In order to assess the clinical manifestations and electrocardiogram (ECG) characteristics of Chinese long QT syndrome (LQTS) patients and describe the phenotype-genotype correlation, the subjects from 5 congenital LQTS families underwent clinical detailed examination including resting body surface ECG. QT interval and transmural dispersion of repolarization (TDR) were manually measured. Five families were genotyped by linkage analysis (polymerase chain reacting-short tandem repeat, PCR-STR). The phenotype-genotype correlation was analyzed. Four families were LQT2, 1 family was LQT3. Twenty-eight gene carriers were (14 males and 14 females) identified from 5 families. The mean QTc and TDRc were 0.56 +/- 0.04 s (range 0.42 to 0.63) and 0.16 +/- 0.04 s (range 0.09 to 0.24) respectively. 35.7% (10/28) had normal to borderline QTc (< or = 0.460 s). There was significant difference in QTc and TDRc between the patients with symptomatic LQTS and those with asymptomatic LQTS, and there was significant difference in TDRc between the asymptomatic patients and normal people also. A history of cardiac events was present in 50% (14/28), including 9 with syncope, 2 with sudden death (SD) and occurred in the absence of beta-blocker. Three SDs occurred prior to the diagnosis of LQTS and had no ECG record. Two out of 5 SDs (40%) occurred as the first symptom. Typical LQT2 T wave pattern were found in 40% (6/15) of all affected members. The appearing-normal T wave was found in one LQT3 family. Low penetrance of QTc and symptoms resulted in diagnostic challenge. ECG patterns and repolarization parameters may be used to predict the genotype in most families. Genetic test is very important for identification of gene carriers.
Arrhythmia/etiology ; Arrhythmia/genetics ; Asian Continental Ancestry Group ; Electrocardiography ; Genotype ; Long QT Syndrome/complications ; Long QT Syndrome/congenital ; Long QT Syndrome/*genetics ; Pedigree ; *Phenotype

Long QT interval is an important finding that is often missed by electrocardiogram interpreters. Long QT syndrome (inherited and acquired) is a potentially lethal cardiac channelopathy that is frequently mistaken for epilepsy. We present a case of long QT syndrome with multiple cardiac arrests presenting as syncope and seizures. The long QTc interval was aggravated by hypomagnesaemia and drugs, including clarithromycin and levofloxacin. Multiple drugs can cause prolongation of the QT interval, and all physicians should bear this in mind when prescribing these drugs.
Adult ; Defibrillators, Implantable ; Electrocardiography ; Heart Rate ; Humans ; Long QT Syndrome ; complications ; congenital ; diagnosis ; therapy ; Male ; Risk Factors ; Seizures ; complications

OBJECTIVETo assess the feasibility, safety and effectiveness of video-assisted thoracoscopic sympathectomy (VATS) for the treatment of congenital long QT syndrome.

METHODSUnder general anaesthesia, pleural cavity was entered via two or three small incisions in the left intercostal space. The left thoracic sympathetic chain was identified and resected from T2 approximately T5. The lower one at the third of the left stellate ganglion was also resected.

RESULTSVATS resulted in a significant shortening in corrected QT intervals in three patients. The average QT interval of the four patients was 537.5 ms before VATS and 512.5 ms after VATS. The heart rate of the patients remained unchanged. There were no major peri-operative complications apart from mild ptosis of the left upper eyelid in one patient who recovered in the following days. The syndrome recurred in one patient in syncopal events in four months after VATS.

CONCLUSIONVATS is a safe as well as an effective technique for the treatment of congenital long QT syndromes.

Adult ; Child ; Female ; Humans ; Long QT Syndrome ; congenital ; surgery ; Male ; Sympathectomy ; methods ; Thoracic Surgery, Video-Assisted ; methods

OBJECTIVETo investigate the functional expression of HERG mutation A561V detected in a Chinese congenital long QT syndrome family.

METHODSThe mutation gene A561V was cloned into eukaryotic expressive vector pcDNA3 by quick site-directed mutagenesis PCR and restriction enzymes. The wild-type HERG, heterozygous type HERG and HERG mutation A561V were respectively cotransfected with pRK5-GFP into HEK293 cells by Suprefact transfection regent. The protein expression was measured by immunofluorescence method and Western blot. The electrophysiological characteristics of transfected cells were determined by whole cell patch-clamp technique.

