Rapid Genome Sequencing Shows Diagnostic Utility in Infants With Congenital Heart Defects

Congenital heart disease (CHD) is the most common birth defect and a leading cause of infant mortality. CHD often has a genetic cause, and recent studies demonstrate the utility of genetic testing. In clinical practice, genetic testing continues to evolve, and the incorporation of rapid genome sequencing (rGS) in CHD is a recent development that requires evaluation. Although smaller studies demonstrate the value of rGS, they also highlight the burden of results interpretation.

We analyzed genetic testing in CHD at 2 time points, in 2018 and from 2022 to 2023, across a change in clinical testing guidelines from chromosome microarray to rGS.

In an analysis of 421 hospitalized infants with CHD, genetic testing was performed in 77.7%, and the rate was consistent across time and in all patient subtypes analyzed. There was a significant shift in testing modalities, where in 2018, chromosome microarray was the most common test performed, with diagnostic results for CHD in 14.3%, whereas in 2022 to 2023, rGS was the most frequent test performed, with results diagnostic for CHD in 16.9%. In addition, rGS identified 44% more unique genetic diagnoses than chromosome microarray.

This is the most extensive study to highlight the value of rGS in patients with CHD. These findings have important implications for CHD patient management.