Journal Article

Clinical utility of exome sequencing in infantile heart failure

Berger, Justin H., Yang, Sandra, Lin, Kimberly, Ritter, Alyssa, Santani, Avni, Krantz, Ian, Leonard, Jacqueline, Bedoukian, Emma, Juusola, Jane, Ahrens-Nicklas, Rebecca C., Medne, Livija, Copenheaver, Deborah, Gray, Christopher, Skraban, Cara, Izumi, Kosuke

2020

Overview

Pediatric cardiomyopathy is rare, has a broad differential diagnosis, results in high morbidity and mortality, and has suboptimal diagnostic yield using next-generation sequencing panels. Exome sequencing has reported diagnostic yields ranging from 30% to 57% for neonates in intensive care units. We aimed to characterize the clinical utility of exome sequencing in infantile heart failure. Infants diagnosed with acute heart failure prior to 1 year old over a period of 34 months at a large tertiary children’s hospital were recruited. Demographic and diagnostic information was obtained from medical records. Fifteen eligible patients were enrolled. Dilated cardiomyopathy was the predominant cardiac diagnosis, seen in 60% of patients. A molecular diagnosis was identified in 66.7% of patients (10/15). Of those diagnoses, 70% would not have been detected using multigene next-generation sequencing panels focused on cardiomyopathy or arrhythmia disease genes. Genetic testing changed medical decision-making in 53% of all cases and 80% of positive cases, and was especially beneficial when testing was expedited. Given the broad differential diagnosis and critical status of infants with heart failure, rapid exome sequencing provides timely diagnoses, changes medical management, and should be the first-tier molecular test.

• Publisher: Elsevier Inc,Nature Publishing Group US,Elsevier Limited
• Subject: Biomedical and Life Sciences / Biomedicine / Brief Communication / Cardiomyopathies - genetics / Cardiomyopathy / Cardiomyopathy, Dilated - genetics / clinical utility / Exome - genetics / exome sequencing / Families & family life / Female / Genes / Genetic Testing - ethics / Genetic Testing - trends / Genetics / Genomes / Genomics / Heart failure / Heart Failure - diagnosis / Heart Failure - genetics / High-Throughput Nucleotide Sequencing - methods / Hospitals / Human Genetics / Humans / Infant / Infant, Newborn / Intensive care / Laboratories / Laboratory Medicine / Male / Medical records / Metabolism / Mitochondrial DNA / Patients / pediatric / Pediatrics / Transplants & implants / Treatment Outcome / Whole Exome Sequencing - methods / Whole Exome Sequencing - trends