title: Contribution of inherited heart disease to sudden cardiac death in childhood.
abstract: BACKGROUND
  In children aged 1 to 18 years, the causes of sudden cardiac death may remain unresolved when autopsy results are negative. Because inherited cardiac diseases are likely, cardiologic and genetic investigations of relatives may still yield the diagnosis in these cases. Moreover, these investigations provide timely identification of relatives who are also at risk of sudden cardiac death. We aimed to establish the cause of sudden cardiac death in the children of whom the family was referred to our cardiogenetics department and the diagnostic yield of these investigations.
  
  
  RESULTS
  We genetically counseled 25 consecutive, unrelated families after sudden cardiac death of a child (aged 1 to 18 years) who was disease-free during lifetime and in whose family there was no known inherited heart disease. We performed cardiac investigation (electrocardiography, exercise testing, and echocardiography) of first-degree and second-degree relatives and performed diagnosis-directed DNA analysis. Autopsy was performed in 20 case subjects. A diagnosis was identified in 14 of 25 families. In addition, we studied 10 children after aborted sudden cardiac death; in 6 of them, a diagnosis was made. Overall, in 17 of the 19 families in whom an inherited disease was diagnosed, a disease-causing mutation in either a first-degree relative or the index patient confirmed the diagnosis.
  
  
  CONCLUSIONS
  Sudden cardiac death in children seems to be caused often by inherited cardiac diseases. Cardiac and genetic examination of relatives combined, if possible, with postmortem analysis after sudden cardiac death of a child has a high diagnostic yield (14 of 25), comparable to analysis in surviving victims of sudden cardiac death (6 of 10). Because sudden cardiac death can be prevented by timely treatment, these results warrant active family screening after unexplained sudden cardiac death of a child.
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Nynke
authors.initials: N
authors.lastname: Hofman
authors.forename: Hanno L
authors.initials: HL
authors.lastname: Tan
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Clur
authors.forename: Mariel
authors.initials: M
authors.lastname: Alders
authors.forename: Irene M
authors.initials: IM
authors.lastname: van Langen
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
mesh_terms: D000293:Adolescent; D000465:Algorithms; D016887:Cardiopulmonary Resuscitation; D002648:Child; D004252:DNA Mutational Analysis; D003645:Death, Sudden / Q000209:etiology*; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control; D004452:Echocardiography; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D005817:Genetic Counseling; D005820:Genetic Testing; D006331:Heart Diseases / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree