Intellectual and Neurodevelopmental Delays in Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: Distinct Characteristics and a More Malignant Neurocardiac Phenotype.

IF 9.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation. Arrhythmia and electrophysiology Pub Date : 2025-09-26 DOI:10.1161/CIRCEP.124.013437

Christina Y Miyake, Dania Kallas, Sara B Stephens, Oliver M Moore, Xander H T Wehrens, Peter S Fischbach, Martin J LaPage, Andrew P Landstrom, Ian H Law, Allison C Hill, Prince J Kannankeril, Frank A Fish, Taylor S Howard, Santiago O Valdes, Tam Dam Pham, Jeffrey J Kim, Santokh Dhillon, Christopher L Johnsrude, Ulrich Krause, Georgia Sarquella-Brugada, Peter Kubus, Terezia Tavacova, Sit-Yee Kwok, Susan P Etheridge, Svjetlana Tisma-Dupanovic, Adam C Kean, Andrew D Krahn, Mohammed Ebrahim, Joseph Atallah, Anne Fournier, Anjan S Batra, Ming-Lon Young, James Perry, Joshua R Kovach, Anna N Kamp, Bradley C Clark, Erick Jimenez, Fatme Charafeddine, Robert M Hamilton, Seshadri Balaji, Shubhayan Sanatani

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引用次数: 0

Abstract

Background: Marked intellectual and neurodevelopmental delay (INDD) was noted in 6 unrelated patients diagnosed with RYR2-related catecholaminergic polymorphic ventricular tachycardia (CPVT) from a single center. Patients exhibited similar distinct phenotypic features not previously described. We aimed to determine the prevalence of INDD in CPVT, compare clinical characteristics between patients with CPVT with and without INDD, and investigate the possibility of a unique neurocardiac CPVT phenotype.

Methods: Retrospective combined review of patients with RYR2-related CPVT diagnosed ≤18 years with and without INDD from a single center and the International Pediatric CPVT Registry. Patients with hypoxic ischemic insult were excluded unless INDD preceded injury.

Results: Among a total of 168 patients, INDD was reported in 19 (11.3% [95% CI, 7.0%-17.1%]). When compared with cases without INDD, patients with INDD exhibited distinct features including (1) younger age at onset of symptoms (median 7.0 versus 10.0 years; P=0.04); (2) higher frequency of atrial tachyarrhythmias (84.2% versus 16.3%, P<0.001); (3) atrial or ventricular tachycardia without adrenergic stimulation (81.3% versus 2.2%, P<0.001, 31.6% versus 4.5%, P=0.001 respectively); (4) cardiac structural changes or systolic dysfunction (36.8% versus 1.3%, P<0.001); and (5) higher incidence of cardiac arrest or sudden death after diagnosis (26.3% versus 2.7%, P=0.001). INDD-related RYR2 genetic variants clustered within the central and channel domains and may be specific to certain variants.

Conclusions: This study demonstrates a wider spectrum of RYR2-related disease, with a subset associated with extracardiac manifestations. Certain RYR2 variants may lead to a neurocardiac phenotype with distinct features that are important to recognize, as these patients may be at higher risk.

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儿童儿茶酚胺能多形性室性心动过速的智力和神经发育迟缓：不同的特征和更恶性的神经心脏表型。

背景：在6例被诊断为ryr2相关儿茶酚胺能多态性室性心动过速（CPVT）的非相关患者中发现了显著的智力和神经发育迟缓（INDD）。患者表现出先前未描述的相似的独特表型特征。我们的目的是确定CPVT中INDD的患病率，比较伴有和不伴有INDD的CPVT患者的临床特征，并探讨一种独特的神经心脏CPVT表型的可能性。方法：回顾性联合分析来自单一中心和国际儿科CPVT登记处的诊断为ryr2相关CPVT的患者≤18岁，伴有或不伴有INDD。排除缺氧缺血性损伤患者，除非损伤前有INDD。结果：168例患者中，有19例（11.3% [95% CI, 7.0%-17.1%]）报告了INDD。与无多动症的患者相比，患有多动症的患者表现出明显的特征，包括：(1)发病年龄更小（中位年龄7.0岁对10.0岁，P=0.04）；(2)房性心动过速频率较高（84.2% vs . 16.3%， PPP=0.001）；(4)心脏结构改变或收缩功能障碍（36.8% vs 1.3%， PP=0.001）。与indd相关的RYR2遗传变异聚集在中心和通道结构域内，并且可能特定于某些变异。结论：这项研究表明ryr2相关疾病的范围更广，其中一个亚群与心外表现相关。某些RYR2变异可能导致具有明显特征的神经心脏表型，这一点很重要，因为这些患者可能面临更高的风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Circulation. Arrhythmia and electrophysiology 医学-心血管系统

CiteScore

13.70

自引率

4.80%

发文量

187

审稿时长

4-8 weeks

期刊介绍： Circulation: Arrhythmia and Electrophysiology is a journal dedicated to the study and application of clinical cardiac electrophysiology. It covers a wide range of topics including the diagnosis and treatment of cardiac arrhythmias, as well as research in this field. The journal accepts various types of studies, including observational research, clinical trials, epidemiological studies, and advancements in translational research.