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.


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.
Arnestad
Marianne
M
Institute of Forensic Medicine, University of Oslo, Oslo, Norway.
Crotti
Lia
L
Rognum
Torleiv O
TO
Insolia
Roberto
R
Pedrazzini
Matteo
M
Ferrandi
Chiara
C
Vege
Ashild
A
Wang
Dao W
DW
Rhodes
Troy E
TE
George
Alfred L
AL
Schwartz
Peter J
PJ
D000328:Adult; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000235:genetics; D016022:Case-Control Studies; D051244:Caveolin 3 / Q000235:genetics; D002675:Child, Preschool; D004562:Electrocardiography; D005260:Female; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008133:Long QT Syndrome / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009664:Norway; D015221:Potassium Channels / Q000235:genetics; D012307:Risk Factors; D016037:Single-Blind Method; D015222:Sodium Channels / Q000235:genetics; D013398:Sudden Infant Death / Q000209:etiology* / Q000235:genetics*
C417736:CAV3 protein, human; D051244:Caveolin 3; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015221:Potassium Channels; C568320:SCN5A protein, human; D015222:Sodium Channels