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

Area of Science:

• Medical Genetics
• Pediatric Cardiology
• Genomic Medicine

Background:

• Congenital heart disease (CHD) is a major cause of infant mortality with a frequent genetic basis.
• Genetic testing is crucial for diagnosing CHD, with rapid genome sequencing (rGS) emerging as a key advancement.
• Evaluating the impact of evolving genetic testing technologies like rGS in clinical practice is essential.

Purpose of the Study:

• To assess the evolving landscape of genetic testing for congenital heart disease (CHD).
• To compare the diagnostic yield of chromosome microarray versus rapid genome sequencing (rGS) in CHD patients.
• To evaluate the clinical utility of rGS in a large cohort of infants with CHD.

Main Methods:

• Analysis of genetic testing data from 421 infants with CHD at two distinct time points (2018 and 2022-2023).
• Comparison of testing modalities, focusing on the shift from chromosome microarray to rapid genome sequencing (rGS).
• Evaluation of diagnostic yield and identification of unique genetic diagnoses across different testing methods.

Main Results:

• Genetic testing was performed in 77.7% of infants with CHD, with consistent rates across time and patient subtypes.
• A significant shift towards rGS was observed, with rGS becoming the most frequent test by 2022-2023.
• Rapid genome sequencing (rGS) demonstrated a higher diagnostic yield for CHD (16.9%) compared to chromosome microarray (14.3%) and identified 44% more unique genetic diagnoses.

Conclusions:

• This study represents the most extensive evaluation of rapid genome sequencing (rGS) in congenital heart disease (CHD) patients to date.
• The findings underscore the significant value and increased diagnostic power of rGS in identifying genetic causes of CHD.
• The results have critical implications for optimizing patient management strategies and genetic counseling for infants diagnosed with CHD.