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Diagnostic Yield of Exome Sequencing in Pediatric Cardiomyopathy
Julia Keisling1, Emma Bedoukian2, Danielle S Burstein3
1Rugters, The State University of New Jersey, New Brunswick, NJ.
Insights
Exome sequencing (ES) offers a high diagnostic yield for pediatric cardiomyopathy, identifying genetic causes missed by gene panels. This genetic testing approach is crucial for accurate diagnosis in children with heart conditions.
Area of Science:
- Genetics
- Pediatric Cardiology
- Genomic Medicine
Background:
- Pediatric cardiomyopathy often has a genetic basis, yet no definitive genetic testing is standard care.
- Current diagnostic approaches may not capture the full spectrum of genetic causes.
- Early and accurate genetic diagnosis is vital for effective management and family counseling.
Purpose of the Study:
- To evaluate the diagnostic utility of exome sequencing (ES) for diagnosing pediatric cardiomyopathy.
- To compare the diagnostic yield of ES against traditional gene panel testing in this population.
- To determine if diagnostic yield varies by age or cardiomyopathy subtype.
Main Methods:
- Retrospective chart review of 91 pediatric cardiomyopathy patients.
- Inclusion criteria: diagnosis of cardiomyopathy and evaluation by a medical geneticist (2010-2022).
- Data abstracted included demographics and clinical information.
Main Results:
- Exome sequencing yielded a diagnosis in 36.3% (39.6%) of pediatric cardiomyopathy patients.
- Over 61% of these diagnoses would have been missed by cardiac multigene panel testing.
- Diagnostic yield was similar for infants (<1 year: 38.3%) and older children (>1 year: 41.9%).
Conclusions:
- Exome sequencing demonstrates a significantly higher diagnostic yield compared to gene panels for pediatric cardiomyopathy.
- ES identifies a substantial number of genetic diagnoses not detectable by gene panels.
- The utility of ES is consistent across age groups and cardiomyopathy subtypes, supporting its use in all pediatric cases.
Objective:
To assess the diagnostic yield of exome sequencing (ES) in pediatric cardiomyopathy.
Study Design:
A single-institution, retrospective chart review of 91 patients with pediatric cardiomyopathy was performed. While pediatric cardiomyopathy is often genetic in nature, no genetic test is recommended as standard of care. All our patients were diagnosed with cardiomyopathy and evaluated by a medical geneticist between January 2010 through September 2022. Demographic information and clinical data were abstracted.
Results:
Of 91 patients with pediatric cardiomyopathy, 36 (39.6%) received a diagnosis by ES. Twenty-two (61.1%) of these diagnoses would have been missed on cardiac multigene panel testing. The diagnostic yield for cardiomyopathy presenting under 1 year of age was 38.3%, while the yield for patients over 1 year of age was 41.9%.
Conclusions:
ES has a high diagnostic yield in pediatric cardiomyopathy compared with a gene panel. Over 60% of patients with diagnosis by ES would not have received their molecular genetic diagnosis if only multigene panel testing was sent. Diagnostic yield did not vary significantly between the subtypes of cardiomyopathy and patient age groups, highlighting the likely clinical utility of ES for all pediatric cardiomyopathy patients.
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