Clinical features and follow-up of congenital long QT syndrome in children with syncope as the first presentation / 中国小儿急救医学

Objective:To investigate the pathogenic genes, clinical features and treatment as well as follow-up of children with congenital long QT syndrome (LQTS).Methods:The clinical data, genetic test results and follow-up data of 16 congenital LQTS children with syncope as the first manifestation admitted to the Department of Cardiology, Beijing Children′s Hospital Affiliated to Capital Medical University from August 2016 to March 2023 were collected and retrospectively analyzed.Results:Among the 16 LQTS patients, the age of first syncope onset was 1.3-13.3 (7.37±3.41) years, and the interval between first syncope onset and clinical diagnosis was 0-48 (14.8±16.2) months.A total of 13 (81.3%) patients had triggers of syncope, of which nine were exercise-induced and four were emotional induced.Genetic testing was performed in 13 patients with LQTS, of which 12 (92.3%) were found to have pathogenic or suspected pathogenic mutations from KCNQ1, KCNH2, and SCN5A gene.The corrected QT interval of 16 patients was (550.0±50.2) ms, all cases≥460 ms.Schwartz scored 6.0 (5.0, 6.0) points, all cases≥4 points.All patients were initially treated with metoprolol or propranolol, of which 14 patients were followed up to date, three patients had recurrent syncope, and five patients stopped taking the medicines by themselves.One patient with high-dose metoprolol (LQT2) was treated with mexiletine after recurrent episodes.One patient who was intolerant to high-dose propranolol underwent left cardiac sympathectomy and was followed up after surgery without syncope episodes.None of the patients underwent implantable cardioverter defibrillator implantation. Conclusion:Children with LQTS and syncope symptoms have high positive rate of genetic tests.The genetic results could assist typing of patients with LQTS and guide treatment.Routine electrocardiogram screening in children with syncope may diagnose LQTS earlier and reduce misdiagnosis and missed diagnosis.β-blockers are the cornerstone of treatment for patients with LQTS.Strengthening follow-up management and improving patients′ treatment compliance is conducive to further improving the treatment response rate of patients.

Mutation spectrum and clinical features of congenital long QT syndrome in 20 children: a single center study / 中华实用儿科临床杂志

Objective:To explore the pathogenic genes, clinical characteristics and treatment follow-up of children with congenital long QT syndrome (LQTS).Methods:Clinical data of 20 cases diagnosed with congenital LQTS and underwent gene testing from April 15, 2011 to April 15, 2021 in Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University were retrospectively collected and analyzed using independent sample t-test and Fisher′ s exact probability method. Results:LQTS-related gene mutations were detected in all the 20 cases, and pathogenic or suspected pathogenic mutations were identified in 18 cases (90.0%). Five LQTS mutation genes were discovered, including KCNQ1, KCNH2, SCN5A, CACNA1C and AKAP9.Eighteen cases (90.0%) had positive symptoms, and 13 cases (65.0%) had definite inducements.The inducement of symptoms in children with LQTS type 1(LQT1) was related to exercise, the causes of syncope in LQT1 and Jervell-Lange-Nielsen syndrome type 1 (JLNS1) with complex heterozygous mutations were exercise or emotional agitation; the causes of syncope in LQTS type 2 (LQT2) were unrelated to exercise; severe exercise in LQTS type 3 (LQT3) resulted in symptoms; and seizure in LQTS type 8 (LQT8) was non-induced.The corrected QT(QTc) interval of 20 cases was (553.1±66.6) ms, with a range of 460-707 ms, among which 17 cases showed QTc≥480 ms.The electrocardiogram(ECG) manifestations of children with various types of LQTS were different.There was no significant difference in QTc between different genders, or between children with syncope and those without syncope (all P>0.05). The follow-up time was (3.4±2.3) years, ranging from 0 to 8.3 years.Seventeen children received treatment[beta blockers and implantable cardiovertor-defibrillator(ICD)] and 3 cases did not.By the end of the follow-up, 1 child died, 19 cases survived, and 2 cases of the surviving children lost consciousness. Conclusions:There is a high consistency between genetic diagnosis and clinical diagnosis of congenital LQTS.The positive rate of gene detection is 90.0%.The clinical manifestations and ECG characteristics vary with genotypes.Beta blockers are protective.ICD therapy can prevent sudden cardiac death when oral medication does not respond.

