Sudden arrhythmic death syndrome: familial evaluation identifies inheritable heart disease in the majority of families

Eur Heart J. 2008 Jul;29(13):1670-80. doi: 10.1093/eurheartj/ehn219. Epub 2008 May 27.


Aims: At least 4% of sudden deaths are unexplained at autopsy [sudden arrhythmic death syndrome (SADS)] and a quarter may be due to inherited cardiac disease. We hypothesized that comprehensive clinical investigation of SADS families would identify more susceptible individuals and causes of death.

Methods and results: Fifty seven consecutively referred families with SADS death underwent evaluation including resting 12 lead, 24 h and exercise ECG and 2D echocardiography. Other investigations included signal averaged ECG, ajmaline testing, cardiac magnetic resonance imaging, and mutation analysis. First-degree relatives [184/262 (70%)] underwent evaluation, 13 (7%) reporting unexplained syncope. Seventeen (30%) families had a history of additional unexplained premature sudden death(s). Thirty families (53%) were diagnosed with inheritable heart disease: 13 definite long QT syndrome (LQTS), three possible/probable LQTS, five Brugada syndrome, five arrhythmogenic right ventricular cardiomyopathy (ARVC), and four other cardiomyopathies. One SCN5A and four KCNH2 mutations (38%) were identified in 13 definite LQTS families, one SCN5A mutation (20%) in five Brugada syndrome families and one (25%) PKP2 (plakophyllin2) mutation in four ARVC families.

Conclusion: Over half of SADS deaths were likely to be due to inherited heart disease; accurate identification is vital for appropriate prophylaxis amongst relatives who should undergo comprehensive cardiological evaluation, guided and confirmed by mutation analysis.

MeSH terms

  • Adult
  • Algorithms
  • Arrhythmias, Cardiac / genetics*
  • Cardiomyopathies / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Death, Sudden, Cardiac / etiology*
  • Female
  • Genetic Testing
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Pedigree