Q-T Prolongation and ventricular arrhythmias, with and without deafness, in the same family

Mathews, Emmett C.; Blount, Alston W.; Townsend, Jack

doi:10.1016/0002-9149(72)90174-9

Cited by 65 publications

(23 citation statements)

References 25 publications

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“…6 15 17 18 22 25 28 30 32 33 35-37 44 46 62 63The pauses eventually leading to torsade de pointes were mainly “compensatory pauses” following extrasystoles. These post-extrasystolic pauses were observed in 28 patients reported by others3 6 7 13 15 18 19 21-23 25 26 28 30-33 35 37 42-46 48-50 62and in all but two of the patients reported by us 2. In all, post-extrasystolic pauses, sudden sinus pauses, or both, preceded the onset of torsade de pointes in 73%, 14%, and 15% of all patients with pause dependent arrhythmias, respectively.…”

Section: Resultsmentioning

confidence: 62%

Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent?

Viskin

Fish

Zeltser

et al. 2000

Heart

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Objective-To determine the frequency and predictors of pause dependent torsade de pointes among patients with the congenital long QT syndrome and spontaneous ventricular tachyarrhythmias. Design-The literature on the "congenital long QT" was reviewed. Articles with illustrations demonstrating the onset of spontaneous polymorphic ventricular arrhythmias in the absence of arrhythmogenic drugs were included. Results-Illustrations of 62 spontaneous episodes of torsade de pointes among patients with congenital long QT syndrome were found in the literature. The majority (74%) of documented arrhythmias were "pause dependent"; 82% of these pauses were longer than the basic cycle length by > 100 ms. Age and sex correlated with the mode of arrhythmia initiation. Arrhythmias in infants (< 3 years old) were not pause dependent, while female sex correlated with pause dependent torsade. Using multivariate analysis, age was the only independent predictor of the mode of onset of torsade de pointes. Conclusion-Available data suggest that the majority of spontaneous arrhythmias in the congenital long QT syndrome are pause dependent. Torsade de pointes that is not preceded by pauses appears to be limited to patient subgroups with severe forms of the disease, like symptomatic infants. These findings have important implications regarding the use of cardiac pacing for arrhythmia prevention. (Heart 2000;83:661-666)

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Section: Resultsmentioning

confidence: 62%

Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent?

Viskin

Fish

Zeltser

et al. 2000

Heart

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“…The previous description of a family with QT prolongation and only partial hearing loss 29 prompted the performance of an audiogram test on the proband that, being completely normal, ruled out even a mild form of the Jervell and Lange-Nielsen syndrome. The cardiac phenotype characterized by QT prolongation and arrhythmias of both Romano-Ward and Jervell and Lange-Nielsen LQTS is currently considered to be inherited as a dominant trait.…”

Section: A Romano-ward Family Without Dominant Inheritancementioning

confidence: 99%

A Recessive Variant of the Romano-Ward Long-QT Syndrome?

et al. 1998

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Background-The congenital long-QT syndrome (LQTS) is a genetically heterogeneous disease characterized by prolonged ventricular repolarization and life-threatening arrhythmias. Mutations of the KVLQT1 gene, a cardiac potassium channel, generate two allelic diseases: the Romano-Ward syndrome, inherited as a dominant trait, and the Jervell and Lange-Nielsen syndrome, inherited as an autosomal recessive trait. Methods and Results-A consanguineous family with the clinical phenotype of LQTS was screened for mutations in the KVLQT1 gene. Complementary RNAs for injection into Xenopus oocytes were prepared, and currents were recorded with the double microelectrode technique. A homozygous missense mutation, leading to an alanine-to-threonine substitution at the beginning of the pore domain of the KVLQT1 channel, was found in the proband, a 9-year-old boy with normal hearing, a prolonged QT interval, and syncopal episodes during physical exercise. The parents of the proband were heterozygous for the mutation and had a normal QT interval. The functional evaluation of the mutant channel activity showed reduction in total current, a hyperpolarizing shift in activation, and a faster activation rate consistent with a mild mutation likely to require homozygosity to manifest the phenotype. Conclusions-These findings provide the first evidence for a recessive form of the Romano-Ward long-QT syndrome and indicate that homozygous mutations on KVLQT1 do not invariably produce the Jervell and Lange-Nielsen syndrome. The implications of this observation prompt a reconsideration of the penetrance of different mutations responsible for LQTS and suggest that mild mutations in LQTS genes may be present among the general population and may predispose to drug-induced ventricular arrhythmias. (Circulation. 1998;97:2420-2425.)