G604S-HERG mutation in LQT2 leads to autophagy via the UPR-related pathway

Congenital long QT syndrome (LQTS) is a heart channel disease associated with fatal ventricular arrhythmiasor cardiac arrest. Human ether-a-go-go-related gene (HERG) mutation is one of the main causes in type 2LQTS since it may lead to abundant immature HERG channel protein accumulate in the endoplasmic reticulum(ER). In our study, we have successfully constructed the G604S-HERG mutation in HEK293 cells anddemonstrated that the immature HERG protein on ER via Western blot and immunofluorescence. Herein wefound that unfolded protein reaction (UPR) process has been activated in order to counter this endoplasmicreticulum stress (ERS) since the main sensors got upregulated. Meanwhile, autophagy was also observed inthis process and verified by Western blot and transmission electron microscopy. To explore the relationshipunderlying autophagy and UPR in the condition of ERS, we found that PERK-EIF2a-CHOP axis was activated. Our findings provides insight for G604S-HERG mutation in type 2 LQTS.

Torsión de puntas en una paciente con síndrome de QT largo congénito durante el puerperio: Presentación de un caso / Torsades de pointes in a patient with congenital long QT syndrome during the puerperium: Case report

RESUMEN El síndrome de QT largo congénito es una enfermedad eléctrica primaria del corazón que predispone a la ocurrencia de arritmias ventriculares malignas. Se traduce en una prolongación del intervalo QT en el electrocardiograma y la torsión de puntas es la arritmia que ocasiona síncope y, en ocasiones, muerte súbita. El embarazo y el puerperio aumentan la incidencia de estos eventos. Se presenta el caso de una puérpera afectada que presentó crisis de ansiedad y desmayos interpretados como psicógenos. Se documentó torsión de puntas sin respuesta a los fármacos antiarrítmicos diponibles y se trasladó al centro de referencia (Instituto de Cardiología y Cirugía Cardiovascular), donde se aumentó la frecuencia de estimulación del marcapasos y, posteriormente, se implantó un desfibrilador automático. Se trata de un caso infrecuente que constituyó un verdadero reto en el tratamiento integral y emergente, todo lo cual posibilitó la supervivencia de la paciente.

ABSTRACT Congenital long QT syndrome is a primary electrical disorder of the heart which predisposes to the occurrence of malignant ventricular arrhythmias. It is characterized by a prolongation of the QT interval on the electrocardiogram and the torsade de pointes is the main associated arrhythmia, resulting in syncope and sudden cardiac death. Pregnancy and puerperium increase the incidence of those events. We present the case of a patient who suffered from this disorder, and during the post-delivery period, she had events of faint and anxiety interpreted as psychogenic. Torsades de pointes without response to the available antiarrhythmic drugs was documented and she was transferred to the reference center (Instituto de Cardiología y Cirugía Cardiovascular), where the pacemaker stimulation frequency was increased and, subsequently, an implantable cardioverter defibrillator was implanted. This is an infrequent case that was a real challenge for the comprehensive and emergent treatment, all of which enabled the survival of the patient.

Placement of an implantable cardioverter-defibrillator in an infant with congenital long QT syndrome: Anesthetic considerations.

Sudden cardiac arrest (SCA) in children is a rare, but catastrophic event. Children with cardiac pathology at particular risk include those with congenital long QT syndrome (CLQTS) and hypertrophic cardiomyopathy. CLQTS is a genetic disorder of the cardiac ion channels and is associated with significant risk of malignant ventricular arrhythmias and SCA. For symptomatic, untreated patients, the mortality rate is approximately 20% for the first year and 50% at ten years. Use of an implantable cardioverter-defibrillator (ICD) is recommended for the prevention of SCA in this patient population. We report a case of CLQTS, who after successful resuscitation from SCA, underwent ICD placement at our center.

Research progress of congenital long QT syndrome / 国际儿科学杂志

Congenital long QT syndrome ( LQTS) is a cardiac ion channel dysfunction, leading to prolonged myocardial repolarization time. It is characterized by the typical ECG QT interval prolongation and torsades de pointes. It shows clinical recurrence of cardiogenic syncope and even lead to sudden death. Molecular genetic studies have revealed a total of 12 forms of congenital LQTS caused by mutations in genes of the potassium, sodium and calcium channels or membrane adapter located on chromosomes 3, 4, 7, 11, 12, 17, 20 and 21. This review summarized the studies of the pathogenesis of LQTS and gene-related treatments.

