Postmortem review and genetic analysis in sudden infant death syndrome: an 11-year review

Sudden infant death syndrome (SIDS) is the unexpected death of a child younger than 1 year that remains unexplained after thorough evaluation. The possibility of an underlying primary arrhythmogenic disorder has been proposed as a potential cause of SIDS. This study sought to review SIDS deaths and to perform genetic analysis in key genes that may contribute to sudden death. From 2000 to 2010, all postmortem records from the Department of Forensic Medicine in Sydney, Australia, were reviewed. Cases that gave the cause of death as "SIDS" or "undetermined" but consistent with SIDS were included. In a subset of cases, the hyperpolarization-activated cyclic nucleotide (HCN)-gated channel family of genes (HCN2 and HCN4) was analyzed. A total of 226 SIDS cases were identified; 61% were male, 41% occurred while bed sharing, and there was a peak in deaths between 2 and 4 months old. The incidence did not decrease over the study period. In a subgroup of SIDS cases (n = 46), genetic analysis identified 2 likely pathogenic variants (2/46; 4%). A novel nonsynonymous variant, HCN4-Ala195Val, predicted to be pathogenic, was identified in a female infant who died at age 4 months. A female infant aged 5 weeks carried a rare nonsynonymous variant, HCN4-Val759Ile, which is similar to previously described variants associated with cardiac arrhythmias. In conclusion, the incidence of SIDS remains constant, with no apparent decline in the last decade. The underlying cause of SIDS remains largely unknown. Mutations in cardiac ion channel genes including rare nonsynonymous HCN gene variants may play a role in the pathogenesis of some SIDS cases.