Spectrum of ST-T-wave pattern and repolarization parameters in congenital long-QT syndrome. ECG findings identify genotypes
ABSTRACT Congenital long-QT syndrome (LQTS) is caused by mutations of genes encoding the slow component of the delayed rectifier current (LQT1, LQT5), the rapid component of the delayed rectifier current (LQT2, LQT6), or the Na(+) current (LQT3), resulting in ST-T-wave abnormalities on the ECG. This study evaluated the spectrum of ST-T-wave patterns and repolarization parameters by genotype and determined whether genotype could be identified by ECG.
ECGs of 284 gene carriers were studied to determine ST-T-wave patterns, and repolarization parameters were quantified. Genotypes were identified by individual ECG versus family-grouped ECG analysis in separate studies using ECGs of 146 gene carriers from 29 families and 233 members of 127 families undergoing molecular genotyping, respectively. Ten typical ST-T patterns (4 LQT1, 4 LQT2, and 2 LQT3) were present in 88% of LQT1 and LQT2 carriers and in 65% of LQT3 carriers. Repolarization parameters also differed by genotype. A combination of quantified repolarization parameters identified genotype with sensitivity/specificity of 85%/70% for LQT1, 83%/94% for LQT2, and 47%/63% for LQT3. Typical patterns in family-grouped ECGs best identified the genotype, being correct in 56 of 56 (21 LQT1, 33 LQT2, and 2 LQT3) families with mutation results.
Typical ST-T-wave patterns are present in the majority of genotyped LQTS patients and can be used to identify LQT1, LQT2, and possibly LQT3 genotypes. Family-grouped ECG analysis improves genotype identification accuracy. This approach can simplify genetic screening by targeting the gene for initial study. The multiple ST-T patterns in each genotype raise questions regarding the pathophysiology and regulation of repolarization in LQTS.
- SourceAvailable from: Daniel Penny
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- "Unfortunately no medical records could be obtained. ECGs of the mother showed prolonged QTc (471-499 ms) with subtle bifid T waves in most of 12-leads, an ECG pattern typically seen in LQT2.   The proband's father had an IRBBB, borderline QTc (456-463 ms) with an atypical T wave morphology. Unlike their daughter, they had no structural cardiovascular abnormalities. "
ABSTRACT: Objective Patients with inherited long QT syndrome (LQTS) are prone to torsade de pointes and sudden death (SD). Identifying affected individuals is important for SD prevention. This study aimed to determine the cause and genotype-phenotype characteristics of LQTS in a large Omani family. Methods Upon LQTS diagnosis of a 5-year-old girl (proband), targeted mutation screening was performed based on the gene-specific ECG pattern identified in her mother. ECG-guided family genotyping was conducted for identifying additional affected individuals. Results ECGs of the proband demonstrated 2:1 AV block, incomplete right bundle branch block (IRBBB) and markedly prolonged QTc (571-638 ms) with bizarre T waves. Cardiac imaging revealed dilatation of the ascending aorta and pulmonary artery, and left ventricular non-compaction. Her parents were first cousins. Both showed mild QT prolongation, with the mother presenting a LQT2 T wave pattern and the father IRBBB. Targeted KCNH2 screening identified a novel homozygous frameshift mutation p.T1019Pfs × 38 in the proband within 72-hour. Family genotyping uncovered 3 concealed LQT2 and confirmed 11 members showing LQT2 ECG patterns as heterozygous mutation carriers. All heterozygous carriers were asymptomatic, with 71% showing normal to borderline prolonged QTc (458 ± 33 ms, range 409-522 ms). Conclusion p.T1019Pfs × 38, a novel KCNH2 mutation, has been identified in a large LQTS family in Oman. Consanguineous marriages resulted in a homozygous with severe LQTS. ECG-guided phenotyping and genotyping achieved a high efficiency. Genetic testing is essential in identifying concealed LQTS. Further investigation is warranted to determine if there is a causative relationship between homozygous p.T1019Pfs × 38 and cardiovascular anomaly.IJC Heart and Vessels 07/2014; 4. DOI:10.1016/j.ijchv.2014.06.001
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- "Typical ST-T-wave patterns are present in the majority of genotyped LQTS patients and can be used to identify LQTS1, LQTS2, and possibly LQTS3 genotypes (85, 86). "
ABSTRACT: Primary cardiac arrhythmias are often caused by defects, predominantly in the genes responsible for generation of cardiac electrical potential, i.e., cardiac rhythm generation. Due to the variability in underlying genetic defects, type, and location of the mutations and putative modifiers, clinical phenotypes could be moderate to severe, even absent in many individuals. Clinical presentation and severity could be quite variable, syncope, or sudden cardiac death could also be the first and the only manifestation in a patient who had previously no symptoms at all. Despite usual familial occurrence of such cardiac arrhythmias, disease causal genetic defects could also be de novo in significant number of patients. Long QT syndrome (LQTS) is the most eloquently investigated primary cardiac rhythm disorder. A genetic defect can be identified in ∼70% of definitive LQTS patients, followed by Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) and Brugada syndrome (BrS), where a genetic defect is found in <40% cases. In addition to these widely investigated hereditary arrhythmia syndromes, there remain many other relatively less common arrhythmia syndromes, where researchers also have unraveled the genetic etiology, e.g., short QT syndrome (SQTS), sick sinus syndrome (SSS), cardiac conduction defect (CCD), idiopathic ventricular fibrillation (IVF), early repolarization syndrome (ERS). There exist also various other ill-defined primary cardiac rhythm disorders with strong genetic and familial predisposition. In the present review we will focus on the genetic basis of LQTS and its clinical management. We will also discuss the presently available genetic insight in this context from Saudi Arabia.Frontiers in Pediatrics 11/2013; 1:39. DOI:10.3389/fped.2013.00039
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- "Now, at least 12 different genes are known to be related to this disease (6). There have been many researches that described the associations between the morphology of the ST-T complex and the genotype (22, 23). And risk stratification was performed for the specific genotype in many studies, but they revealed no significant contribution of genotype to outcome (17, 24). "
ABSTRACT: The long QT syndrome (LQTS) is a rare hereditary disorder in which affected individuals have a possibility of ventricular tachyarrhythmia and sudden cardiac death. We investigated 62 LQTS (QTc ≥ 0.47 sec) and 19 family members whose genetic study revealed mutation of LQT gene. In the proband group, the modes of presentation were ECG abnormality (38.7%), aborted cardiac arrest (24.2%), and syncope or seizure (19.4%). Median age of initial symptom development was 10.5 yr. Genetic studies were performed in 61; and mutations were found in 40 cases (KCNQ1 in 19, KCNH2 in 10, SCN5A in 7, KCNJ2 in 3, and CACNA1C in 1). In the family group, the penetrance of LQT gene mutation was 57.9%. QTc was longer as patients had the history of syncope (P = 0.001), ventricular tachycardia (P = 0.017) and aborted arrest (P = 0.010). QTc longer than 0.508 sec could be a cut-off value for major cardiac events (sensitivity 0.806, specificity 0.600). Beta-blocker was frequently applied for treatment and had significant effects on reducing QTc (P = 0.007). Implantable cardioverter defibrillators were applied in 6 patients. Congenital LQTS is a potentially lethal disease. It shows various genetic mutations with low penetrance in Korean patients.Journal of Korean medical science 10/2013; 28(10):1454-60. DOI:10.3346/jkms.2013.28.10.1454 · 1.25 Impact Factor