Muhammad Tariq, Stephanie M Ware Muhammad Tariq, Stephanie M Ware, Department of Pediat- rics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, United States Author contributions: Tariq M and Ware SM wrote and ap- proved the manuscript. Supported by The Children’s Cardiomyopathy Foundation; Cin- cinnati Children’s Hospital’s Clinical and Translational Science Award, No. NIH-ULlRR026314 (Ware SM); and AHA Postdoc- toral Fellowship Award, No. 12POST10370002 (Tariq M) Correspondence to: Stephanie M Ware, MD, PhD, Depart- ment of Pediatrics and Herman B Wells Center for Pediatric Re- search, Indiana University School of Medicine, 1044 W. Walnut Street Indianapolis, IN 46202, United States. stware@iu.edu Telephone: +1-317-2748938 Fax: +1-317-2748679 Received: May 29, 2014 Revised: July 29, 2014 Accepted: September 4, 2014 Published online: November 26, 2014 Abstract Pediatric cardiomyopathies are clinically heterogeneous heart muscle disorders that are responsible for sig- nificant morbidity and mortality. Phenotypes include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, left ventricular noncompac- tion and arrhythmogenic right ventricular cardiomyopa- thy. There is substantial evidence for a genetic contri- bution to pediatric cardiomyopathy. To date, more than 100 genes have been implicated in cardiomyopathy, but comprehensive genetic diagnosis has been prob- lematic because of the large number of genes, the pri- vate nature of mutations, and difficulties in interpreting novel rare variants. This review will focus on current knowledge on the genetic etiologies of pediatric cardio- myopathy and their diagnostic relevance in clinical set- tings. Recent developments in sequencing technologies are greatly impacting the pace of gene discovery and clinical diagnosis. Understanding the genetic basis for pediatric cardiomyopathy and establishing genotype- phenotype correlations may help delineate the molecu- lar and cellular events necessary to identify potential novel therapeutic targets for heart muscle dysfunction in children. © 2014 Baishideng Publishing Group Inc. All rights reserved. Key words: Pediatric; Mutation; Exome sequencing; Sarcomere Core tip: Pediatric cardiomyopathy is a clinically and genetically heterogeneous heart muscle disease with five major phenotypes: hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, left ventricular noncompaction cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. The genetic basis of these cardiomyopathies has been iden- tified using traditional linkage analysis and sequencing. Novel gene discovery has been increased using modern next generation sequencing technologies, however the exact mechanisms of disease development are not fully known. In this review we focus on the current genetic knowledge of cardiomyopathies and their importance in diagnostic settings. Tariq M, Ware SM. Importance of genetic evaluation and testing in pediatric cardiomyopathy. World J Cardiol 2014; 6(11): 1156-1165 Available from: URL: http://www.wjgnet.com/1949-8462/full/v6/ i11/1156.htm DOI: http://dx.doi.org/10.4330/wjc.v6.i11.1156 INTRODUCTION Cardiomyopathy is a clinically heterogeneous disease with a strong genetic component which affects heart muscle [1] . In the pediatric population, 40% of children progress to death or transplantation within 5 years of diagnosis [2-5] . The overall incidence of cardiomyopathy TOPIC HIGHLIGHT Submit a Manuscript: http://www.wjgnet.com/esps/ Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx DOI: 10.4330/wjc.v6.i11.1156 1156 November 26, 2014|Volume 6|Issue 11| WJC|www.wjgnet.com World Journal of Cardiology WJC World J Cardiol 2014 November 26; 6(11): 1156-1165 ISSN 1949-8462 (online) © 2014 Baishideng Publishing Group Inc. All rights reserved. Importance of genetic evaluation and testing in pediatric cardiomyopathy WJC 6 th Anniversary Special Issues (3): Cardiomyopathy