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.

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Background— Mutations in genes responsible for the congenital long-QT syndrome, especially SCN5A , have been identified in some cases of sudden infant death syndrome. In a large-scale collaborative genetic screen, several SCN5A variants were identified in a Norwegian sudden infant death syndrome cohort (n=201). We present functional characterization of 7 missense variants (S216L, R680H, T1304M, F1486L, V1951L, F2004L, and P2006A) and 1 in-frame deletion allele (delAL586-587) identified by these efforts. Methods and Results— Whole-cell sodium currents were measured in tsA201 cells transiently transfected with recombinant wild-type or mutant SCN5A cDNA (hH1) coexpressed with the human β1 subunit. All variants exhibited defects in the kinetics and voltage dependence of inactivation. Five variants (S216L, T1304M, F1486L, F2004L, and P2006A) exhibited significantly increased persistent sodium currents (range, 0.5% to 1.7% of peak current) typical of SCN5A mutations associated with long-QT syndrome. These same 5 variants also displayed significant depolarizing shifts in voltage dependence of inactivation (range, 5 to 14 mV) and faster recovery from inactivation, but F1486L uniquely exhibits a depolarizing shift in the conductance-voltage relationship. Three alleles (delAL586-587, R680H, and V1951L) exhibited increased persistent current only under conditions of internal acidosis (R680H) or when expressed in the context of a common splice variant (delQ1077), indicating that they have a latent dysfunctional phenotype. Conclusions— Our present results greatly expand the spectrum of functionally characterized SCN5A variants associated with sudden infant death syndrome and provide further biophysical correlates of arrhythmia susceptibility in this syndrome.

Cerebrospinal fluid (CSF) from 20 infants who died of sudden infant death syndrome (SIDS), 7 cases of infectious death and 5 cases of violent death were examined with respect to concentrations of interleukin-6 (IL-6). The measurements were performed by ELISA. IL-6 levels in SIDS were significantly lower than in infectious death (p < 0.02), but significantly higher than in violent death (p < 0.02). Since IL-6 plays an important role in immune responses and may induce fever, the findings may suggest that immune activation plays a role in SIDS. The presence of cytokines in the central nervous system (CNS) may cause respiratory depression, especially in vulnerable infants.

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Aim-To look for changes in risk factors for sudden infant death syndrome (SIDS) after decrease and stabilisation of the SIDS rate. Methods-Questionnaires were distributed to parents of 174 SIDS infants, dying between 1984 and 1998, and 375 age and sex matched controls in southeast Norway. Results-The proportion of infants sleeping prone has decreased, along with the decrease in SIDS rate for the region during the periods studied, but over half of the SIDS victims are still found in the prone position. As the number of SIDS cases has decreased, additional risk factors have become more significant. Thus, after 1993, a significantly increased risk of SIDS is seen when the mother smokes during pregnancy. After 1993, young maternal age carries an increased risk. Maternal smoking and young maternal age are associated with each other. For SIDS victims, an increase in the number of infants found dead while co-sleeping is seen, and the age peak between 2 and 4 months and the winter peak have become less pronounced. Conclusion-Changes in risk factor profile following the decrease in SIDS rate in the early 1990s, as well as consistency of other factors, provides further clues to SIDS prevention and to the direction of further studies of death mechanisms. (Arch Dis Child 2001;85:108-115)

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