Year: 2025
Type: review
Abstract: Cardiomyopathy in children is a leading cause of heart failure and cardiac transplantation. Disease-associated genetic variants play a significant role in the development of the different subtypes of disease. Genetic testing is increasingly being recognized as the standard of care for diagnosing this heterogeneous group of disorders, guiding management, providing prognostic information, and facilitating family-based risk stratification. The increase in clinical and research genetic testing within the field has led to new insights into this group of disorders. Mutations in genes encoding sarcomere, cytoskeletal, Z-disk, and sarcolemma proteins appear to play a major role in causing the overlapping clinical phenotypes called cardioskeletal myopathies through "final common pathway" links. For myocarditis, the high frequency of infectious exposures and wide spectrum of presentation suggest that genetic factors mediate the development and course of the disease, including genetic risk alleles, an association with cardiomyopathy, and undiagnosed arrhythmogenic cardiomyopathy. Finally, while we have made strides in elucidating the genetic architecture of pediatric cardiomyopathy, understanding the clinical implications of variants of uncertain significance remains a major issue. The need for continued genetic innovation in this field remains great, particularly as a basis to drive forward targeted precision medicine and gene therapy efforts. IMPACT: Cardiomyopathy and skeletal myopathy can occur in the same patient secondary to gene mutations that encode for sarcomeric or cytoskeletal proteins, which are expressed in both muscle groups, highlighting that there are common final pathways of disease. The heterogeneous presentation of myocarditis is likely secondary to a complex interaction of multiple environmental and genetic factors, suggesting a utility to genetic testing in pediatric patients with myocarditis, particularly those in higher risk groups. Given the high prevalence of variants of uncertain significance in genetic testing, better bioinformatic tools and pipelines are needed to resolve their clinical meaning.
Source: Pediatric Research
Institutions: Columbia University Irving Medical Center, Indiana University Indianapolis, Indiana University School of Medicine, Washington University in St. Louis, Cincinnati Children's Hospital Medical Center, University of Tennessee Health Science Center, Le Bonheur Children's Hospital, University at Buffalo, State University of New York
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Funders: Lance Armstrong Foundation, Armstrong Foundation, Pfizer, Children's Cardiomyopathy Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Pediatric Cardiomyopathy Registry, Training Program in Cardiovascular Signaling, Genetic Mechanisms of Anthracycline Cardiotoxicity in Pediatric Cancer Survivors, Atherosclerotic Risk and Response to Exercise Intervention in HIV+ Children, Cardiovascular Status of HAART-Exposed Infants/Children, Pediatric Cardiomyopathy Specimen Repository, Pediatric HIV/AIDS Cohort Study (PHACS) Coordinating Center (CC) (U01), Therapeutic Index of Acute Lymphoblastic Leukemia, HAART Associated Cardiotoxicity in HIV-Infected Children, Primary Cardiomyopathies in Children: Research Directions & Strategies, G5560106399, Women and Infants Transmission Study IV, Baseline Predictors of Outcomes of Pediatric Dilated Cardiomyopathy, Pediatric HIV/AIDS Cohort Study (PHACS): Data and Operations Center (DOC)., FELLOWSHIP IN CLINICAL RESEARCH, G7947996496, G9000029296, G9000036457
OpenAlex ID: W4407269244