先天性长QT综合征的研究进展

先天性长QT综合征(LQTS)是心肌细胞膜离子通道功能异常导致心肌细胞复极时间延长的心脏传导异常疾病.心电图特征为QT间期延长和尖端扭转性室性心动过速.临床表现为反复发生心源性昏厥,甚至猝死.目前分子遗传学研究已经发现与LQTS相关的至少12个突变基因,分别定位于3、4、7、11、12、17、20和21号染色体上,控制...     

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??Long QT syndrome??LQTS?? is the first found genetic ion channel disease. LQTS patients can show various clinical types?? from a lifetime of being asymptomatic to infantile sudden death?? which can cause malignant ventricular arrhythmia?? syncope?? epileptic seizures?? cardiac arrest and sudden cardiac death. The genetics of LQTS pathogenesis is currently considered specific genetic mutations that can lead to abnormal procedure of depolarization and repolarization of cardiac muscle cell. At the molecular level?? the pathogenesis of LQTS is the 15 different susceptible gene mutations of alpha and beta subunit that encoded ion channels. KCNQ1??KCNH2 and SCN5A mutations account for more than 90% of all mutations in patients with LQTS??and the remained 12 mutations account for only less than 10%. Precision medicine for LQTS mainly lies in the application of beta receptor blockers. Currently it’s believed that beta receptor blockers is better in the treatment of LQTS1 than in LQTS2 and LQTS3. Patients with LQT3 have low beta adrenergic receptor density?? and attacks are mainly related to rest and slow heart rate. Sodium channel blockers are more often recommended in clinical treatment??such as mexiletine??fluorine carney??etc.     

Coexistence of congenital long QT syndrome and autonomic dysregulation in children

Loss of consciousness (LOC) in long QT syndrome (LQTS) patients can be caused by torsade de pointes (TdP) or vasovagal syncope (VVS). On genetic testing and head‐up tilt testing (HUTT), we diagnosed three young patients with both genotyped LQTS and autonomic dysregulation. According to grade of prolongation of QT interval and LOC status, syncope episodes in two patients were classified as due to VVS, while those of the other patient were due to TdP. We also diagnosed one patient with postural orthostatic tachycardia syndrome. Syncope in LQTS patients should not automatically be labeled TdP. If there is a possibility of VVS, HUTT should be performed, but careful observation is required because TdP cannot be completely ruled out.     

Successful uses of magnesium sulfate for torsades de pointes in children with long QT syndrome

BACKGROUND: Administration of magnesium sulfate (MgSO4) is an effective and safe treatment for torsades de pointes (TdP) associated with acquired long QT syndrome (LQTS) in adults. As for children, there are few reports focusing on it. The authors discuss the efficacy of MgSO4 for TdP in children with congenital and acquired LQTS. The authors also discuss the optimal administration dosage and serum magnesium (SMg) concentration during MgSO4 therapy. METHODS: The authors studied seven consecutive LQTS children undergoing MgSO4 therapy for TdP. Of the seven children, five were congenital LQTS and two were acquired LQTS. A bolus injection of MgSO4 was given intravenously over 1-2 min followed by continuous infusion for the next 2-7 days. RESULTS: Of the seven patients, six responded completely to the initial bolus. The bolus dosage was 5.9 +/- 3.8 mg/kg (range, 2.3-12 mg/kg) in these six, and the other remaining one (neonate with congenital LQTS) required a total of 30 mg/kg until complete abolishment. The continuous infusion was given at rates of 0.3-1.0 mg/kg per h and patients did not show recurrence of TdP. The SMg concentration was 3.9 +/- 1.0 mg/dL (2.9-5.4 mg/dL) immediately after bolus injection. The mean corrected QT (QTc) interval before and after bolus injection did not show significant difference. CONCLUSION: Intravenous infusion of MgSO4 was effective for TdP in children with LQTS, and MgSO4 abolished TdP without shortening the QTc interval. The optimal bolus dosage, infusion rates and SMg concentration were 3-12 mg/kg, 0.5-1.0 mg/kg per h and 3-5 mg/dL, respectively.     

