Electrocardiographic Prediction of Abnormal Genotype in Congenital Long QT Syndrome: Experience in 101 Related Family Members

Kaufman, Elizabeth S.; Priori, Silvia G.; Napolitano, Carlo; Schwartz, Peter J.; Iyengar, Sudha K.; Elston, Robert C.; Schnell, Audrey H.; Gorodeski, Eiran Z.; Rammohan, Guhan; Bahhur, Nael O.; Connuck, David; Verrilli, Linda; Rosenbaum, David S.; Brown, Arthur M.

doi:10.1046/j.1540-8167.2001.00455.x

Cited by 77 publications

(50 citation statements)

References 26 publications

(6 reference statements)

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“…6 Overt T-wave alternansgrossly visible beat-to-beat variation in T-wave amplitude and/or polarity-is viewed as an important prognostic indicator for TdP and sudden cardiac death in LQTS patients, but appears less frequently (2.5% to 7% of LQTS study participant samples) than microvoltage T-wave alternans (identifiable only by special signal processing-18 to 45% of LQTS patient groups undergoing specialized testing). 48 Another repolarization parameter, QT dispersion-the difference between the maximum and minimum QT values across the 12 standard ECG leads-has led to inconsistent results in distinguishing symptomatic from asymptomatic patient groups and fails to take into account T-wave morphology. 49 …”

Section: Clinical Evaluation and Laboratory Testing Phenotypic Ascertmentioning

confidence: 99%

The long QT syndrome family of cardiac ion channelopathies: A HuGE review

Modell

Lehmann

2006

Genetics in Medicine

146

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Long QT syndrome (LQTS) refers to a group of "channelopathies"-disorders that affect cardiac ion channels. The "family" concept of syndromes has been applied to the multiple LQTS genotypes, LQT1-8, which exhibit converging mechanisms leading to QT prolongation and slowed ventricular repolarization. The 470ϩ allelic mutations induce loss-of-function in the passage of mainly K ϩ ions, and gain-of-function in the passage of Na ϩ ions through their respective ion channels. Resultant early after depolarizations can lead to a polymorphic form of ventricular tachycardia known as torsade de pointes, resulting in syncope, sudden cardiac death, or near-death (i.e., cardiac arrest aborted either spontaneously or with external defibrillation). LQTS may be either congenital or acquired. The genetic epidemiology of both forms can vary with subpopulation depending on the allele, but as a whole, LQTS appears in every corner of the globe. Many polymorphisms, such as HERG P448R and A915V in Asians, and SCN5A

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Section: Clinical Evaluation and Laboratory Testing Phenotypic Ascertmentioning

confidence: 99%

The long QT syndrome family of cardiac ion channelopathies: A HuGE review

Modell

Lehmann

2006

Genetics in Medicine

146

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“…For 20 years, an LQT2 family has been studied extensively by our multidisciplinary group (14,15). Initial genotype testing of living family members following the sudden death of a 31-year-old female with a history of syncope along with the subsequent LQT2 diagnosis in a paternal aunt revealed a C→T nucleotide substitution at position 2,254 in exon 9 of KCNH2 resulting in the hERG R752W missense mutation.…”

Section: Introductionmentioning

confidence: 99%

“…Yet, a study performed on this large Cleveland LQT2 family carrying the hERG R752W mutation demonstrated that even in this homogeneous LQTS population, the phenotype was so variable that detailed clinical and ECG analyses did not permit an accurate diagnosis of gene carrier status. In fact, there was substantial overlap (78%) of QTc among subjects with and without the mutation, suggesting the presence of 1 or more modifier genes (14). We deployed a novel strategy combining the use of patient-derived iPSC-CMs alongside exome sequencing and genome editing to unravel novel electrophysiological arrhythmogenic mechanisms and identify new Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Physiological genomics identifies genetic modifiers of long QT syndrome type 2 severity

Chai¹,

Wan²,

Ramirez‐Navarro³

et al. 2018

Journal of Clinical Investigation

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“…Twenty primary studies 28,[32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] reported sensitivity and specificity estimates by using ECG to detect LQTS and/or HCM,…”

Section: Characteristics Of Reviewed Studiesmentioning

confidence: 99%

“…13 When incorporating Kobza, the summary prevalence increased fivefold to 38 per 100 000 (95% CI: 19-58) and heterogeneity increased (I 2 = 99%, P , .001). [42][43][44][45][46][47][48][49][50] The Bayesian sensitivity analysis giving the Schwartz 13 prior a low weight (1/2500) resulted in similar 48 Genotyped probands and relatives Not specified To provide clinical context, we used the summary phenotypic prevalence estimate for LQTS and 2 illustrative points (the maximal accuracy point and the maximal specificity point) on the HSROC curve for detection of LQTS by using ECG (Table 3). For both points, the NPV was near 100%.…”

Section: Long Qt Syndromementioning

confidence: 99%

Electrocardiogram Screening for Disorders That Cause Sudden Cardiac Death in Asymptomatic Children: A Meta-analysis

et al. 2012

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BACKGROUND AND OBJECTIVES: Pediatric sudden cardiac death (SCD) occurs in an estimated 0.8 to 6.2 per 100 000 children annually. Screening for cardiac disorders causing SCD in asymptomatic children has public appeal because of its apparent potential to avert tragedy; however, performance of the electrocardiogram (ECG) as a screening tool is unknown. We estimated (1) phenotypic (ECG-or echocardiogram [ECHO]-based) prevalence of selected pediatric disorders associated with SCD, and (2) sensitivity, specificity, and predictive value of ECG, alone or with ECHO. METHODS:We systematically reviewed literature on hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), and Wolff-ParkinsonWhite syndrome, the 3 most common disorders associated with SCD and detectable by ECG. RESULTS:We identified and screened 6954 abstracts, yielding 396 articles, and extracted data from 30. Summary phenotypic prevalences per 100 000 asymptomatic children were 45 (95% confidence interval [CI]: 10-79) for HCM, 7 (95% CI: 0-14) for LQTS, and 136 (95% CI: 55-218) for Wolff-Parkinson-White. The areas under the receiver operating characteristic curves for ECG were 0.91 for detecting HCM and 0.92 for LQTS. The negative predictive value of detecting either HCM or LQTS by using ECG was high; however, the positive predictive value varied by different sensitivity and specificity cut-points and the true prevalence of the conditions. CONCLUSIONS:Results provide an evidence base for evaluating pediatric screening for these disorders. ECG, alone or with ECHO, was a sensitive test for mass screening and negative predictive value was high, but positive predictive value and false-positive rates varied.

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Electrocardiographic Prediction of Abnormal Genotype in Congenital Long QT Syndrome: Experience in 101 Related Family Members

Cited by 77 publications

References 26 publications

The long QT syndrome family of cardiac ion channelopathies: A HuGE review

The long QT syndrome family of cardiac ion channelopathies: A HuGE review

Physiological genomics identifies genetic modifiers of long QT syndrome type 2 severity

Electrocardiogram Screening for Disorders That Cause Sudden Cardiac Death in Asymptomatic Children: A Meta-analysis

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