Yield of genetic screening in inherited cardiac channelopathies: how to prioritize access to genetic testing

Circ Arrhythm Electrophysiol. 2009 Feb;2(1):6-15. doi: 10.1161/CIRCEP.108.782888. Epub 2009 Feb 10.


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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Arrhythmias, Cardiac / diagnosis*
  • Arrhythmias, Cardiac / economics
  • Arrhythmias, Cardiac / genetics*
  • Atrioventricular Block / diagnosis
  • Atrioventricular Block / genetics
  • Brugada Syndrome / diagnosis
  • Brugada Syndrome / genetics
  • Child
  • Cost-Benefit Analysis
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing* / economics
  • Health Care Costs
  • Health Priorities* / economics
  • Health Services Accessibility* / economics
  • Humans
  • Insurance, Health, Reimbursement
  • Ion Channels / genetics*
  • Italy
  • Logistic Models
  • Long QT Syndrome / diagnosis
  • Long QT Syndrome / genetics
  • Male
  • Mass Screening / economics
  • Mass Screening / methods*
  • Muscle Proteins / genetics
  • Mutation
  • NAV1.5 Voltage-Gated Sodium Channel
  • Patient Selection*
  • Phenotype
  • Potassium Channels, Voltage-Gated / genetics
  • Predictive Value of Tests
  • Retrospective Studies
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Sodium Channels / genetics
  • Tachycardia, Ventricular / diagnosis
  • Tachycardia, Ventricular / genetics
  • Young Adult


  • Ion Channels
  • Muscle Proteins
  • NAV1.5 Voltage-Gated Sodium Channel
  • Potassium Channels, Voltage-Gated
  • Ryanodine Receptor Calcium Release Channel
  • SCN5A protein, human
  • Sodium Channels