title: Yield of genetic screening in inherited cardiac channelopathies: how to prioritize access to genetic testing.
abstract: BACKGROUND
  Identification of mutations in cardiac ion channel genes concurs to the diagnosis of long-QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. However, because availability of genetic screening is still limited and reimbursement policies are lacking, there is a need of evidence-based criteria to prioritize access to genetic testing for these diseases.
  
  
  RESULTS
  We determined the yield of genetic testing and cost per positive genotyping in 1394 consecutive probands. Among the 546 patients referred for long-QT syndrome-genes screening, those with clinical diagnosis of long-QT syndrome had the highest yield (64%) and lowest cost (US $8418) for each positive genotyping. Among 798 individuals screened for mutation on the SCN5A gene, the highest yield was obtained in patients with type 1 Brugada syndrome ECG pattern (51 of 405; 13%) corresponding to a cost of US $21441 per positive genotyping. In conclusive Brugada syndrome patients the presence of atrioventricular block (odds ratio: 3.3, CI: 1.8 to 6.1; P=0.0001) increases the yield (23%) of genotyping and reduces its cost (US $ 11700). Among 175 patients screened on RyR2 gene, those with documented bidirectional ventricular tachycardia had the highest incidence (62%) of mutations and the lowest cost (US $5263) per positive genotyping. Genetic screening of unselected family members of sudden cardiac death victims and idiopathic ventricular fibrillation survivors is largely ineffective (yield of 9%) and costly (US $71430 per 1 positive genotyping).
  
  
  CONCLUSIONS
  Genotyping can be performed at reasonable cost in individuals with conclusive diagnosis of long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia, and in patients with type I Brugada syndrome ECG with atrioventricular block. These patients should be given priority to access genetic testing.
authors.affiliation: Molecular Cardiology, IRCCS Fondazione Salvatore Maugeri, Pavia, Italy.
authors.forename: Rong
authors.initials: R
authors.lastname: Bai
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bloise
authors.forename: Nicola
authors.initials: N
authors.lastname: Monteforte
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
mesh_terms: D000293:Adolescent; D000328:Adult; D001145:Arrhythmias, Cardiac / Q000175:diagnosis* / Q000191:economics / Q000235:genetics*; D054537:Atrioventricular Block / Q000175:diagnosis / Q000235:genetics; D053840:Brugada Syndrome / Q000175:diagnosis / Q000235:genetics; D002648:Child; D003362:Cost-Benefit Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000191:economics; D017048:Health Care Costs; D006292:Health Priorities / Q000191:economics; D006297:Health Services Accessibility / Q000191:economics; D006801:Humans; D007349:Insurance, Health, Reimbursement; D007473:Ion Channels / Q000235:genetics*; D007558:Italy; D016015:Logistic Models; D008133:Long QT Syndrome / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008403:Mass Screening / Q000191:economics / Q000379:methods*; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018579:Patient Selection; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult
chemical_list: D007473:Ion Channels; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024642:Potassium Channels, Voltage-Gated; D019837:Ryanodine Receptor Calcium Release Channel; C568320:SCN5A protein, human; D015222:Sodium Channels