遗传性长QT间期综合征KCNQ1基因的新突变

目的　研究遗传性长QT间期综合征 (longQTsyndrome ,LQTS)的临床特点并筛查KCNQ1基因突变。方法　首先按照国际公认的诊断标准 ,确立先证者 ,进行家系调查 ,共有 6个LQTS家系被纳入研究。另选 50名心电图正常且校正QT间期 (QTc)≤ 0 41s的健康人作为正常基因对照。分析先证者及家系成员的临床和心电图资料 ,采用聚合酶链反应 单链构像多态性 (polymerasechainreaction singlestrandconformationalpolymorphism ,PCR SSCP)方法 ,对KCNQ1基因编码区全部序列进行基因突变筛查。阳性结果行DNA测序以明确具体突变位点 ,并进行对照研究。结果　 6个家系中共有LQTS患儿 13例 ,男 5例 ,女 8例。其中 ,猝死 1例 ( 8% ) ;晕厥发作 10例 ( 77% ) ;无症状 2例 ( 15% ) ,分别在家系调查和基因筛查时被发现。共采集到 11例患儿的心电图 ,QT间期为 ( 0 460± 0 0 58)s ,QTc为 ( 0 516± 0 0 58)s。经基因检测发现KCNQ1基因上 2个新的致病性突变位点 3 56 3 57ΔQQ和 62 6 63 1ΔGSGGPP ,分别来自 2个家系。还发现 1个新的多态性位点P448R。此 3个位点均位于编码蛋白C 末端结构域。结论　该研究发现KCNQ1基因的 2个新缺失突变位点和 1个新的多态性位点 ,系国内外首次报道 ,丰富了LQTS离子通道突变的基因库资料     

Clinical and electrophysiological features of Japanese pediatric long QT syndrome patients with KCNQ1 mutations

Background: The purpose of the present paper was to determine the clinical and electrophysiological features of Japanese pediatric long QT syndrome (LQTS) patients with KCNQ1 mutations (LQT1). Methods: KCNQ1 mutations were analyzed in 13 Japanese pediatric patients with prolonged QT interval on electrocardiogram (ECG). These LQT1 patients were reviewed, retrospectively, for the presence of past and family histories of LQTS‐related cardiac events, other complications, and their ECG findings evaluated at rest and during exercise). Results: KCNQ1 mutations were identified in eight patients (61.5%) from six unrelated families. Four missense mutations were identified in seven patients and an insertion/deletion in one. The mutations were located in the transmembrane domain in four patients and the C‐terminal domain in four. Syncope did not occur in patients with the C‐terminal domain mutations up to the age of 6–9 years, but family members of patients with the C‐terminal domain mutations had a history of syncope in their elementary school days. Compared with a non‐LQTS control group, peak heart rate (HR) on exercise and the HR increase during exercise were significantly lower in the LQT1 group (LQT1 vs control, 155 ± 16 beats/min vs 182 ± 13 beats/min, P < 0.01, 66 ± 16 beats/min vs 99 ± 24 beats/min, P < 0.01, respectively). Conclusions: The risk of LQTS‐related cardiac events may not be different in pediatric LQT1 patients with C‐terminal domain mutations than in patients with transmembrane domain mutations. Possible sinus node dysfunction or a poor HR response to sympathetic stimulation has been suggested in pediatric LQT1 patients.     

Circadian rhythm of the autonomic nervous system in long QT syndrome

The circadian changes in the activity of the autonomic nervous system in a group showing long QT duration in electrocardiogram (ECG) were studied in order to differentiate symptomatic congenital long QT syndrome from asymptomatic. The asymptomatic group presented only long QT duration (QTc > 0.46). Seven girls and two boys, including two subjects experiencing syncope of non-neurological origins, were examined by using heart rate (HR) power spectrum analysis. In three subjects, the peak of the high frequency band, indicating the parasympathetic activity, disappeared during night-time (sleep), which means the possibility of a high risk of sudden cardiac death. In two of three subjects, moreover, the averaged sympathetic activity during daytime was significantly increased compared to that during night-time, in addition to the abrupt increase of sympathetic activity in the morning. These two subjects, in which one boy had a family history of Romano-Ward syndrome, were the same people experiencing the syncope attack. We succeeded in objectively elucidating that congenital long QT syndrome is adrenergic-dependent, and suggest that HR power spectrum analysis may be of value in distinguishing symptomatic congenital long QT syndrome from asymptomatic showing only long QT duration.     

Reproducibility of corrected QT interval in pediatric genotyped long QT syndrome

Reproducibility of corrected QT interval (QTc), especially QTc after exercise, has not been thoroughly investigated. We reviewed charts of pediatric patients who underwent treadmill‐exercise stress testing without medication multiple times within 1 year. In patients with long‐QT syndrome (LQTS; n = 22), the discrepancy in QTc between two treadmill exercise stress tests using Fridericia's formula was 14 ± 12 ms at rest, 13 ± 12 ms 4 min after exercise, with a maximum of 14 ± 12 ms after exercise. There was no statistically significant difference in QTc between the two tests. Intraclass correlation coefficients (ICC) were 0.84, 0.85, and 0.85, respectively. In controls (n = 13), the discrepancy in QTc was 18 ± 12 ms at rest, 14 ± 7 ms 4 min after exercise, with a maximum of 14 ± 9 ms after exercise. There was no significant difference in QTc between the two tests. ICC were 0.78, 0.80, and 0.80, respectively. QTc calculated using Bazett's formula also showed high reproducibility. Reproducibility of QTc in children is high at rest and after exercise.     

