Genetic Causes of Cardiomyopathy in Children: First Results From the Pediatric Cardiomyopathy Genes Study.
Genetic Causes of Cardiomyopathy in Children: First Results From the Pediatric Cardiomyopathy Genes Study.
复制标题
儿童心肌病的遗传原因：小儿心肌病基因研究的第一个结果。
DOI：
10.1161/jaha.120.017731
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发表时间：
2021-05-04
影响因子：
5.4
通讯作者：
Pediatric Cardiomyopathy Registry Study Group
中科院分区：
文献类型：
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作者：
Ware SM;Wilkinson JD;Tariq M;Schubert JA;Sridhar A;Colan SD;Shi L;Canter CE;Hsu DT;Webber SA;Dodd DA;Everitt MD;Kantor PF;Addonizio LJ;Jefferies JL;Rossano JW;Pahl E;Rusconi P;Chung WK;Lee T;Towbin JA;Lal AK;Bhatnagar S;Aronow B;Dexheimer PJ;Martin LJ;Miller EM;Sleeper LA;Razoky H;Czachor J;Lipshultz SE;Pediatric Cardiomyopathy Registry Study Group
Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. Of the 152 enrolled probands, 41% had a family history of cardiomyopathy. Of 81 (53%) who had undergone clinical genetic testing for cardiomyopathy before enrollment, 39 (48%) had a positive result. Genetic testing rates varied from 0% to 97% between sites. A positive family history and hypertrophic cardiomyopathy subtype were associated with increased likelihood of genetic testing (P=0.005 and P=0.03, respectively). A molecular cause was identified in an additional 21% of the 63 children who did not undergo clinical testing, with positive results identified in both familial and idiopathic cases and across all phenotypic subtypes. A definitive molecular genetic diagnosis can be made in a substantial proportion of children for whom the cause and heritable nature of their cardiomyopathy was previously unknown. Practice variations in genetic testing are great and should be reduced. Improvements can be made in comprehensive cardiac screening and predictive genetic testing in first‐degree relatives. Overall, our results support use of routine genetic testing in cases of both familial and idiopathic cardiomyopathy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01873963.
