Rippert Alyssa L, Trackman Sarah, Burstein Danielle, Gaynor J William, Griffis Heather, Seymour Christine, Ahrens-Nicklas Rebecca
Division of Human Genetics, Children's Hospital of Philadelphia, Pennsylvania, USA.
Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Hum Mutat. 2023 Oct 27;2023:8892833. doi: 10.1155/2023/8892833. eCollection 2023.
Pediatric cardiomyopathy (CM) has significant childhood morbidity and mortality which is caused by both genetic and environmental factors. Previous research has focused on identifying genetic variants in pediatric CM for diagnostic purposes, but not for risk stratification. The current study was modeled after previous work which showed an association between CardioBoost-classified disease-causing variants and an increased risk for severe clinical outcomes in adults with CM to assess if the same association is true in pediatric CM. This was a retrospective, single-center cohort study that evaluated outcomes in pediatric CM patients who were evaluated by the Children's Hospital of Philadelphia (CHOP). CardioBoost (CB) scores were generated for these patients, and scores were categorized as ≤0.1, 0.1-0.9, and ≥0.9. Composite endpoint was freedom from a major adverse cardiac event (MACE). 104 patients were included in the final analysis. 32 (31%) had DCM, 45 (43%) had HCM, and 27 (26%) had other CM. There was no significant association between CB score and clinical outcome in pediatric CM patients. Overall, this study highlights the continued deficits in variant interpretation for pediatric CM. We recommend using caution when applying this tool to stratify clinical outcomes in the pediatric population.
小儿心肌病（CM）在儿童期具有显著的发病率和死亡率，其由遗传和环境因素共同导致。先前的研究主要集中于识别小儿CM中的基因变异以用于诊断目的，而非风险分层。当前的研究是基于先前的工作进行建模，先前的工作表明在成人心肌病患者中，经CardioBoost分类的致病基因变异与严重临床结局风险增加之间存在关联，本研究旨在评估在小儿CM中是否也存在同样的关联。这是一项回顾性、单中心队列研究，评估了由费城儿童医院（CHOP）评估的小儿CM患者的结局。为这些患者生成了CardioBoost（CB）评分，并将评分分为≤0.1、0.1 - 0.9和≥0.9。复合终点是无重大不良心脏事件（MACE）。最终分析纳入了104例患者。32例（31%）患有扩张型心肌病（DCM），45例（43%）患有肥厚型心肌病（HCM），27例（26%）患有其他类型的CM。在小儿CM患者中，CB评分与临床结局之间无显著关联。总体而言，本研究凸显了小儿CM变异解读方面仍然存在的不足。我们建议在将该工具应用于小儿人群的临床结局分层时要谨慎。
