Inherited Cardiac Arrhythmia Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
J Am Coll Cardiol. 2019 Jul 23;74(3):346-358. doi: 10.1016/j.jacc.2019.05.022.
Arrhythmogenic cardiomyopathy (ACM) is a variably penetrant disease increasingly identified in young patients.
This study sought to describe the diverse phenotype, genotype, and outcomes in pediatric and adolescent patients.
Records from 1999 to 2016 were reviewed for individuals age <21 years with a consistent personal or family history. Patients were categorized by right ventricular (RV), left dominant (LD), or biventricular subtypes using 2010 Task Force Criteria or proposed features of LD disease, encompassing electrocardiographic, structural, histological, and arrhythmic characteristics. Genetic variants classified as pathogenic and/or likely pathogenic by 2015 American College of Medical Genetics and Genomics criteria in recognized disease-associated genes were included.
Manifest disease was evident in 32 patients (age 15.1 ± 3.8 years), of whom 22 were probands, including 16 RV, 7 LD, and 9 biventricular ACM. Nondiagnostic features were seen in 5 of 15 family members. RV disease was associated with cardiac arrest and ventricular tachycardia (p = 0.02) and prevalence of PKP2 variants (p < 0.01), whereas biventricular disease was associated with a younger age of onset (p = 0.02). LD ACM was associated with variants in DSP and LMNA, and biventricular ACM with more a diverse etiology in desmosomal genes. Cardiac arrest was observed in 5 probands (age 15.3 ± 1.9 years) and ventricular tachycardia in 10 (age 16.6 ± 2.7 years), 6 probands, and 4 family members. Features suggestive of myocardial inflammation were seen in 6 patients, with ventricular tachycardia and/or cardiac arrest in 3 patients. Cardiac transplantation was performed in 10 patients. There were no deaths. In RV and biventricular disease, electrocardiographic preceded imaging features, whereas the reverse was seen in LD disease.
ACM in the young has highly varied phenotypic expression incorporating life-threatening arrhythmia, heart failure, and myocardial inflammation. Increased awareness of early onset, aggressive disease has important implications for patient management and familial screening.
致心律失常性右室心肌病（ACM）是一种逐渐在年轻患者中发现的具有不同外显率的疾病。
本研究旨在描述儿科和青少年患者的不同表型、基因型和结局。
回顾了 1999 年至 2016 年期间年龄<21 岁的个体的记录，这些个体具有一致的个人或家族史。根据 2010 年工作组标准或左室优势（LD）疾病的拟议特征，使用 2010 年工作组标准或拟议的 LD 疾病特征，将患者分为右心室（RV）、左优势（LD）或双心室亚型，包括心电图、结构、组织学和心律失常特征。包含在公认的疾病相关基因中的 2015 年美国医学遗传学和基因组学学院分类为致病性和/或可能致病性的遗传变异。
在 32 名患者（年龄 15.1 ± 3.8 岁）中出现了明显的疾病，其中 22 名是先证者，包括 16 名 RV、7 名 LD 和 9 名双心室 ACM。15 名家族成员中有 5 名出现非诊断特征。RV 疾病与心脏骤停和室性心动过速相关（p=0.02），PKP2 变异的发生率较高（p<0.01），而双心室疾病与发病年龄较小相关（p=0.02）。LD ACM 与 DSP 和 LMNA 基因的变异相关，双心室 ACM 与桥粒蛋白基因的更多病因相关。在 5 名先证者（年龄 15.3 ± 1.9 岁）中观察到心脏骤停，在 10 名先证者（年龄 16.6 ± 2.7 岁）、6 名先证者和 4 名家族成员中观察到室性心动过速。6 名患者出现提示心肌炎症的特征，3 名患者出现室性心动过速和/或心脏骤停。10 名患者接受了心脏移植。没有死亡。在 RV 和双心室疾病中，心电图先于影像学表现，而在 LD 疾病中则相反。
年轻人中的 ACM 具有高度不同的表型表达，包括危及生命的心律失常、心力衰竭和心肌炎症。对早期发病、侵袭性疾病的认识提高，对患者管理和家族筛查具有重要意义。
