ReviewSerotonin gene variants are unlikely to play a significant role in the pathogenesis of the sudden infant death syndrome

- Discussion of the evidence for a role of 5-HT gene variants in the pathogenesis of SIDS.
- Unique correlation of 5-HT neurochemistry with genotype in the same SIDS cases.
- 5-HT gene variants studied to date do not appear to play a major role in the pathogenesis of SIDS.
- SIDS is likely to be polygenic.
- Pathogenesis potentially involves rare point mutations and copy number variations.

Sudden infant death syndrome (SIDS) is defined as the sudden and unexpected death of an infant less than 12 months of age that is related to a sleep period and remains unexplained after a complete autopsy, death scene investigation, and review of the clinical history. The cause of SIDS is unknown, but a major subset of SIDS is proposed to result from abnormalities in serotonin (5-HT) and related neurotransmitters in regions of the lower brainstem that result in failure of protective homeostatic responses to life-threatening challenges during sleep. Multiple studies have implicated gene variants that affect different elements of 5-HT neurotransmission in the pathogenesis of these abnormalities in SIDS. In this review I discuss the data from these studies together with some new data correlating genotype with brainstem 5-HT neurochemistry in the same SIDS cases and conclude that these gene variants are unlikely to play a major role in the pathogenesis of the medullary 5-HT abnormalities observed in SIDS.