| BackgroundCongenital long QT syndrome(LQTS)refers to a group of syndromes in which the body surface electrocardiogram(ECG)shows prolonged QT interval,abnormal T wave,which are easy to produce ventricular arrhythmias,especially torsadesde points(TdP),resulting in syncope and sudden death.The Incidence is 1:2500[1].At present,a total of 18 subtypes caused by mutations of 16 genotypes have been found,by different inheritance patterns,which can be divided into autosomal dominant Romano-Ward syndrome(RWS)and autosomal recessive Jervell-Lange Nielsen syndrome(JLNS).The clinical manifestations,inducements and ECGs of different subtypes have their own characteristics.Genetic testing has become an important way of diagnosis and antidiastole.At present,there are few long-term follow-up studies on LQTS in children based on medical centers in the world.Therefore,we conducted a single-center follow-up study on congenital long QT syndrome in children.ObjectiveTo collect and follow up the clinical data of children with congenital LQTS and their families in our center in the past 10 years,in order to explore the pathogenic genes,clinical characteristics and treatment follow-up of children with LQTS.MethodA total of 19 children diagnosed with congenital long QT syndrome and undergoing genetic testing were selected as the research subjects,who were admitted to the pediatric cardiac department of Shandong Provincial Hospital on January 1,2011 and December 31,2020.Clinical data and genetic testing data during hospitalization were collected and followed up.During the follow-up,we aimed to find out the status quo and treatment response of the children,and the medical history and family incidence were repeatedly confirmed.Finally we summarize and analyze the collected data.Results1.Totally there were 9 males(47.4%)and 10 females(52.6%).The age of first symptom was 5.1±4.2 years,and the age of diagnosis was 6.7±4.4 years.Twelve cases(63.2%)had positive family history,7 cases had family history of syncope or sudden death,8 cases had family history of QTc(corrected QT)interval prolongation.LQTS related gene mutations were detected in each of the 19 cases,and pathogenic or suspected pathogenic mutations were identified in 17 cases(89.5%).Five LQTS mutant genes were detected,including KCNQ1,KCNH2,SCN5A,CACNA1C,and AKAP9,corresponding to six phenotypes,including 6 cases of LQT1(31.6%),5 cases of LQT2(26.3%),1 case of LQT3(5.3%),and 3 cases of LQT8(15.8%).3 cases of JLNS1(15.8%),1 case of unknown phenotype(5.3%).2.Sevevteen cases(89.5%)had positive symptoms,including syncope,pale complexion,dizziness and slow heartbeat.Among the symptomatic children,12(70.6%)had definite inducement.Three cases(75%)of LQT1 children had syncope during running or playing football,and one case(25%)had syncope during walking or emotional excitement.Children with LQT2 had syncope attacks when they having a cold,looking at a mobile phone,feeling hungry,awakening,sleeping,and taking a hot spring.One child with LQT3 developed dizziness and bradycardia after strenuous exercise.LQT8 had no predisposing factors.All JLNS1 children had syncope during exercise or emotional excitement.3.Nine cases(47.4%)had arrhythmias besides prolonged QTC interval(corrected QT interval),4 cases with sinus bradycardia(SB),4 with premature ventricular contractions(PVC),and 3 with an atrioventricular block(AVB).One case(5.3%)with syndactyly,1 case(5.3%)with hypoglycemia.There were 3(15.8%)with abnormal cardiac structures,including 1 case of left ventricular enlargement,1 case of ventricular septal defect(VSD),and 1 case of patent ductus arteriosus(PDA)and pulmonary stenosis(PS).In addition,2 cases(10.5%)were born prematurely.4.The average QTc of 19 cases was 551.8±68.2 ms.Among them,16(84.2%)had QTc≥480ms.Among the 3 patients with QTc<480ms.2 patients were LQT1 and 1 case had unknown phenotype.The average QTC of 6 children with LQT1 was(496.3±31.9)ms,with a range of 460-543ms,5 children with LQT2 had an average QTc of(582.0±20.5)ms,ranging from 550-600ms.One child with LQT3 had the longest QTC of 520ms.The mean QTc was(570.0±70.0)ms in 3 children with LQT8,ranging from 490-620ms.The mean QTc of 3 children with JLNS1 was(635.7±79.5)ms,with a range of 550-707ms.The maximum QTC of ECG was 460ms in 1 child with unknown phenotype.While ECGs of LQT1 children showed wide base,bi-directional or normal T waves,children with LQT2 showed a T-wave notch,bidirectional T-waves,or a low flat T wave.Children with LQT3 showed late T waves and bi-directional T waves.Children with LQT8 showed a T-wave height cusp,and the 3 JLNS1 children showed wide base and bi-directional T wave changes.The mean QTC of female children(580.7±64.9)ms was higher than that of male children(519.8±59.4)ms,with P value of 0.049,and the difference was statistically significant.The mean QTc of 13(68.4%)patients with syncope was(560.2±72.3)ms,and the mean QTc of 6(31.6%)patients without syncope was(533.8±60.3)ms,P value was 0.45,the difference was not statistically significant.5.The average Schwartz score of the 19 children was 4.9±1.2 points,and 16 participants(94.7%)scored≥3.5 points.6.The loss of follow-up rate in this study was 0,5 cases(26.3%)were followed up by telephone.The mean follow-up time was(2.9±2.0)years,ranging from 0 to 7 years.By the end of follow-up,1(5.3%)LQT8 child died,18(5.3%)LQT2 children survived,and 1(5.3%)LQT2 child lost consciousness.Of the 19 cases,17 cases received drug and/or ICD treatment,3 cases(17.6%)were significantly effective,10 cases(58.8%)were effective,and 4 cases(23.5%)were ineffective.There was no difference between the treatment group and the non-treatment group,and the P value was 1.A total of 12 patients insisted on oral drug therapy,including 10 patients with oral propranolol,1 patient with oral metoprolol,and 1 patient with oral methicillin.Among the 10 cases of oral propranolol,1 case showed remarkable effect,6 cases showed effective effect and 3 cases showed no effect.Through examination,the effective rate was significantly higher than that of the children whose dose was less than 1.5 mg/kg·d(P=0.008).Three patients were treated with ICD and received oralβ-blocker.During follow-up,2 patients had no syncope and no ICD discharge,and 1 patient had recurrent syncope with ICD discharge more than 20 times per year.Conclusions1.Eight new mutation sites suspected to be related to LQTS are discovered.2.Congenital long QT syndrome is a monogenic arrhythmia disease,and the positive rate of genetic testing is more than the previously reported 72%.Genetic diagnosis and clinical diagnosis were highly consistent.3.Some cases of LQTS have only ECG changes or syncope without typical ECG features.Genetic testing is helpful for early diagnosis.4.The symptoms,causes and ECG characteristics of congenital LQTS vary with different types,and the characteristics of each type are not completely the same as those reported in the past.5.The beta blockers can be protective.Sudden cardiac death(SCD)can be prevented by ICD treatment when oral medication doses are inadequate or treatment fails. |
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