# Evaluation of Exome and Genome Sequencing for Critically Ill Pediatric Cardiac Patients

## TL;DR

Exome and genome sequencing provided useful diagnoses for 45% of critically ill pediatric cardiac patients, outperforming traditional genetic tests.

## Contribution

This study evaluates the diagnostic efficacy of exome/genome sequencing in critically ill pediatric cardiac patients, showing its superiority over traditional methods.

## Key findings

- ES/GS diagnosed 44.9% of critically ill pediatric cardiac patients.
- 81.8% of these diagnoses were directly linked to cardiac phenotypes.
- CMA and gene panels would have missed 80.6% and 36% of diagnoses identified by ES/GS, respectively.

## Abstract

Genetic testing guidelines for children in cardiac intensive care units (CICUs) are lacking despite a high prevalence of genetic diseases among this population. Advances in next-generation sequencing (NGS) technologies, especially exome and genome sequencing (ES/GS), enable a more comprehensive genetic evaluation than more traditional testing modalities such as chromosomal microarray (CMA). While testing recommendations exist for cardiomyopathies, primary arrhythmias, and pulmonary hypertension (PH), broad application of NGS, especially ES/GS, across indications for admission to CICUs has not been recommended. We aimed to evaluate the diagnostic efficacy of ES/GS in critically ill pediatric patients with cardiac disease via a retrospective chart review of patients who underwent clinical ES/GS in a quaternary hospital’s pediatric CICU between January 2020 and August 2023. Forty-nine patients underwent ES/GS. Primary cardiac phenotypes included congenital heart disease, ventricular dysfunction, arrhythmia, and PH. Diagnostic results were found in 22 patients (44.9%) with 18/22 (81.8%) linked to cardiac phenotypes. Diagnostic yield was not different among primary cardiac phenotype groups but was higher in patients with ECA. CMA and gene panels would have failed to make a substantial proportion (80.6% and 36%, respectively) of diagnoses made by ES/GS. As NGS technologies and capabilities to interpret ES/GS data mature, diagnostic abilities in pediatric cardiac disease will continue to advance.