This article reports on a study that sequenced full exons of 84 genes associated with sudden death (SD) in the largest known cohort (351) of infant and young SD decedents, using massively parallel sequencing at less than $600 per sample.
Each year in the United States, thousands of cases of sudden and unexpected deaths of infants, children, and young adults are assigned an undetermined cause of death after postmortem investigation and autopsy. Heritable genetic variants have been suggested as the cause of up to a third of SD cases. Elucidation of the genetic variants involved in SD cases is important to not only help establish cause and manner of death of these individuals, but to also aid in determining whether familial genetic testing should be considered. Previously, these types of postmortem screenings have not been a feasible option for most county medical examiners' and coroners' offices. In the current study, genetic variants were assessed through literature review and clinical evaluation by a multidisciplinary consortium of experts. Thirteen individuals (3.7 percent), eight infants (2.8 percent of those less than 1 year old) and five children/young adults (7.0 percent of those older than 1 year old) were found to have a reportable genetic variant contributing to SD. These percentages represent an estimate lower than those previously reported. The overall conclusion of this study is that yields and results vary between studies likely due to differences in evaluation techniques and reporting. It recommends ongoing assessment of data, including non-reported novel variants, as technology and literature continually advance. This study demonstrates a strategy to implement molecular autopsies in medicolegal investigations of young SD decedents. (Publisher abstract modified)