title: Postmortem review and genetic analysis in sudden infant death syndrome: an 11-year review.
abstract: 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.
authors.affiliation: Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, NSW 2042, Australia.
authors.forename: Angharad
authors.initials: A
authors.lastname: Evans
authors.forename: Richard D
authors.initials: RD
authors.lastname: Bagnall
authors.forename: Johan
authors.initials: J
authors.lastname: Duflou
authors.forename: Christopher
authors.initials: C
authors.lastname: Semsarian
mesh_terms: D001344:Autopsy; D001513:Beds; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007223:Infant; D007231:Infant, Newborn; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D015221:Potassium Channels; D013398:Sudden Infant Death / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C578710:HCN2 protein, human; C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009124:Muscle Proteins; D015221:Potassium Channels
keywords: Arrhythmia; HCN gene; Ion channel; Sudden infant death syndrome