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“…Once considered a rare entity, genetic analysis has facilitated recognition of the congenital LQT syndromes with increasing frequency. Additionally, families have been described in which both syndromes occur together (30,39,57).…”

Section: Qt-syndrome -Aktueller Stand Molekulargenetischer Ergebnissementioning

confidence: 99%

“…In 1972, Mathews and co-workers already reported a LQT family with an autosomal dominant co-inheritance of QTc prolongation and deafness ("autosomal dominant JLN syndrome") (30). Very recently, Priori and co-workers reported on a LQT1 patient with a homozygous KCNQ1 mutation, but without inner ear deafness (38).…”

Section: Molecular Genetics Of the Lqt Syndromesmentioning

confidence: 99%

The LQT syndromes – current status of molecular mechanisms

et al. 1999

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Our knowledge on the molecular genetics of inherited cardiac arrhythmias is very recent in comparison to the advances of genetics achieved in other inherited cardiac disorders. This is related to the high mortality and early disease onset of these arrhythmias resulting in mostly small nucleus families. Thus, traditional genetic linkage studies that are based on the genetic information obtained from large multi-generation families were made difficult. In 1991, the first chromosomal locus for congenital long-QT (LQT) syndrome was identified on chromosome 11p15.5 (LQT1 locus) by linkage analysis. Meanwhile, the disease-causing gene at the LQT1 locus (KCNQ1), a gene encoding a K+ channel subunit of the IKs channel, and three other, major genes, all encoding cardiac ion channel components, have been identified. Taken together, LQT syndrome turned out to be a heterogeneous channelopathy. Moreover, the power of linkage studies to reveal the genetic causes of the LQT syndrome was also important to identify unknown but fundamental channel components that contribute to the ion currents tuning ventricular repolarization. In-vitro expression of the altered ion channel genes demonstrated in each case that the altered ion channel function produces prolongation of the action potential and thus the increasing propensity to ventricular tachyarrhythmias. Since these ion channels are pharmacological targets of many antiarrhythmic (and other) drugs, individual and potentially deleterious drug responses may be related to genetic variation in ion channel genes. Very recently, also in acquired LQT syndrome, which is a frequent clinical disorder in cardiology a genetic basis has been proposed in part since mutations in LQT genes have been specifically found. The discovery of ion channel defects in LQT syndrome represents the major achievement in our understanding and implies potential therapeutic options. The knowledge of the genomic structure of the LQT genes now offers the possibility to detect the underlying genetic defect in 80-90% of all patients. With this specific information, containing the type of ion channel (Na+ versus K+ channel) and electrophysiological alteration by the mutation (loss-of-function versus change-of-function mutation), gene-directed, elective drug therapies have been initiated in genotyped LQT patients. Based on preliminary data, that were supported by in vitro studies, this approach may be useful in recompensating the characteristic phenotypes in some LQT patients. Mutation detection is a new diagnostic tool which may become of more increasing importance in patients with a normal QTc or just a borderline prolongation of the QTc interval at presentation. These patients represent approximately 40% of all familial cases. Moreover, LQT3 syndrome and idiopathic ventricular fibrillation are allelic disorders and genetically overlap. In both mutations in the LQT3 gene SCN5A encoding the Na+ channel alpha-subunit for INa have been reported. Thus, the clinical nosology of inherited arrhythmias may be reconsidered aft...

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Q-T Prolongation and ventricular arrhythmias, with and without deafness, in the same family

Cited by 65 publications

References 25 publications

Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent?

Arrhythmias in the congenital long QT syndrome: how often is torsade de pointes pause dependent?

A Recessive Variant of the Romano-Ward Long-QT Syndrome?

The LQT syndromes – current status of molecular mechanisms

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