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.