title: Mortality of inherited arrhythmia syndromes: insight into their natural history.
abstract: BACKGROUND
  For most arrhythmia syndromes, the risk of sudden cardiac death for asymptomatic mutation carriers is ill defined. Data on the natural history of these diseases, therefore, are essential. The family tree mortality ratio method offers the unique possibility to study the natural history at a time when the disease was not known and patients received no treatment.
  
  
  RESULTS
  In 6 inherited arrhythmia syndromes caused by specific mutations, we analyzed all-cause mortality with the family tree mortality ratio method (main outcome measure, standardized mortality ratio [SMR]). In long-QT syndrome (LQTS) type 1, severely increased mortality risk during all years of childhood was observed (1-19 years), in particular during the first 10 years of life (SMR, 2.9; 95% CI, 1.5-5.1). In LQTS type 2, we observed increasing SMRs starting from age 15 years, which just reached significance between age 30 and 39 (SMR, 4.0; 95% CI, 1.1-10.0). In LQTS type 3, the SMR was increased between age 15 and 19 years (SMR, 5.8; 95% CI, 1.2-16.9). In the SCN5A overlap syndrome, excess mortality was observed between age 10 and 59 years, with a peak between 20 and 39 years (SMR, 3.8; 95% CI, 2.5-5.7). In catecholaminergic polymorphic ventricular tachycardia, excess mortality was restricted to ages 20 to 39 years (SMR, 3.0; 95% CI, 1.3-6.0). In Brugada syndrome, excess mortality was observed between age 40 and 59 (SMR, 1.79; 95% CI, 1.2-2.4), particularly in men.
  
  
  CONCLUSIONS
  We identified age ranges during which the mortality risk manifests in an unselected and untreated population, which can guide screening in these families.
authors.affiliation: Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands. e.a.nannenberg@amc.uva.nl
authors.forename: Eline A
authors.initials: EA
authors.lastname: Nannenberg
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.forename: Lea M
authors.initials: LM
authors.lastname: Dijksman
authors.forename: Marielle
authors.initials: M
authors.lastname: Alders
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
authors.forename: Martijn
authors.initials: M
authors.lastname: Birnie
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; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008133:Long QT Syndrome / Q000151:congenital / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult