Potential role of QT interval prolongation in sudden infant death syndrome.

Maron, Barry J.; Clark, Chester E.; Goldstein, Robert E.; Epstein, S E

doi:10.1161/01.cir.54.3.423

Cited by 118 publications

(54 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 99%

Cardiac potassium channel dysfunction in sudden infant death syndrome

Wang

Desai

Crotti

et al. 2008

Journal of Molecular and Cellular Cardiology

100

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

Cardiac potassium channel dysfunction in sudden infant death syndrome

Wang

Desai

Crotti

et al. 2008

Journal of Molecular and Cellular Cardiology

100

View full text Add to dashboard Cite

show abstract

“…Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval on the electrocardiogram (ECG) and a major cause of malignant ventricular tachyarrhythmias (13,14). Association of SIDS and LQTS has been recognized since the first report in 1976 (15), and recent studies have demonstrated genetic link between SIDS and LQTS, suggesting that 2-10% of SIDS cases are attributable to the mutations in LQTS genes, especially in SCN5A (16 -24).…”

mentioning

confidence: 99%

Cardiac Ion Channel Gene Mutations in Sudden Infant Death Syndrome

et al. 2008

View full text Add to dashboard Cite

Sudden infant death syndrome (SIDS) is multifactorial and may result from the interaction of a number of environmental, genetic, and developmental factors. We studied three major genes causing long QT syndrome in 42 Japanese SIDS victims and found five mutations, KCNQ1-K598R, KCNH2-T895M, SCN5A-F532C, SCN5A-G1084S, and SCN5A-F1705S, in four cases; one case had both KCNH2-T895M and SCN5A-G1084S. All mutations were novel except for SCN5A-F532C, which was previously detected in an arrhythmic patient. Heterologous expression study revealed significant changes in channel properties of KCNH2-T895M, SCN5A-G1084S, and SCN5A-F1705S, but did not in KCNQ1-K598R and SCN5A-F532C. Our data suggests that nearly 10% of SIDS victims in Japan have mutations of the cardiac ion channel genes similar to in other countries.

show abstract

“…While recognized risk factors suggest that SIDS is a heterogeneous entity with multifactorial pathogenesis, the LQTS hypothesis [13,14] has continued to garner support in the cardiovascular field due to reports of prolongation of the QT interval in SIDS cases [15,16] and identification of mutations in the same ion channel genes that cause LQTS in SIDS postmortem genetic samples [17][18][19][20][21]. The epidemiologic significance of these findings is the subject of ongoing debate [22,23].…”

Section: Lqts and Sidsmentioning

confidence: 99%

Sudden infant death syndrome and long QT syndrome: The zealots versus the naysayers

Border

Benson²

2007

Heart Rhythm

View full text Add to dashboard Cite

"Fools rush in where angels fear to tread." -Alexander Pope, Essay on Criticism, 1711Sudden infant death syndrome (SIDS), a leading cause of infant death, have a disproportionate psychosocial and medicolegal impact because they usually occur in otherwise healthy babies. While many pathophysiologic mechanisms for SIDS have been proposed, including respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, none has caused as much controversy as the cardiac dysrhythmia hypothesis. The existence of an association between SIDS and the long QT syndrome (LQTS) has been at the heart of this debate for over 30 years. In this issue of Heart Rhythm, Cronk et al report the first molecular and functional evidence to implicate CAV3 as a pathogenic basis of SIDS [1]; how does this elegant study fit into the controversy? What is SIDS?The definition of SIDS originally appeared in 1969, but as a result of research in the field, was redefined as the sudden unexpected death of an infant <1 year of age, with onset of the fatal episode apparently occurring during sleep, that remains unexplained after a thorough investigation, including performance of a complete autopsy and review of the circumstances of death and the clinical history [2]. There has been a major decrease in the incidence of SIDS coincident with the American Academy of Pediatrics (AAP) release of recommendations in 1992 that infants be placed down for sleep in a nonprone position [3]. However, despite marked reductions in rates over the past decade, SIDS is still responsible for more infant deaths in the United States than any other cause of death during infancy beyond the neonatal period [4]. What is LQTS?LQTS is a heterogeneous disorder characterized by prolongation of the QT interval, multiform ventricular tachycardia (torsades de pointes), seizures, syncope, and sudden death; a positive family history of similar findings considerably aids the diagnosis. Of genes known to cause LQTS, 3 ion channels (KCNQ1 (LQTS1, ∼45%), KCNH2 (LQTS2, ∼45%), and SCN5A (LQTS3, ∼10%) are the most common. Mutations in ANK2 represent a nonchannel form of LQTS; mutations in CAV3 represent a second example [5]. Despite a designation as

show abstract

Potential role of QT interval prolongation in sudden infant death syndrome.

Cited by 118 publications

References 44 publications

Cardiac potassium channel dysfunction in sudden infant death syndrome

Cardiac potassium channel dysfunction in sudden infant death syndrome

Cardiac Ion Channel Gene Mutations in Sudden Infant Death Syndrome

Sudden infant death syndrome and long QT syndrome: The zealots versus the naysayers

Contact Info

Product

Resources

About