Genetic testing and cascade screening in pediatric long QT syndrome and hypertrophic cardiomyopathy

Heart Rhythm. 2020 Jan;17(1):106-112. doi: 10.1016/j.hrthm.2019.06.015. Epub 2019 Jun 20.


Background: The efficacy of cascade screening for the inherited heart conditions long QT syndrome (LQTS) and hypertrophic cardiomyopathy (HCM) is incompletely characterized.

Objective: The purpose of this study was to examine the use of genetic testing and yield of cascade screening across diverse regions in the United States and to evaluate obstacles to screening in multipayer systems.

Methods: An institutional review board-approved 6 United States pediatric center retrospective chart review of LQTS and HCM patients from 2008-2014 was conducted for (1) genetic test completion and results and (2) family cascade screening acceptance, methods, results, and barriers.

Results: The families of 315 index patients (mean age 9.0 ± 5.8 years) demonstrated a 75% (254) acceptance of cascade screening. The yield of relative screening was 39% (232/601), an average of 0.91 detected per family. Genetic testing was less utilized in HCM index patients and relatives. Screening participation was greater in families of gene-positive index patients (88%) (P <.001) compared to gene-negative patients (53%). Cascade method utilization: Cardiology-only 45%, combined genetic and cardiology 39%, and genetic only 16%. Screening yield by method: combined 57%, genetic-only 29%, and cardiology-only 20%. Family decisions were the leading barriers to cascade screening (26% lack of followthrough and 26% declined), whereas insurance (6%) was the least cited barrier.

Conclusion: Family participation in cascade screening is high, but the greatest barriers are family mediated (declined, lack of followthrough). Positive proband genetic testing led to greater participation. Cardiology-only screening was the most utilized method, but combined cardiology and genetic screening had the highest detection.

Keywords: Cascade screening; Hypertrophic cardiomyopathy; Long QT syndrome; Precision medicine; Sudden death.

Publication types

  • Multicenter Study

MeSH terms

  • Cardiomyopathy, Hypertrophic / diagnosis*
  • Cardiomyopathy, Hypertrophic / genetics
  • Child
  • Female
  • Follow-Up Studies
  • Genetic Testing / methods*
  • Humans
  • Long QT Syndrome / diagnosis*
  • Long QT Syndrome / genetics
  • Male
  • Mass Screening / methods*
  • Pedigree
  • Phenotype
  • Reproducibility of Results
  • Retrospective Studies