Sudden unexplained death in the young: epidemiology, aetiology and value of the clinically guided genetic screening

Europace. 2018 Mar 1;20(3):472-480. doi: 10.1093/europace/euw362.

Abstract

Aims: To determine the incidence and the causes of sudden death (SD) in persons aged 1-35 years old and the diagnostic yield of clinically guided genetic screening in the sudden arrhythmic death syndrome (SADS) victims' families.

Methods and results: Incidence and causes of SD in the Attica region of Greece in 2002-10 were determined using death certificates and autopsy reports. We evaluated clinically consecutive families of SADS victims and if a clinical diagnosis was established, we proceeded to targeted genetic analysis. Out of 6030 deaths, 56% were due to traumatic or violent causes, 40.5% were natural deaths, and 3.3% were of undetermined cause. There were 349 SD cases. Cardiovascular causes accounted for 65%, non-cardiovascular causes for 17%, and SADS for 18%. Clinical evaluation identified an inherited heart disease in 5/20 SADS families (25%). Targeted genetic analysis identified a causative mutation in all of the five screened families and reconfirmed the diagnosis in three of five proband victims. Clinical and genetic evaluation of 28 family members identified eight affected carriers and eight non-affected carriers. Molecular autopsy failed to identify any of these families.

Conclusion: Sudden death in the young is of cardiovascular origin in the majority of cases. A considerable rate of SD cases remains of unknown cause on post-mortem. Apart from channelopathies, subclinical forms of inherited structural heart diseases would appear to be implicated in SADS. Clinically guided genetic screening has a significant diagnostic yield and identifies affected families that would have been missed by the current suggested molecular autopsy panel.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Arrhythmias, Cardiac / diagnosis
  • Arrhythmias, Cardiac / genetics*
  • Arrhythmias, Cardiac / mortality*
  • Arrhythmias, Cardiac / physiopathology
  • Autopsy
  • Cause of Death
  • Child
  • Child, Preschool
  • DNA Mutational Analysis*
  • Death, Sudden, Cardiac / epidemiology*
  • Echocardiography
  • Electrocardiography
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genetic Testing / methods*
  • Greece / epidemiology
  • Heredity
  • Humans
  • Incidence
  • Infant
  • Male
  • Mutation*
  • Pedigree
  • Phenotype
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors
  • Young Adult

Substances

  • Genetic Markers