PDF(Pubmed)
Abstract：
UNASSIGNED: Monoallelic and biallelic TTN truncating variants (TTNtv) may be responsible for a wide spectrum of musculoskeletal and cardiac disorders with different age at onset. Although the prevalence of heterozygous TTNtv is relatively high in the general population, cardiac phenotyping (mainly cardiomyopathies, CMPs) in biallelic titinopathy has rarely been described in children.
UNASSIGNED: We reviewed the medical records of pediatric patients with biallelic TTNtv and cardiac involvement. Clinical exome sequencing excluded pathogenic/likely pathogenic variants in major CMP genes.
UNASSIGNED: Five pediatric patients (four male) with biallelic TTNtv were included. Major arthrogryposis multiplex was observed in four patients; no patient showed intellectual disability. At a cardiac level, congenital heart defects (atrial and ventricular septal defects, n = 3) and left ventricular non-compaction (n = 1) were reported. All patients had dilated cardiomyopathy (DCM) diagnosed at birth in one patient and at the age of 10, 13, 14, and 17 years in the other four patients. Heart rhythm monitoring showed tachyarrhythmias (premature ventricular contractions, n = 2; non-sustained ventricular tachycardia, n = 2) and nocturnal first-degree atrio-ventricular block (n = 2). Cardiac magnetic resonance (CMR) imaging was performed in all patients and revealed a peculiar late gadolinium enhancement distribution in three patients. HyperCKemia was present in two patients and end-stage heart failure in four. End-organ damage requiring heart transplantation (HT) was indicated in two patients, who were operated on successfully.
UNASSIGNED: Biallelic TTNtv should be considered when evaluating children with severe and early-onset DCM, particularly if skeletal and muscular abnormalities are present, e.g., arthrogryposis multiplex and congenital progressive myopathy. End-stage heart failure is common and may require HT.
UNASSIGNED: We reviewed the medical records of pediatric patients with biallelic TTNtv and cardiac involvement. Clinical exome sequencing excluded pathogenic/likely pathogenic variants in major CMP genes.
UNASSIGNED: Five pediatric patients (four male) with biallelic TTNtv were included. Major arthrogryposis multiplex was observed in four patients; no patient showed intellectual disability. At a cardiac level, congenital heart defects (atrial and ventricular septal defects, n = 3) and left ventricular non-compaction (n = 1) were reported. All patients had dilated cardiomyopathy (DCM) diagnosed at birth in one patient and at the age of 10, 13, 14, and 17 years in the other four patients. Heart rhythm monitoring showed tachyarrhythmias (premature ventricular contractions, n = 2; non-sustained ventricular tachycardia, n = 2) and nocturnal first-degree atrio-ventricular block (n = 2). Cardiac magnetic resonance (CMR) imaging was performed in all patients and revealed a peculiar late gadolinium enhancement distribution in three patients. HyperCKemia was present in two patients and end-stage heart failure in four. End-organ damage requiring heart transplantation (HT) was indicated in two patients, who were operated on successfully.
UNASSIGNED: Biallelic TTNtv should be considered when evaluating children with severe and early-onset DCM, particularly if skeletal and muscular abnormalities are present, e.g., arthrogryposis multiplex and congenital progressive myopathy. End-stage heart failure is common and may require HT.
摘要：
■单等位基因和双等位基因TTN截短变体（TTNtv）可能与不同年龄的肌肉骨骼和心脏疾病有关。尽管杂合子TTNtv在普通人群中的患病率相对较高，心脏表型（主要是心肌病，在儿童中很少描述双等位基因性肌动蛋白病的CMP）。
■我们回顾了双等位基因TTNtv和心脏受累的儿科患者的医疗记录。临床外显子组测序排除了主要CMP基因中的致病性/可能的致病性变异。
■包括5名患有双等位基因TTNtv的儿科患者（4名男性）。在4例患者中观察到严重的多发性关节炎；没有患者表现出智力障碍。在心脏水平，先天性心脏缺陷（心房和室间隔缺损，n=3）和左心室致密化（n=1）。所有患者均在一名患者出生时诊断为扩张型心肌病（DCM），其他四名患者在10、13、14和17岁时诊断为扩张型心肌病。心律监测显示快速性心律失常（室性早搏，n=2；非持续性室性心动过速，n=2）和夜间一级房室传导阻滞（n=2）。在所有患者中进行了心脏磁共振（CMR）成像，并在三名患者中发现了特殊的晚钆增强分布。两名患者存在高CK血症，四名患者存在终末期心力衰竭。需要心脏移植（HT）的终末器官损伤在两名患者中显示，手术成功的人。
■在评估患有严重和早发性DCM的儿童时，应考虑双等位基因TTNtv，特别是如果存在骨骼和肌肉异常，例如，多发性关节炎和先天性进行性肌病。终末期心力衰竭很常见，可能需要HT。
■我们回顾了双等位基因TTNtv和心脏受累的儿科患者的医疗记录。临床外显子组测序排除了主要CMP基因中的致病性/可能的致病性变异。
■包括5名患有双等位基因TTNtv的儿科患者（4名男性）。在4例患者中观察到严重的多发性关节炎；没有患者表现出智力障碍。在心脏水平，先天性心脏缺陷（心房和室间隔缺损，n=3）和左心室致密化（n=1）。所有患者均在一名患者出生时诊断为扩张型心肌病（DCM），其他四名患者在10、13、14和17岁时诊断为扩张型心肌病。心律监测显示快速性心律失常（室性早搏，n=2；非持续性室性心动过速，n=2）和夜间一级房室传导阻滞（n=2）。在所有患者中进行了心脏磁共振（CMR）成像，并在三名患者中发现了特殊的晚钆增强分布。两名患者存在高CK血症，四名患者存在终末期心力衰竭。需要心脏移植（HT）的终末器官损伤在两名患者中显示，手术成功的人。
■在评估患有严重和早发性DCM的儿童时，应考虑双等位基因TTNtv，特别是如果存在骨骼和肌肉异常，例如，多发性关节炎和先天性进行性肌病。终末期心力衰竭很常见，可能需要HT。
