The sudden infant death syndrome (SIDS) is distressingly common. Despite a 30 percent decline between 1991 and 1995 for unknown reasons, the current incidence is 1/1000 during the first year of life. Etiologic possibilities include autonomic dysfunction, infection, and prone positioning. Direct physiologic observations of the event are exceedingly rare and have led to the general belief that ventricular fibrillation is not a likely precipitant.
In this case report, a 6-week-old infant in previously good health was found cyanotic and pulseless. Rapid resuscitation was instituted with correction of ventricular fibrillation and restoration of sinus rhythm. Marked QTc prolongation, a cardiac repolarization abnormality associated with ventricular arrhythmias and sudden death, was observed. Genetic analysis revealed a mutation in SCN5A, the cardiac sodium-channel gene. This mutation results in a prolongation of cardiac depolarization and is associated with a heritable form of QT-interval prolongation (i.e., the LQT3 subtype). Both parents tested negative for this variant, so the child had a spontaneous mutation. Insertion of the mutated cloned channel into frog oocytes increased a long-latency inward sodium current. In the heart, this current would prolong cardiac depolarization, providing circumstantial evidence for the pathophysiologic effect of the mutation.
Comment: This report offers valuable insight into the etiology of sudden death. Long-QT syndromes (LQTSs) are uncommon, however, and probably contribute only slightly to the incidence of SIDS. Simple ECG screening can detect them, and, as in this case, many can be effectively treated with propranolol and mexilitene. However, a lack of consensus about normative QTc data for infants may result in a high incidence of false-positive cases. Over the first year of life, the QTc should normalize; lack of normalization could be used to detect infants at risk.
Intriguingly, this child's QTc was still substantially prolonged at age 3; no episodes of symptomatic ventricular arrhythmia were reported. Whether asymptomatic episodes could have been detected by Holter monitoring is not clear. This raises the possibility that, in addition to the structural abnormality in the cardiac sodium channel, a precipitating event may be needed to initiate an arrhythmia. Speculation regarding sudden increases in cardiac sympathetic tone is appropriate because some LQTS-associated arrhythmias may be prevented with the use of a beta-blocker. In addition, in some forms of LQTS, QTc prolongation and ventricular arrhythmias occur only during startle or stress. Clearly, the role of the autonomic nervous system both in SIDS and LTQS cannot be ignored.
— S Oppenheimer
Stephen Oppenheimer, MD, PhD, is Director, Neuroscience, Pharmanet
Published in Journal Watch Neurology August 23, 2000