Genetic Screening for Brugada and Long QT Syndromes Is of No Value

Summary and Comment |
January 21, 2016

Genetic Screening for Brugada and Long QT Syndromes Is of No Value

  1. Mark S. Link, MD

In an unselected population, genetic screening was inaccurate and did not find clinical disease.

  1. Mark S. Link, MD

Many people hope that genetic screening will allow for the early diagnosis and thus treatment of diseases, and it seems intuitive that genetic syndromes would be easily diagnosed with population screening. The current researchers examined the effectiveness of screening in an unselected population for variant alleles associated with two of the more common genetic syndromes in cardiology, long QT syndrome (LQTS) and Brugada syndrome.

Participants were drawn from a cohort of patients recruited for nonantiarrhythmic drug exposure. Testing of SCN5A and KCNH2 was performed by one academic and two commercial laboratories, without knowledge of clinical phenotypes. Results were correlated with electronic medical records (median follow-up, 18 years), including electrocardiography in 1270 patients.

Of 2022 individuals screened for SCN5A and KCNH2, there were 63 individuals with 42 rare, possibly pathogenic, allelic variants found by at least one laboratory. Correlation between the laboratories was quite poor (Cohen κ=0.26). A clinical diagnosis of LQTS or Brugada based on ICD-9 codes for either syndrome was no more likely in those with a variant allele (11/63; 17%) than in those without (264/1959; 13%). Median QTc also did not differ between carriers and noncarriers (429 and 439 milliseconds).

Comment

The current study demonstrates the current limitations of genetic screening in a general population. The poor concordance among laboratories is concerning, as is the finding that individuals with a variant allele were no more likely to have the phenotype than those without. The authors contend that these results argue against patient notification of unexpected and incidental findings on genetic testing. However, supporters of genetic screening of athletes and children and enthusiasts of personalized medicine should also take note. Genetic screening is not warranted for individuals without a suspected diagnosis of a disease. Editorialists also call for caution when interpreting pathologic genetic information.

Editor Disclosures at Time of Publication

  • Disclosures for Mark S. Link, MD at time of publication Grant / Research support Unequal Technologies Editorial boards UpToDate; Heart Rhythm Leadership positions in professional societies Heart Rhythm Society (Chair, CME Compliance Committee); American Heart Association (Chair, ACLS Writing Group; Member, Emergency Cardiovascular Care)

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