title: A large family characterised by nocturnal sudden death.
abstract: BACKGROUND
  We recently identified a novel mutation in large family characterised by premature nocturnal sudden death. In the present paper we provide an overview of the findings in this family.
  
  
  METHODS
  From 1958 onwards, when the first patient presented, we collected clinical data on as many family members as possible. After identification in 1998 of the underlying genetic disorder (SCN5A, 1795insD), genotyping was performed diagnostically.
  
  
  RESULTS
  Since 1905 unexplained sudden death occurred in 26 family members, 17 of whom died during the night. Besides sudden death, symptomatology was rather limited; only six patients reported syncopal attacks. In one of them, a 13-year-old boy, asystolic episodes up to nine seconds were documented. Until now, the mutation has been found in 114 family members (57 males, 57 females). Carriers of the mutant gene exhibited bradycardia-dependent QT-prolongation, intrinsic sinus node dysfunction, generalised conduction abnormalities, a paucity of ventricular ectopy, and the Brugada sign. Cardiomyopathy or other structural abnormalities were not found in any of the carriers. Electrophysiological studies showed that mutant channels were characterised by markedly reduced INaamplitude, a positive shift of voltage-dependence of activation and a substantial negative shift of voltage-dependence of inactivation of INa. From 1978 onwards, a pacemaker for anti-brady pacing was implanted for prevention of sudden death. In patients in whom a prophylactic pacemaker was implanted no unexplained sudden death occurred, whereas 5 sudden deaths occurred in the group of patients who did not receive a pacemaker.
  
  
  CONCLUSIONS
  We have described a large family with a SCN5A-linked disorder (1795insD) with features of LQT3, Brugada syndrome and familial conduction system disease. Anti-brady pacing was successful in preventing sudden death. The mode of death is possibly bradycardic.
authors.forename: M P
authors.initials: MP
authors.lastname: van den Berg
authors.forename: J W
authors.initials: JW
authors.lastname: Viersma
authors.forename: G C M
authors.initials: GC
authors.lastname: Beaufort-Krol
authors.forename: M Th E
authors.initials: MT
authors.lastname: Bink-Boelkens
authors.forename: C R
authors.initials: CR
authors.lastname: Bezzina
authors.forename: M W
authors.initials: MW
authors.lastname: Veldkamp
authors.forename: J
authors.initials: J
authors.lastname: Brouwer
authors.forename: J
authors.initials: J
authors.lastname: Haaksma
authors.forename: J P
authors.initials: JP
authors.lastname: van Tintelen
authors.forename: I M
authors.initials: IM
authors.lastname: van Langen
authors.forename: A A
authors.initials: AA
authors.lastname: Wouda
authors.forename: A A M
authors.initials: AA
authors.lastname: Wilde
keywords: Brugada syndrome; SCN5A; long-QT syndrome; pacemaker; sudden death