Key result
Clinical genetic testing and exome sequencing identified a definitive molecular cause in 48% of previously tested and 21% of previously untested children with cardiomyopathy.
Why the study?
Practice variations exist despite guideline recommendations for genetic testing in pediatric cardiomyopathy, and robust data on clinical testing practices and diagnostic yield in children are lacking.
Observational (n=152)
Yes
Exome sequencing can identify a definitive molecular genetic diagnosis in a substantial proportion of children with cardiomyopathy, supporting the routine use of genetic testing in this population.
Answers are grounded in this paper and cite their sources.
Adds diagnostic yield data for genetic testing in pediatric cardiomyopathy; leaves open effects on management and outcomes.
Background Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing ( P =0.005 and P =0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes. Conclusions A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first‐degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01873963.
No takes yet. Share an insight, caveat, or question.
Ware et al. (2021) conducted an observational in Pediatric cardiomyopathy (n=152). Genetic testing and exome sequencing was evaluated on Identification of a molecular cause (positive genetic test result). Clinical genetic testing and exome sequencing identified a definitive molecular cause in 48% of previously tested and 21% of previously untested children with cardiomyopathy.
Synapse has enriched 10 related papers. Consider them for comparative context: