Sudden unexpected death in the young (SUDY) refers to non-traumatic sudden unexpected death of a seemingly healthy individual less than 40 years of age with no identified cause of death at autopsy. A thorough investigation that includes an autopsy leads to a diagnosis in most cases; however, 30% of young adults and up to 80% of infant and child cases remain undetermined (autopsy-negative). Molecular genetic testing has shown that nearly 40% of autopsy-negative SUDY cases are due to inherited arrhythmia syndromes (IAS). Genetic testing however is not routinely included in SUDY investigations. Our previous work has identified heterogeneity in SUDY death investigation practices, supporting the need for specific SUDY investigation protocols, post mortem tissue retention and written recommendations for SUDY-affected relatives. Presently, we have developed recommendations for coroners and medical examiners to inform the process of SUDY investigation in Canada.
Through collaboration with the Manitoba Medical Examiner’s Office to assist with diagnosis in 191 autopsy-negative child SUD cases, we have designed a cost-effective genetic testing approach. Our sequencing panel incorporates 70 genes including IAS candidate genes as well as other genes not previously investigated for IAS susceptibility and costs less than $500 per case. We have uncovered known SNPs, (e.g. KCNE1 S38G, ADCY9 I772M, AKAP6 N2035D and MYBPC3 I633V) and novel variants (e.g. TNNI1 R37C) which will be functionally characterized in our laboratory. All mutations known to be associated with IAS are reported to the ME’s office, which contacts SUDY-affected families to refer them for clinical assessment. Best practices from this study, as well as recommendations from our recent Public Health Agency of Canada report (“A National Strategy for the Prevention of Sudden Death in the Young”), and international expert’s published guidelines were used to develop recommendations for coroners and medical examiners to inform the process of SUDY investigation in Canada. The recommendations include a SUDY investigation protocol for scene investigators, protocols for tissue retention and storage, and prioritization of referral of first-degree relatives for clinical assessment.
Our cost-effective genetic testing panel that has successfully identified both novel and known genetic variants to assist in diagnosis of autopsy-negative child SUD cases. From our present and previous work as well as other published guidelines, we have developed recommendations for coroners and medical examiners to reduce heterogeneity and inform the process of SUDY death investigation practices in Canada.
The March of Dimes Foundation
© 2015 Published by Elsevier Inc.