RESULTSDirect sequence analyses revealed a C to T transition at position 1682. A561V mutation was correctly combined to eukaryotic expressive vector pcDNA3 and expressed in HEK293 cells. The protein expression of mutation and heterozygosis were located in cytoplasm and cellular membrane. 155 kDa and 135 kDa protein bands were detected in wild type HERG channel while only 135 kDa protein band was shown in heterozygous and mutational channels. Significant HERG tail-current was recorded in wild type HERG channel but not in mutation and heterozygosis channels.

CONCLUSIONThis study evidenced a functional dominant-negative current suppression in HEK293 cells transfected with HERG mutation A561V.

Cell Line ; DNA Mutational Analysis ; ERG1 Potassium Channel ; Ether-A-Go-Go Potassium Channels ; genetics ; Gene Expression ; Humans ; Long QT Syndrome ; congenital ; genetics ; Mutation ; Patch-Clamp Techniques ; Transfection

Anti-Arrhythmia Agents ; adverse effects ; therapeutic use ; Cardiomyopathies ; drug therapy ; Drug Interactions ; Heart Defects, Congenital ; drug therapy ; Humans ; Long QT Syndrome ; drug therapy

In order to assess the clinical manifestations and electrocardiogram (ECG) characteristics of Chinese long QT syndrome (LQTS) patients and describe the phenotype-genotype correlation, the subjects from 5 congenital LQTS families underwent clinical detailed examination including resting body surface ECG. QT interval and transmural dispersion of repolarization (TDR) were manually measured. Five families were genotyped by linkage analysis (polymerase chain reacting-short tandem repeat, PCR-STR). The phenotype-genotype correlation was analyzed. Four families were LQT2, 1 family was LQT3. Twenty-eight gene carriers were (14 males and 14 females) identified from 5 families. The mean QTc and TDRc were 0.56 +/- 0.04 s (range 0.42 to 0.63) and 0.16 +/- 0.04 s (range 0.09 to 0.24) respectively. 35.7% (10/28) had normal to borderline QTc (< or = 0.460 s). There was significant difference in QTc and TDRc between the patients with symptomatic LQTS and those with asymptomatic LQTS, and there was significant difference in TDRc between the asymptomatic patients and normal people also. A history of cardiac events was present in 50% (14/28), including 9 with syncope, 2 with sudden death (SD) and occurred in the absence of beta-blocker. Three SDs occurred prior to the diagnosis of LQTS and had no ECG record. Two out of 5 SDs (40%) occurred as the first symptom. Typical LQT2 T wave pattern were found in 40% (6/15) of all affected members. The appearing-normal T wave was found in one LQT3 family. Low penetrance of QTc and symptoms resulted in diagnostic challenge. ECG patterns and repolarization parameters may be used to predict the genotype in most families. Genetic test is very important for identification of gene carriers.
Arrhythmias, Cardiac ; etiology ; genetics ; Asian Continental Ancestry Group ; Electrocardiography ; Female ; Genotype ; Humans ; Long QT Syndrome ; complications ; congenital ; genetics ; Male ; Pedigree ; Phenotype

OBJECTIVETo construct the sodium channel gene SCN5A-delQKP1507-1509 mutation associated with congenital long QT syndrome, and its eukaryotic expression vector, and to examine the expression of mutation protein in human embryonic kidney (HEK) 293 cells.

METHODSEukaryotic expression vector PEGFP-delQKP-hH1 for SCN5A-delQKP1507-1509 mutation was constructed by rapid site-directed mutagenesis. HEK293 cells were transfected with the wild or mutant vector using lipofectamine, and then subjected to confocal microscopy. The transfected cells were immunostained to visualize intracellular expression of the mutant molecules.

RESULTSDirect sequence and electrophoresis analysis revealed 9 basic group absences at position 1507-1509. The delQKP1507-1509 mutation eukaryotic expression vector was expressed in HEK293 cells. Immunostaining of transfected cells showed the expression of both wild type and mutant molecules on the plasma membrane and there was no difference in the amount of protein, which suggested that the mutant delQKP1507-1509 did not impair normal protein expression in HEK293 cells.

