down syndrome.”


“We’re now aiming to understand which of the other genes on this extra chromosome are involved. Even though Dyrk1a isn’t the only gene involved, it’s clearly a major player in many different aspects of Down syndrome.”


The researchers worked with Perha Pharmaceuticals to test the DYRK1A inhibitor. The company is now testing the drug in a clinical trial for cognitive disorders associated with Down syndrome and Alzheimer’s disease.

People with Down syndrome are living longer and healthier lives than they have in the past, according to Down Syndrome Australia.

The life expectancy of people with Down syndrome has dramatically increased over the past 50 years, with the average life expectancy of a person with Down syndrome in Australia being 60 years of age.


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