Prolonged QT interval and cardiac arrhythmias in two neonates: sudden infant death syndrome in one case.

Southall, D P; Arrowsmith, W A; Oakley, Jee; McEnery, G; Anderson, Robert H.; Shinebourne, E A

doi:10.1136/adc.54.10.776

Cited by 47 publications

(21 citation statements)

References 22 publications

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“…Life-threatening arrhythmias including the congenital long QT syndrome (LQTS) have been proposed to contribute to some cases of the sudden infant death syndrome (SIDS), the leading cause of death among infants 1 month to 1 year of age [1][2][3]. Supporting this theory are recent observations that mutations in genes responsible for LQTS are found in approximately 5-10% of SIDS cases [4][5][6].…”

Section: Introductionmentioning

confidence: 62%

Cardiac potassium channel dysfunction in sudden infant death syndrome

Wang

Desai

Crotti

et al. 2008

Journal of Molecular and Cellular Cardiology

100

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Life-threatening arrhythmias have been suspected as one cause of the sudden infant death syndrome (SIDS), and this hypothesis is supported by the observation that mutations in arrhythmia susceptibility genes occur in 5-10% of cases. However, the functional consequences of cardiac potassium channel gene mutations associated with SIDS and how these alleles might mechanistically predispose to sudden death are unknown. To address these questions, we studied four missense KCNH2 (encoding HERG) variants, one compound KCNH2 genotype, and a missense KCNQ1 mutation all previously identified in Norwegian SIDS cases. Three of the six variants exhibited functional impairments while three were biophysically similar to wild-type channels (KCNH2 variants V279M, R885C, S1040G). When coexpressed with WT-HERG, R273Q and K897T/R954C generated currents resembling the rapid component of the cardiac delayed rectifier current (I Kr ) but with significantly diminished amplitude. Action potential modeling demonstrated that this level of functional impairment was sufficient to evoke increased action potential duration and pausedependent early afterdepolarizations. By contrast, KCNQ1-I274V causes a gain-of-function in I Ks characterized by increased current density, faster activation, and slower deactivation leading to accumulation of instantaneous current upon repeated stimulation. Action potential simulations using a Markov model of heterozygous I274V-I Ks incorporated into the Luo-Rudy (LRd) ventricular cell model demonstrated marked rate-dependent shortening of action potential duration predicting a short QT phenotype. Our results indicate that certain potassium channel mutations associated with SIDS confer overt functional defects consistent with either LQTS or SQTS, and further emphasize the role of congenital arrhythmia susceptibility in this syndrome.

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Section: Introductionmentioning

confidence: 62%

Cardiac potassium channel dysfunction in sudden infant death syndrome

Wang

Desai

Crotti

et al. 2008

Journal of Molecular and Cellular Cardiology

100

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“…20 Besides conditions such as myocarditis, cardiomyopathy, and congenital heart disease, the LQTS has also been described as the underlying cause for death. 2,3,21 The majority of cardiac deaths caused by LQTS still occur in teenagers and adults. Deaths during the first months of life are uncommon.…”

Section: Discussionmentioning

confidence: 99%

De Novo Mutation in the SCN5A Gene Associated With Early Onset of Sudden Infant Death

et al. 2001

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Background — Congenital long QT syndrome (LQTS), a cardiac ion channel disease, is an important cause of sudden cardiac death. Prolongation of the QT interval has recently been associated with sudden infant death syndrome, which is the leading cause of death among infants between 1 week and 1 year of age. Available data suggest that early onset of congenital LQTS may contribute to premature sudden cardiac death in otherwise healthy infants. Methods and Results — In an infant who died suddenly at the age of 9 weeks, we performed mutation screening in all known LQTS genes. In the surface ECG soon after birth, a prolonged QTc interval (600 ms 1/2 ) and polymorphic ventricular tachyarrhythmias were documented. Mutational analysis identified a missense mutation (Ala1330Pro) in the cardiac sodium channel gene SCN5A , which was absent in both parents. Subsequent genetic testing confirmed paternity, thus suggesting a de novo origin. Voltage-clamp recordings of recombinant A1330P mutant channel expressed in HEK-293 cells showed a positive shift in voltage dependence of inactivation, a slowing of the time course of inactivation, and a faster recovery from inactivation. Conclusions — In this study, we report a de novo mutation in the sodium channel gene SCN5A , which is associated with sudden infant death. The altered functional characteristics of the mutant channel was different from previously reported LQTS3 mutants and caused a delay in final repolarization. Even in families without a history of LQTS, de novo mutations in cardiac ion channel genes may lead to sudden cardiac death in very young infants.

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“…Ventricular tachycardia may precede the syncopal attack (Benhorin and Medina, 1997) and sudden death in these patients. Although cardiac arrhythmia has been detected in a small number of fetuses with LQTS, most of these cases were associated with fetal bradycardia (Southall et al, 1979;Bharati et al, 1985;Presbitero et al, 1989;Vigliani, 1995;Trippel et al, 1995;Mache et al, 1996). We describe a neonate who presented with tachyarrhythmia in utero and in whom LQTS was diagnosed postnatally.…”

Section: Introductionmentioning

confidence: 92%