Contribution of Long-QT Syndrome Genes to Sudden Infant Death Syndrome

The precise mechanisms for SIDS, or “crib death,” are not known, although multiple hypotheses have been proposed over the years, including abnormal brainstem respiratory control of arousal, dysautonomia, and malignant cardiac bradyarrhythmias or tachyarrhythmias.2–4 Genetic, developmental, and environmental risk factors for SIDS have been identified, such as premature birth, multiple gestations, being the sibling of a SIDS victim, maternal illicit drug use, prone sleeping position or bed sharing, and history of apnea/ bradycardia or “near-miss SIDS” episodes.3–5 Investigators have suggested respiratory control regulatory abnormalities, neurological developmental defects, and cardiac rhythm disorders, including QT prolongation and ventricular arrhythmias, as underpinnings of SIDS. Supporting these various hypotheses are common autopsy findings such as petechial hemorrhages, pulmonary congestion, and developmental defects in the brainstem and neurotransmitters.4,5 Myriad diagnostic studies have been used for potential risk stratification of infants thought to be at higher risk for SIDS and have included electroencephalogram, pulse oximetry, 12-lead ECG, home apnea monitoring, and infant polysomnography sleep studies. The National Institutes of Health and the American Academy of Pediatrics have actively promoted the supine sleeping position for healthy term infants, and pediatricians have educated parents to put infants to sleep in the supine position. This simple recommendation has, at least in part, contributed to a significant reduction in the incidence of SIDS.6 Death from cardiac causes is uncommon in infancy and is most often the result of cardiac electrical diseases such as the congenital long-QT syndromes (LQTS), severe structural congenital heart disease, and metabolic cardiomyopathies. In infants without a known antemortem diagnosis or abnormalities identified at autopsy, “SIDS” becomes the default diagnosis and accounts for the majority of cases. Although SIDS is clearly multifactorial, the potential cardiac causes of some SIDS cases include rhythm disturbances and congenital LQTS. However, most SIDS victims have normal QT intervals, no antecedent history of arrhythmia symptoms, and no known family history of QT prolongation, LQTS, or sudden death.