Research Highlights

Sifting through the genetics of congenital heart defects

Published online 5 August 2016

Distinct genetic evidence explains why congenital heart defects have low occurrence among siblings. 

A new study has found that congenital heart defects (CHD) in children, when part of a syndrome involving other defects, are more likely to develop due to de novo mutations that aren’t inherited from the parents. 

An international team examined the coding portion of the genome, known as the exome, in 1,891 children with CHD. A large portion of these children (1,281) had isolated CHD, known as nonsyndromic CHD (NS-CHD). Another 610 children had CHD as part of a syndrome of other defects, known as syndromic CHD (S-CHD). The exomes of the parents of 1,365 of the children were also examined1.

The team found that S-CHD children tended to have genetic mutations that developed de novo, while NS-CHD children had inherited mutations. They also found three S-CHD disorders caused by previously unidentified mutations in three genes.

“This discovery will change the way we design congenital heart defect genetic studies in the future,” says geneticist Saeed Al Turki from King Abdulaziz Medical City in Riyadh, Saudi Arabia. Genetic studies of children with CHD will benefit more if designed to include the parents in syndromic cases, he explains, and to involve comparisons with children without the defects in non-syndromic cases. 

“The results of our work, together with others, will improve the quality of genetic counselling for children with congenital heart defects and will help guide family planning,” says Al Turki.

Congenital heart defects affect approximately one in every 100 newborn children.


  1. Sifrim, A. et al. Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. Nat. Genet. (2016).