title: Low rate of cardiac events in first-degree relatives of diagnosis-negative young sudden unexplained death syndrome victims during follow-up.
abstract: BACKGROUND
  Sudden unexplained death syndrome (SUDS) in young individuals often results from inherited cardiac disease. Accordingly, comprehensive examination in surviving first-degree relatives unmasks such disease in approximately 35% of the families. It is unknown whether individuals from diagnosis-negative families are at risk of developing manifest disease or cardiac events during follow-up.
  
  
  OBJECTIVE
  This study aimed to study the prognosis of first-degree relatives of young SUDS victims, in whom the initial cardiologic and genetic examination did not lead to a diagnosis.
  
  
  METHODS
  We retrieved vital status of surviving first-degree relatives from 83 diagnosis-negative families who presented to our cardiogenetics department between 1996 and 2009 because of SUDS in ≥1 relatives aged 1-50 years. Moreover, we contacted relatives who previously visited our center for detailed information.
  
  
  RESULTS
  We obtained detailed information (median follow-up 6.6 years; interquartile range 4.7-9.6 years) in 340 of 417 first-degree relatives (81.5%) from 77 of 83 families (92.8%). Vital status, available in 405 relatives (97.1%), showed that 20 relatives (4.9%) died during follow-up, including 1 natural death before the age of 50. This girl belonged to a family with multiple cases of idiopathic ventricular fibrillation and SUDS, including another successfully resuscitated sibling during follow-up. Two hundred thirty-four of 340 first-degree relatives (68.8%) underwent cardiologic examination. Of these, 76 (32.5%) were reevaluated. Inherited cardiac disease was diagnosed in 3 families (3.6%).
  
  
  CONCLUSIONS
  In first-degree relatives of young SUDS victims with no manifest abnormalities during the initial examination, the risk of developing manifest inherited cardiac disease or cardiac events during follow-up is low. This does not apply to families with obvious familial SUDS.
authors.affiliation: Heart Center, Department of Cardiology. Electronic address: C.vanderwerf@amc.uva.nl.
authors.forename: Christian
authors.initials: C
authors.lastname: van der Werf
authors.affiliation: Heart Center, Department of Cardiology.
authors.forename: Lotte
authors.initials: L
authors.lastname: Stiekema
authors.affiliation: Heart Center, Department of Cardiology.
authors.forename: Hanno L
authors.initials: HL
authors.lastname: Tan
authors.affiliation: Department of Clinical Genetics.
authors.forename: Nynke
authors.initials: N
authors.lastname: Hofman
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marielle
authors.initials: M
authors.lastname: Alders
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
authors.affiliation: Department of Genetics, University Medical Center, University of Groningen, Groningen, The Netherlands.
authors.forename: Irene M
authors.initials: IM
authors.lastname: van Langen
authors.affiliation: Heart Center, Department of Cardiology; Princess Al-Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
mesh_terms: D000293:Adolescent; D000328:Adult; D053840:Brugada Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D010375:Pedigree; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D055815:Young Adult
keywords: Arrhythmia; Genetics; Sudden cardiac death; Sudden unexplained death syndrome