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
Inc.,
Published in Journal Watch Neurology August 23, 2000
Source
Schwartz PJ
et al. A molecular link between the sudden infant death
syndrome and the long-QT syndrome. N Engl J Med 2000 Jul 27 343 262 -267.