2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Yield of Different Genomic Testing Approaches in Infants with Congenital Heart Disease

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The study aimed to evaluate the diagnostic yield of different genomic testing approaches in infants with congenital heart disease (CHD). Data from 296 infants with CHD were analyzed, and the results showed that the diagnostic testing yields were 16% for targeted CHD exome panels, 18% for exome sequencing, 18% for all exome sequencing-based testing types, and 31% for genome sequencing. There was a significant increase in diagnostic yield between all exome-based testing and genome sequencing.<br /><br />The authors concluded that genetic testing protocols in infants with CHD need to be regularly updated to keep up with the changing landscape of available genomic testing options. In their population, genome sequencing had a 13% increased diagnostic yield compared to exome sequencing and all exome sequencing-based testing. Therefore, genome sequencing-based protocols were found to have a significantly improved diagnostic yield over exome sequencing-based protocols.<br /><br />The study also identified the Botto categories with the highest and lowest diagnostic yields. Complex lesions had a diagnostic yield of 28%, while heterotaxy had a yield of 29%. On the other hand, left ventricular outflow tract obstructions had a yield of 16%, and right ventricular outflow tract obstructions had a yield of 14%.<br /><br />In addition, genome sequencing revealed two diagnoses that would not have been detectable by exome sequencing, including a complex chromosomal rearrangement and a deep intronic variant.<br /><br />The study used three possible genomic tests: targeted CHD exome panels, exome sequencing, and genome sequencing. Data were collected for infants assessed for CHD at less than 31 days of age and evaluated according to the Botto criteria, which groups lesions based on embryologic mechanisms.<br /><br />Overall, the findings suggest that genome sequencing has a higher diagnostic yield compared to other genomic testing options in infants with CHD. Regular updating of genetic testing protocols is necessary to incorporate the advancements in genomic testing technologies and improve diagnostic capabilities for CHD.

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Presenting Author - Gabrielle C. Geddes, MD; Co-Author - Erin E. Conboy, MD, FACMG; Co-Author - Sara M. Fitzgerald-Butt, CGC; Co-Author - Benjamin M. Helm, MS, CGC; Co-Author - Evan-Jacob Garcia, MD; Co-Author - Laura Haneline, MD; Co-Author - Riad Lutfi, MD; Co-Author - Larry W. Markham, MD; Co-Author - Melinda Markham, MD; Co-Author - Kelly J. Schmit, MS, LCG; Co-Author - Kayleigh A. Swaggart, PhD, MS, CGC; Co-Author - Stephanie M. Ware, MD, PhD;

Meta Tag

Cardiac/circulatory disorders

Cardiovascular System

Congenital Anomaly

Exome sequencing

Genome sequencing

Co-Author Erin E. Conboy, MD, FACMG

Co-Author Sara M. Fitzgerald-Butt, CGC

Co-Author Benjamin M. Helm, MS, CGC

Co-Author Evan-Jacob Garcia, MD

Co-Author Laura Haneline, MD

Co-Author Riad Lutfi, MD

Co-Author Larry W. Markham, MD

Co-Author Melinda Markham, MD

Co-Author Kelly J. Schmit, MS, LCG

Co-Author Kayleigh A. Swaggart, PhD, MS, CGC

Co-Author Stephanie M. Ware, MD, PhD

Presenting Author Gabrielle C. Geddes, MD

Keywords

genomic testing

diagnostic yield

infants

congenital heart disease

CHD

targeted CHD exome panels

exome sequencing

genome sequencing

Botto categories

genetic testing protocols