Macroscopic T wave alternans in long QT syndrome

A 6 year old girl was admitted with recurrent episodes of loss of consciousness. ECG showed prolonged QT interval and macroscopic T Wave alternans. Identification of this ECG pattern is important since it can lead to potentially lethal arrhythmias.     

Sick sinus syndrome with seroconstrictive pericarditis in malignant lymphoma involving the heart: A case report

A case of the sick sinus syndrome and constrictive pericarditis with effusion (seroconstrictive pericarditis) as manifestations of lymphomatous involvement of the heart is presented. Autopsy findings documented infiltration of the sinus node by undifferentiated malignant lymphoma cells. The clinical course is described and problems with diagnosis and management of such a complication are discussed. This is one of the few cases in the literature in which an uncommon cause of conduction system disease and pericardial constriction was substantiated by electrocardiogram, angiography, and autopsy.     

Hypocalcaemia mimicking long QT syndrome: case report

We describe a teenage girl who presented with syncope on exertion and prolonged QT on electrocardiogram (ECG). She was found to be hypocalcaemic due to hypoparathyroidism. Following oral calcium and vitamin D supplementation, there were no further episodes of syncope with normalization of the QT segment. This case highlights the need to consider all causes of a long QT segment.     

儿童长QT综合征及其尖端扭转型室性心动过速的预防、管理与紧急处理

长QT综合征(Long QT interval syndrome,LQTS)是以心电图上QT间期延长和室性心律失常为特征的一种离子通道病.该病的发生与钾通道蛋白、钠通道蛋白、钙通道相关因子和膜适配蛋白的基因突变密切相关,现已证实了13种导致LQTS的突变基因.其临床特征主要表现为心电图QT间期异常延长、巨幅T波交替等,以及因此发生的尖端扭转型室性心动过速(Torsades de Pointes)、晕厥甚至猝死.心律失常事件的发生和基因型密切相关.LQTS1通常在运动和情绪激动时发生心律失常,而LQTS2则在安静时或突然出现声音时发生.儿童LQTS合并尖端扭转型室性心动过速发作时可导致循环灌注迅速恶化,具有生命危险,需要紧急处理.尖端扭转型室性心动过速发作的紧急处理包括静推硫酸镁、直流电击转复心律失常、纠正电解质等内环境紊乱、去除导致QT延长的药物.LQTS治疗的长效管理包括生活方式干预、口服β受体阻滞剂、植入心律转复除颤仪、左心交感神经切除以及靶向药物等.     

Familial symptomatic sinus bradycardia: Autosomal dominant inheritance

Symptomatic sinus bradycardia, due to either sick sinus syndrome or vagotonia, can be familial, affecting several members of a family. We report an 18-year-old male patient with palpitations and limited exercise capacity who was noted to have severe sinus bradycardia. His resting heart rate was 40/min, with normal PR and corrected QT intervals, and sinus pauses up to 6 seconds during sleep. Exercise treadmill test and pharmacologic autonomic blockade during electrophysiologic studies abolished the bradycardia, suggestive of vagotonia rather than intrinsic sinus node dysfunction. This patient's father and a female cousin had a similar clinical history but associated with syncope and severe sinus bradycardia. The mode of transmission appeared to be autosomal dominant. All three have permanent demand pacemakers implanted and are asymptomatic.     

先天性QT间期延长综合征相关基因SCN5A定点突变及蛋白表达研究

目的：构建先天性QT间期延长综合征相关基因SCN5A-delQKP1507 1509突变型真核表达载体,并观察其在人胚肾293（HEK293）细胞中的表达。方法：采用一步法构建SCN5A-delQKP1507-1509突变型真核表达载体PEGFP-delQKP-hH1,用脂质体转染法将野生型和突变型质粒分别转染HEK293细胞,激光共聚焦显微镜观察钠通道蛋白在HEK293细胞的表达与定位,Western blot检测其蛋白表达。结果经电泳及DNA测序显示突变型1507-1509位点成功缺失9个碱基,野生型与突变型均在HEK293细胞膜上表达,且表达量差异无统计学意义（P>0.05）。结论成功构建钠通道基因SCN5A-delQKP1507-1509突变型真核表达载体,并在HEK293细胞中表达,为进一步研究其功能奠定基础。     

Perinatal manifestations of idiopathic long QT syndrome

A neonate who had presented with sustained irregular heart rate during labor was found to have QT prolongation and repetitive polymorphic ventricular tachycardia (torsades de pointes) postnatally. Propranolol and propafenone successfully controlled the ventricular arrhythmias. Follow-up electrocardiograms and Holter records show persistent QT prolongation, bizarre T waves, and intermittent episodes of T wave alternans. On propranolol monotherapy the boy is thriving and completely free of ventricular arrhythmias. In the rare case of long QT syndrome in the neonate, early detection and therapy are mandatory to prevent ventricular arrhythmias and sudden death.     

