Surviving Sudden Death: Where Does Next-Generation Sequencing Fit in the Assessment of Sudden Death Victims and Their Families.

Abstract

The investigation of sudden death is one of the few enduring responsibilities of the coronial system that had its origins in 11th century Britain and was formally established by the articles of Eyre in 1194.1 People finding a body from a sudden or unnatural death were required to raise a hue and cry and notify the coroner. See Article by Lin et al Although the familial nature of sudden death, including structural and electric cardiomyopathies, has been recognized for many decades, British pathologist MJ Davies2 in 1999 may have been the first to suggest that the family might be approached in the evaluation of sudden cardiac death (SCD). In the same year, Ackerman et al3 used molecular diagnosis to identify the cause of SCD in a 19-year-old who died after near-drowning, heralding the era of what would be called the molecular autopsy. (Of note, the decedent’s mother had a definitely prolonged QT interval) Shortly thereafter, clinical genetic testing for inherited arrhythmia conditions became increasingly available. Potential approaches to identifying heritable causes of SCD include family assessment, molecular assessment, or a combined approach (see Table). View this table: Table 1. Selected studies of clinical and/or genetic assessment of sudden cardiac death or arrest victims and their families Behr et al4 clinically evaluated 147 first-degree relatives of 32 sudden arrhythmia death syndrome victims with a 22% diagnostic yield for the cause of SCD, whereas more recently, in a larger cohort of victims, …