The Role of the Cardiac Sodium Channel in Perinatal Early Infant Mortality.

KEY POINTS The cardiac sodium channel plays an important role in arrhythmias of genetic origin and is implicated in perinatal mortality. Channelopathies have been implicated in 15% of sudden infant death syndrome (SIDS) cases, and genetic variants with a functional effect on SCN5A or in sodium channel ancillary proteins are present in most of them. Genetic variants with a functional effect on long QT syndrome [LQTS] genes are present in 8.8% of intrauterine unexplained fetal death [IUFD] cases and SCN5A plays a major role. Patients with severe LQTS type 3 (LQT3) manifesting in the perinatal early infant period are associated with very marked QT prolongations, which make them easily identifiable by electrocardiogram screening in the first month of life, thus enhancing the chances of effective preventive therapies. There are differences between SCN5A mutations producing severe early-onset LQT3 and SIDS/ IUFD in terms of topology and frequency in the general population. This observation translates in pathophysiologic considerations