CONCLUSIONSSuccessful construction of mutant SCN5AdelQKP1507-1509 eukaryotic expression vector and expression of SCN5A protein in HEK293 cells provides a basis for further study on the functional effects of congenital long QT syndrome as a cause of SCN5A mutation.

Blotting, Western ; HEK293 Cells ; Humans ; Long QT Syndrome ; congenital ; genetics ; Mutagenesis, Site-Directed ; NAV1.5 Voltage-Gated Sodium Channel ; analysis ; genetics ; physiology

Long QT syndrome (LQTs) is a rare congenital disorder of the heart's electrical activity. Patients with LQTs are at increased risk of developing fatal ventricular arrhythmias. Elevated levels of sympathetic stimulation can exacerbate this risk. Successful behavior management is indispensable in the treatment of patients with LQTs. However, many drugs involved in pharmacologic behavior management are known to adversely affect the QT interval. Therefore, careful selection of a sedative drug is essential in avoiding such incidences. A 10-year-old boy with a known diagnosis of LQTs required restorative treatment due to dental caries at the permanent molar. He required sedation since treatment was painful and dental phobia can trigger sympathetic stimulation, creating a dangerous situation for patients with LQTs. Therefore, the treatment was performed over two sessions under moderate sedation involving propofol combined with nitrous oxide. Restorative treatment was successful without any complications under sedation with a target-controlled infusion (TCI) of propofol. There was no significant QT prolongation during pulpal treatment. Propofol TCI may be a good candidate for sedation in patients with LQTs.
Arrhythmias, Cardiac ; Child ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Conscious Sedation* ; Dental Anxiety ; Dental Caries ; Diagnosis ; Humans ; Incidence ; Long QT Syndrome* ; Male ; Molar ; Nitrous Oxide ; Propofol*

Long QT syndrome (LQTs) is a rare congenital disorder of the heart's electrical activity. Patients with LQTs are at increased risk of developing fatal ventricular arrhythmias. Elevated levels of sympathetic stimulation can exacerbate this risk. Successful behavior management is indispensable in the treatment of patients with LQTs. However, many drugs involved in pharmacologic behavior management are known to adversely affect the QT interval. Therefore, careful selection of a sedative drug is essential in avoiding such incidences. A 10-year-old boy with a known diagnosis of LQTs required restorative treatment due to dental caries at the permanent molar. He required sedation since treatment was painful and dental phobia can trigger sympathetic stimulation, creating a dangerous situation for patients with LQTs. Therefore, the treatment was performed over two sessions under moderate sedation involving propofol combined with nitrous oxide. Restorative treatment was successful without any complications under sedation with a target-controlled infusion (TCI) of propofol. There was no significant QT prolongation during pulpal treatment. Propofol TCI may be a good candidate for sedation in patients with LQTs.
Arrhythmias, Cardiac ; Child ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Conscious Sedation* ; Dental Anxiety ; Dental Caries ; Diagnosis ; Humans ; Incidence ; Long QT Syndrome* ; Male ; Molar ; Nitrous Oxide ; Propofol*

OBJECTIVETo perform mutation analysis in a family with long QT syndrome.

METHODSThe medical record of the affected child and his parents were collected. The locus of gene associated with the long QT syndrome was mapped by linkage analysis. Mutation analysis was done by PCR-single strand conformation polymorphism (SSCP) and direct sequencing.

RESULTSA mutation (L539fs/47) and a SNP (L564L) were found in exon 7 of the KCNH2 gene of the proband. The mutation was from the father.

CONCLUSIONA novel mutation of L539fs/47 in the KCNH2 gene was identified in the LQTS family, which might be the disease-causing mutation for the family.

Base Sequence ; ERG1 Potassium Channel ; Ether-A-Go-Go Potassium Channels ; genetics ; Female ; Frameshift Mutation ; Humans ; Long QT Syndrome ; congenital ; genetics ; Male ; Molecular Sequence Data ; Pedigree ; Polymorphism, Single Nucleotide ; Young Adult