Cardiac Ion Channel Gene Mutations in Sudden Infant Death Syndrome

Otagiri, Tesshu; Kijima, Kazuki; Osawa, Motoki; Ishii, Kuniaki; Makita, Naomasa; Matoba, Ryoji; Umetsu, Kazuo; Hayasaka, Kiyoshi

doi:10.1203/pdr.0b013e3181841eca

Cited by 92 publications

(66 citation statements)

References 46 publications

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“…3,[5][6][7][8][9][10][11] For example, recent progress in molecular biology has clarified that LQTS partly contributes to sudden infant death syndrome (SIDS). 12,13 Unfortunately, prenatal diagnosis of LQTS has been extremely difficult to confirm except for a limited number of cases for which prenatal gene screening 14 or fetal magnetocardiography (fMCG) [15][16][17] was applied.…”

mentioning

confidence: 99%

Clinical Characteristics and Genetic Background of Congenital Long-QT Syndrome Diagnosed in Fetal, Neonatal, and Infantile Life

Horigome

Nagashima

Sumitomo

et al. 2010

Circ: Arrhythmia and Electrophysiology

108

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Background-Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence. Methods and Results-Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (nϭ18), the neonatal period (nϭ31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (nϭ9). Clinical presentation of LQTS included sinus bradycardia (nϭ37), ventricular tachycardia/torsades de pointes (nϭ27), atrioventricular block (nϭ23), family history of LQTS (nϭ21), sudden cardiac death/aborted cardiac arrest (nϭ14), convulsion (nϭ5), syncope (nϭ5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (nϭ11), LQT2 (nϭ11), LQT3 (nϭ6), and LQT8 (nϭ1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (nϭ14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of ␤-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator. Conclusions-Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded. (Circ Arrhythm Electrophysiol. 2010;3:10-17.)

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mentioning

confidence: 99%

Clinical Characteristics and Genetic Background of Congenital Long-QT Syndrome Diagnosed in Fetal, Neonatal, and Infantile Life

Horigome

Nagashima

Sumitomo

et al. 2010

Circ: Arrhythmia and Electrophysiology

108

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“…Regarding the 3 cases of infant death, the role of LQTS in the sudden infant death syndrome has been much debated. [22][23][24][25] Although it has been shown in a large study that LQTS mutations were present in 19 of 201 cases (9.5%) of sudden infant death syndrome, only 2 of the 15 genetic alterations identified were KCNQ1 mutations, each present in 1 case of sudden infant death syndrome, corresponding to a presence of KCNQ1 mutations in sudden infant death syndrome cases of a modest 1% (2 of 201). 22 The absence of an increased mortality below the age of 40 years in nonmedicated MCs, OCs, and their siblings implies that the 1.25% cumulative incidence of life-threatening cardiac events observed in the Swedish Y111C mutation carriers is not merely a reflection of successful ␤-blocker therapy.…”

Section: Benign Natural History 1873 To 1968mentioning

confidence: 96%

Low Incidence of Sudden Cardiac Death in a Swedish Y111C Type 1 Long-QT syndrome Population

Winbo

Diamant

Stattin

et al. 2009

Circ Cardiovasc Genet

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Background-A 10% cumulative incidence and a 0.3% per year incidence rate of sudden cardiac death in patients younger than 40 years and without therapy have been reported in type 1 long-QT syndrome. The Y111C-KCNQ1 mutation causes a severe phenotype in vitro, suggesting a high-risk mutation. This study investigated the phenotype among Y111C-KCNQ1 mutation carriers in the Swedish population with a focus on life-threatening cardiac events. Methods and Results-We identified 80 mutation carriers in 15 index families, segregating the Y111C-KCNQ1 mutation during a national inventory of mutations causing the long-QT syndrome. Twenty-four mutation carriers Ͻ40 years experienced syncope (30%). One mutation carrier had an aborted cardiac arrest (1.25%). No case of sudden cardiac death was reported during a mean nonmedicated follow-up of 25Ϯ20 years. This corresponds to a low incidence rate of life-threatening cardiac events (0.05%/year versus 0.3%/year, Pϭ0.025). In 8 Y111C families connected by a common ancestor, the natural history of the mutation was assessed by investigating the survival over the age of 40 years for 107 nonmedicated ascertained mutation carriers (nϭ24) and family members (nϭ83) born between 1873 and 1968. In total, 4 deaths in individuals younger than 40 years were noted: 1 case of noncardiac death and 3 infant deaths between 1873 and 1915. Conclusions-The dominant-negative Y111C-KCNQ1 mutation, associated with a severe phenotype in vitro, presents with a low incidence of life-threatening cardiac events in a Swedish population. This finding of discrepancy emphasizes the importance of clinical observations in the risk stratification of long-QT syndrome. (Circ Cardiovasc Genet. 2009;2:558-564.)

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“…Channelopathies are dysfunctional myocyte ion channels that result in abnormal movement of electrolytes into and/or out of the cell and predispose the heart to arrhythmia. [492][493][494][495][496][497][498][499][500][501] Mutations causing cardiac ion channelopathies are found in 2% to 10% of victims [492][493][494][495][496][497][498] and in 14% to 20% of young adults with sudden death in whom the cause of death is not evident in a routine autopsy. 499 -501 Clinical and laboratory (eg, ECG, molecular-genetic screening) investigations of first-and second-degree relatives of patients with sudden unexplained death reported inherited, arrhythmogenic disease in 22% to 53% of families.…”

Section: Sudden Unexplained Deathsmentioning

confidence: 99%