Prospective, population-based long QT molecular autopsy study of postmortem negative sudden death in 1 to 40 year olds

Heart Rhythm. 2011 Mar;8(3):412-9. doi: 10.1016/j.hrthm.2010.11.016. Epub 2010 Nov 9.


Background: Retrospective investigation of sudden unexplained death in the young (SUDY) reveals that a high proportion is due to inherited heart disease.

Objective: The purpose of this study was to ascertain the diagnostic value of postmortem long QT (LQT) genetic analysis in a prospective study of SUDY victims 1-40 years old.

Methods: Denaturing high-performance liquid chromatography or direct sequencing of LQT genes 1, 2, 3, 5, and 6 was performed, in a National New Zealand protocol, in SUDY victims aged 1-40 years.

Results: Over 26 months (2006-2008), DNA was stored at autopsy from 52 victims of sudden unexpected death. Further testing revealed a diagnosis in 19 cases (poisoning 4, dilated cardiomyopathy 3, myocarditis 3, other 9). The remaining 33 cases underwent genetic testing (age at death 18 months-40 years, median 25 years). Eighteen (55%) died during sleep or at rest, and 7 (21%) died during light activity. Rare missense variants in LQT genes were found in 5 (15%) cases (confidence interval 3%-27%): T96R in KCNQ1 (11-year-old male), P968L in KCNH2 (32-year-old female), P2006A in SCN5A (34-year-old female), and R67H and R98W in KCNE1 (17- and 38-year-old females, respectively). Evidence of pathogenicity was provided by in vitro evidence (T96R), family phenotype-genotype co-segregation (R98W, P2006A), and/or previous reports (R67H, P968L, P2006A, R98W). Family cardiac investigation was possible in 23 (70%) families and revealed probable cause of death for 5 (15%) other victims (confidence interval 3%-27%).

Conclusion: Most community SUDY occurs at rest or during light activity. A diagnostic rate of 15% supports the transition of LQT genetic autopsy, combined with family investigation, into routine medical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid
  • Death, Sudden, Cardiac / epidemiology*
  • Female
  • Genetic Testing
  • Humans
  • Infant
  • KCNQ1 Potassium Channel / genetics
  • Long QT Syndrome / epidemiology
  • Long QT Syndrome / genetics*
  • Male
  • Mutation, Missense
  • NAV1.5 Voltage-Gated Sodium Channel
  • New Zealand / epidemiology
  • Potassium Channels / genetics*
  • Potassium Channels, Voltage-Gated / genetics
  • Prospective Studies
  • Seroepidemiologic Studies
  • Sodium Channels / genetics*
  • Young Adult


  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • NAV1.5 Voltage-Gated Sodium Channel
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • SCN5A protein, human
  • Sodium Channels