title: Clinical heterogeneity in sodium channelopathies. What is the meaning of carrying a genetic mutation?
abstract: BACKGROUND
  Mutations in the SCN5A gene have been linked to a variety of diseases causing sudden cardiac death, with important variability in expressivity and phenotypic overlap. With the availability of genetic testing family members may now be diagnosed as carriers based solely on the presence of the genetic defect. Clinical decision making in this situation is complex and generates important ethical and medicolegal issues.
  
  
  METHODS
  We describe two families, 24-328 and 24-588, originally diagnosed with Brugada syndrome after the probands experienced cardiac arrest and we performed clinical and genetic analysis in their members.
  
  
  RESULTS
  Both families had members with various electrocardiographic abnormalities including some with Brugada syndrome, long QT syndrome and conduction system disease. Both families had an important family history of sudden cardiac death. Direct sequencing of exons and exon-intron boundaries of the sodium channel gene SCN5A identified mutations in both families.
  
  
  CONCLUSIONS
  These two families illustrate an increasingly common scenario when encountering families with ion channelopathies. Because a defibrillator is the only available therapeutic option at present in Brugada syndrome, physicians will be faced with extremely difficult therapeutic decisions that also have important legal, social and ethical implications, especially in children. These data indicate the need to develop guidelines on how to approach the results of genetic testing, especially in asymptomatic individuals.
authors.affiliation: Catholic University, School of Medicine, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliva
authors.forename: Preben
authors.initials: P
authors.lastname: Bjerregaard
authors.forename: Kui
authors.initials: K
authors.lastname: Hong
authors.forename: Steven
authors.initials: S
authors.lastname: Evans
authors.forename: Kevin
authors.initials: K
authors.lastname: Vernooy
authors.forename: Jorge
authors.initials: J
authors.lastname: McCormack
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.forename: Pedro
authors.initials: P
authors.lastname: Brugada
authors.forename: Vincenzo L
authors.initials: VL
authors.lastname: Pascali
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D053840:Brugada Syndrome / Q000235:genetics*; D002648:Child; D016757:Death, Sudden, Cardiac; D004562:Electrocardiography; D017809:Fatal Outcome; D005260:Female; D016368:Frameshift Mutation; D018740:Genetic Heterogeneity; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics*; D020125:Mutation, Missense; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010375:Pedigree; D017422:Sequence Analysis, DNA; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels