Journal Article Ahead of print
PubMed: 41572441 DOI: 10.1002/ajmga.70065
Impact of Rapid Exome Sequencing on Pediatric Patients With Cardiomyopathy and Acute Heart Failure.
Am J Med Genet A
Authors: Tameemi Abdalla Moady, Tova Hershkovitz, Clair Habib, Ori Attias, Amir Hadash, Galit Tal, Asaad Khoury, Josef Ben-Ari, Danny Eytan, Tamar Paperna, Karin Weiss
Affiliations
- Genetics Institute Rambam Health Care Center, Haifa, Israel.
- The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
- Pediatric Intensive Care Unit, Rambam Health Care Campus, Haifa, Israel.
- Metabolic Clinic, Ruth Rappaport Children's Hospital, Rambam Health Care Center, Haifa, Israel.
- Department of Pediatric Cardiology and Congenital Heart Disease in Adults, Rambam Health Care Campus, Haifa, Israel.
Abstract
Few studies describe the impact of rapid exome sequencing (ES) on pediatric cardiomyopathy in urgent clinical settings. Here, we retrospectively report the impact of rapid singleton ES in pediatric patients presented with acute heart failure and isolated cardiomyopathy or myocarditis, between 2021 and 2023 at a single tertiary care center. A total of nine patients were included; age range: 5 days-11 years (median 42 days). Eight patients (88.8%) presented in the first year of life. The turnaround time for the ES results was 5-14 days (median 9 days). The diagnostic yield was 5/9 (55.5%), confirming primary cardiomyopathy. The majority had dominant disorders (ACTC1, MYBCP3, TNNI3, and NKX2-5), with two (22.2%) occurring de novo. One patient had a recessive condition (MYBPC3). In three patients (33.3%) who rapidly deteriorated during hospitalization, ES results had a major impact on immediate medical management. In most patients, the diagnosis led to the avoidance of further metabolic workup, cardiac magnetic imaging and vitamin treatment. In two families with no prior history of cardiomyopathy, at-risk relatives were advised to initiate cardiac surveillance. Overall the results show high clinical impact due to a shorter time to diagnosis, a high diagnostic yield, an improved therapeutic approach, in addition to the facilitation of genetic counseling for family planning and cascade testing of relatives at risk.
MeSH
Heart Failure, Heart, Myocarditis, Diagnosis, Exome, Therapeutics, Cardiomyopathies