Genetic issues in pediatric cardiomyopathy: Future research directions Wendy Chung a, ⁎, Jeffrey Towbin b a Columbia University, United States b Cincinnati Children's Hospital Medical Center, United States abstract article info Keywords: Pediatric cardiomyopathy Cardiac disease Genetics Genetic testing Pediatric cardiomyopathies are extremely heterogeneous in etiology and are thus associated with variability in prognosis and response to therapy. With increasing availability of clinical diagnostic tools and research methods to molecularly characterize genetic forms of cardiomyopathy and identify viral pathogens in myocarditis, we have the opportunity to define pediatric cardiomyopathies by molecular subtype and characterize the natural history of each subtype. By understanding the natural histories of the subtypes of pediatric cardiomyopathies, we can develop biomarkers for early stages of diseases and disease progression, and lay the foundations necessary for future clinical trials for treatment and primary prevention. © 2011 Elsevier Ireland Ltd. All rights reserved. Pediatric cardiomyopathies are challenging because of the ex- treme heterogeneity and the rarity of the disease. Within both hypertrophic and dilated cardiomyopathies there are dozens of etiologies, some of which are associated with isolated cardiac disease and others in which there are systemic manifestations. As a result there is extensive heterogeneity in age of onset, disease progression, response to therapy and outcome. These issues, in addition to the relatively limited number of children affected, result in difficulty in determining predictive approaches to prevention or improvements in outcome. 1. Goal: define the cause for all cases of cardiomyopathy in children We are entering a new era of molecular medicine in pediatric cardiomyopathy. With increasing availability of molecular diagnostic tools we can more readily diagnose myocarditis and many of the genetic causes of cardiomyopathies. By dissecting this heterogeneous group of disorders into subsets including those caused by mutations in genes encoding sarcomere, cytoskeletal, and desmosome proteins, cardioskeletalmyopathies including dystrophinopathies, inborn er- rors of metabolism, and genetic syndromes including Noonan syndrome, we are beginning to refine the clinical phenotypes and identify patterns within these subsets that were not discernible when the entire group of cardiomyopathies are lumped under one category. A high priority is being placed upon the identification of the full spectrum of genes and mutations associated with childhood forms of cardiomyopathy. This understanding of the pathogenesis of these cardiomyopathies is likely to help improve early diagnosis in family members and improved therapy and outcome prognostication. Ongoing research studies will benefit from the molecular character- ization and phenotype stratification of these disorders and should facilitate the development of better natural history data and ultimately identify effective therapies for subsets of patients with cardiomyopathy. As many patients are now having molecular genetic testing as part of clinical care, there is an unprecedented opportunity for researchers, patients, providers (cardiologists, geneticists, and medical examiners), and clinical diagnostic laboratories to work together to ensure that these data are entered into existing registries such as the Pediatric Cardiomyopathy Registry (PCMR) and expanding the scope of the registry to allow more children to be registered. The registry should include not only rich, standardized clinical and family history data, but also biospecimens including plasma, DNA, cell lines, and cardiac tissue when possible, as has been developed and funded at the Pediatric Cardiomyopathy Specimen Repository (PCSR).The cell lines will be of increasing importance as the technology for making cardiac-induced pluripotential stem cells (iPS cells) is now available and could potentially allow for the study of genetic complexity of individual patients in vitro. The clinical data and biospecimens should be made readily accessible to the research community of qualified investigators to facilitate well designed research studies and reduce the barrier of data and biospecimen collection for researchers. Recruitment of patients with rare diagnoses is increasingly possible through social media, online networks, and patient advocacy groups such as the Children's Cardiomyopathy Foundation and Hypertrophic Cardiomyopathy Association, and others. These newer relationships and approaches should be utilized to populate these registries in addition to the more traditional epidemiologic and physician referral approaches. A large well populated registry with molecular etiologies would allow for efficient planning and rapid recruitment for new studies of cardiomyopathies with specific well defined genetic etiologies. In children, despite comprehensive clinical evaluation including genetic testing, there are a large number of children who never have Progress in Pediatric Cardiology 32 (2011) 3–4 ⁎ Corresponding author at: Columbia University, 1150 St. Nicholas Avenue, Room 620, New York, NY 10032. Tel.: +1 212 851 5313; fax: +1 212 851 5306. E-mail address: wkc15@columbia.edu (W. Chung). 1058-9813/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ppedcard.2011.06.001 Contents lists available at ScienceDirect Progress in Pediatric Cardiology journal homepage: www.elsevier.com/locate/ppedcard