Prevalence of long QT syndrome gene variants in sudden infant death syndrome.

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Prevalence of long-QT syndrome gene variants in sudden infant death syndrome.

Background—The hypothesis that some cases of sudden infant death syndrome (SIDS) could be caused by long-QT syndrome (LQTS) has been supported by molecular studies. However, there are inadequate data regarding the true prevalence of mutations in arrhythmia-susceptibility genes among SIDS cases. Given the importance and potential implications of these observations, we performed a study to more accurately quantify the contribution to SIDS of LQTS gene mutations and rare variants. Methods and Results—Molecular screening of 7 genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CAV3) associated with LQTS was performed with denaturing high-performance liquid chromatography and nucleotide sequencing of genomic DNA from 201 cases diagnosed as SIDS according to the Nordic Criteria, and from 182 infant and adult controls. All SIDS and control cases originated from the same regions in Norway. Genetic analysis was blinded to diagnosis. Mutations and rare variants were found in 26 of 201 cases (12.9%). On the basis of their functional effect, however, we considered 8 mutations and 7 rare variants found in 19 of 201 cases as likely contributors to sudden death (9.5%; 95% CI, 5.8 to 14.4%). Conclusions—We demonstrated that 9.5% of cases diagnosed as SIDS carry functionally significant genetic variants in LQTS genes. The present study demonstrates that sudden arrhythmic death is an important contributor to SIDS. As these variants likely modify ventricular repolarization and QT interval duration, our results support the debated concept that an ECG would probably identify most infants at risk for sudden death due to LQTS either in infancy or later on in life

Reclassification of SIDS cases - a need for adjustment of the San Diego classification?

A study was undertaken reclassifying cases of sudden infant death syndrome (SIDS) taken from two geographically separate locations utilizing the San Diego definition with subclassifications. One hundred twenty-eight infant cases were examined from files at Forensic Science South Australia in Adelaide, SA, Australia over a 7.5-year period from July 1999 to January 2007. Thirty-one cases (24%) had initially been diagnosed as SIDS and 30 (23%) as undetermined while 67 (52%) had an explainable cause of death. After reclassification, the number of SIDS cases had increased to 49 of the 128 cases, now representing 38% of the cases; category IB SIDS constituted 10 (20%) and II SIDS 39 (80%) of the SIDS cases. No cases were classified as IA SIDS. Two hundred eighteen infant cases were identified from the files of the Department of Forensic Medicine, Aarhus University, Denmark over a 16-year period from 1992 to 2007. Eighty-two (38%) were originally diagnosed as SIDS, 128 (59%) with identifiable causes of death, and 8 (4%) as unexplained. After review, 77 (35%) cases were reclassified as SIDS, a decrease of 6%. Twenty (26%) infants were classified as category IB SIDS and 57 (74%) as II SIDS. None of the cases met the criteria for IA SIDS. Problems arose in assessing cases with failure to thrive, fever, and possible asphyxia. Modifications to the San Diego subclassifications might improve the consistency of categorizing these cases.Lisbeth Lund Jensen, Marianne Cathrine Rohde, Jytte Banner, Roger William Byar