新生儿获得性QT间期延长致功能性房室传导阻滞9例报告

目的探讨新生儿尤其是早产儿严重窒息缺氧复苏后缓慢性心律失常的发生机制及治疗原则。方法回顾性分析9例严重窒息患儿复苏后出现QT间期异常延长导致功能性2∶1房室传导阻滞（AVB）临床经过。结果9例患儿年龄（3.3&#177;1.6）h;胎龄（31.6&#177;3.0）周;出生时体重（1776.1&#177;646.3）g;入院诊断：产时重度窒息7例,吸入性肺炎2例。均于入院35h内出现进行性QT间期延长致功能性的2∶1AVB,QTc（791.6&#177;139.9）ms,且血清离子钙浓度从平均1.02mmol/L,降至0.32mmol/L。经肾上腺素、大剂量VitC、葡萄糖酸钙、果糖,并予纠正酸中毒及其他对症治疗。治愈3例,死亡6例。结论QT间期异常延长导致功能性的2∶1AVB是新生儿尤其是早产儿严重窒息缺氧后出现的一种缓慢性心律失常,预后不良。治疗关键在于预防。     

中国儿童短QT综合征首例报告及家系调查

目的探讨中国儿童短QT综合征的临床特征及遗传学特点。方法对中国医科大学附属第一医院儿科于2006年收治的1例儿童短QT综合征患儿(患儿男,13岁,以晕厥、抽搐1次为主诉入院,既往健康)临床资料进行分析,并对患儿父母两个家系的22名成员进行遗传学调查。结果查体无异常所见。体表心电图示窦性心律,Q-T间期240ms,QTc270ms,Ⅱ、ⅡI、avF、V4-6导联T波高尖;Holter心电图除见上述改变外,还可见房性和室性期前收缩,心脏彩色超声和心脏X线片未见异常;心肌酶谱、肌钙蛋白和血钾、钠、钙等离子检测值均在正常范围。家系调查表明患儿母亲于12年前猝死在家中,之前曾有反复晕厥、抽搐发作史。体表心电图示Q-T间期260～280ms,T波高尖。在多次住院抢救观察期间,心电图显示尖端扭转型室速、心室颤动。除患儿母亲外,其他成员均无晕厥、抽搐及猝死史,患儿父亲心电图Q-T间期380ms,其他健在者也未见Q-T间期缩短。结论短QT综合征可表现为晕厥、抽搐发作,心电图Q-T间期缩短、QTc≤300ms,心脏结构正常,可有家族猝死史。本例符合常染色体显性遗传。     

小儿严重脓毒症并发多器官功能障碍综合征的研究

目的 小儿脓毒症是PICU的常见疾病,具有较高的病死率.本研究旨在了解小儿脓毒症的临床特点及转归,探寻儿童严重脓毒症的死亡危险因素.方法 分析2008年1月至12月收入我院PICU的脓毒症病例,对严重脓毒症患儿作单因素分析,并建立Logistic回归模型,探寻儿童严重脓毒症的死亡危险因素.结果 纳入脓毒症患儿103例,病死率16.5%.严重脓毒症45例,其死亡危险因素是PRISM Ⅲ评分(OR 1.502;95%CI 1.131～1.995)和病程中外周血血小板计数最高值(OR 0.991;95%CI0.982～1.000).小儿严重脓毒症伴随1、2、3、4个及4个以上脏器功能障碍的病死率分别为10.0%、11.1%、44.4%、68.8%,差异具有非常显著性(P＜0.001).最常受累的是心血管系统(75.6%)和呼吸系统(66.7%),严重脓毒症伴发MODS死亡危险因素是呼吸系统(OR 23.179;95%CI2.095～256.522)和肾脏(OR 9.637;95%CI 1.698～54.703)功能受累.结论 小儿严重脓毒症的死亡危险因素是PRISM Ⅲ评分和病程中外周血血小板计数最高值.小儿脓毒症合并MODS提示预后不良,其病死率与发生功能障碍的脏器数目呈正相关,呼吸系统和肾脏功能受累是儿童脓毒症死亡的危险因素.