Jervell and Lange-Nielsen Syndrome: Novel Compound Heterozygous Mutations in the KCNQ1 in a Korean Family

The Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive syndrome characterized by congenital deafness and cardiac phenotype (QT prolongation, ventricular arrhythmias, and sudden death). JLNS has been shown to occur due to homozygous mutation in KCNQ1 or KCNE1. There have been a few clinical case reports on JLNS in Korea; however, these were not confirmed by a genetic study. We identified compound heterozygous mutations in KCNQ1 in a 5-yr-old child with JLNS, who visited the hospital due to recurrent syncope and seizures and had congenital sensorineural deafness. His electrocardiogram revealed a markedly prolonged corrected QT interval with T wave alternans. The sequence analysis of the proband revealed the presence of novel compound heterozygous deletion/splicing error mutations (c.828-830 delCTC, p.S277del/c.921G>A, p.V307V). Each mutation in KCNQ1 was identified on the maternal and paternal side. With beta-blocker therapy the patient has remained symptom-free for three and a half years.

Cardiac Arrest under Anesthesia in a Child with Previously Undiagnosed Long QT Syndrome: A case report / 대한마취과학회지

Congenital long QT syndrome is a rare but potentially lethal disease, characterized by a corrected QT interval of at least 440 msec, ventricular arrhythmia, recurrent syncope, and sudden death. We experienced a case of sudden cardiac arrest during general anesthesia in a child who was later documented to have congenital long QT syndrome. We report this experience with a brief review of literature.

The mode and clinical implications of onset of spontaneous tosade de pointes in the congenital long QT syndrome / 中国介入心脏病学杂志

Objective To study the mode and clinical implications of onset of spontaneous tosade de pointes in the congenital long QT syndrome. Methods We reviewed electrocardiograms (ECGs) of 55 patients with congenital QT syndrome for syncope. Documentation of the onset of tosade de pointes was available for 16 patients. All these patients had "definitive long QT syndrome" by accepted clinical and ECG criteria. Results One hundren and forty-nine runs of tosade de pointes were documented in 16 patients,of whom,there were 130 runs of pause-dependent tosade de pointes. Conclusion Our results show that the pause-dependent tosade de pointes,which has been recognized as a hallmark of tosade de pointes in the acquired long QT syndrome,plays a major role in the genesis of tosade de pointes in the congenital long QT syndrome.

Clinical characteristics of congenital long QT syndrome families / 西安交通大学学报(医学版)

Objective To elucidate the clinical manifestati on s and electrocardiogram characteristics of congenital long QT syndrome families and try to find out the genotype of the long QT syndrome(LQTS) patients. Methods The routine clinical check up and ECG recordings we re done for the 3 family members. Both QT interval and QTc were measured. Diagno stic criteria for LQTS were defined by Schwartz. Results Fifteen family members were identified as with LQTS and 11 members with intermediate probability to LQTS. The clinical manifestatio ns and ECG characteristics were different from each other. Conclusion The clinical manifestations and ECG characterist ics of LQTS patients from family 1,family 2 and family 3 correspond with LQT2, L QT1 and LQT3, which is caused by HERG,KVLQT1 and SCN5A gene mutation.

A Case of Congenital Long QT Syndrome with Reccurent Syncope

Congenital long QT syndrome (LQTS) is a disease characterized by prolongation of ventricle repolarization and by the occurrence, usually during emotional or physical stress, of life-threatening arrhythmias that lead to sudden death in most symptomatic and untreated patients. Two variants have been initially identified:the original Jervell and Lange-Nielsen syndrome of congenital deafness and autosomal recessive inheritance, and the more frequent Romano-Ward syndrome of autosomal dominant inheritance. Evidence also shows that approximately 25 to 30% of the cases are sporadic with syncope and a prolonged QT interval but without showing evidence for familial involvement. Familial and sporadic cases have been grouped under the definition of congenital long QT syndrome. We experienced a case of congenital long QT syndrome in a 13-year-old female girl. She had episodes of recurrent syncope and QT interval prolongation(QTc=0.46sec) in electrocardiogram(ECG). The ECG of her mother showed QT interval prologation(QTc=0.46sec). After applying atenolol, the QT interval returned to normal range and syncope has not occurred. We report a case of congenital long QT syndrome with a brief review of related literatures.

A Case of Congenital Long QT Syndrome Associated with Deafness and Syncope

Congenital long QT syndrome (LQTS) is an inherited disease characterized by prolonged QT intervals and polymorphic ventricular tachycardia. The clinical manifestations vary from sudden cardiac death by ventricular arrhythmia to asymptom throughout life. In 1957, Jervell and Lange-Nielsen reported a syndrome of congen-ital sensory deafness associated with a prolonged QT interval in four children. The affected children had multiple syncopal episodes, and three died suddenly. The mode of inheritance is autosomal recessive. Affected persons are susceptible to recurrent syncope, and they have a high incidence of sudden death and short life expectancy. We report a case and review the literature on long QT syndrome diagnosed in a 30-year-old female with a history of convulsion and loss of consciousness during delivery.