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Official Journal of the Society to Improve Diagnosis in Medicine (SIDM)

Editor-in-Chief: Graber, Mark L. / Plebani, Mario

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Challenges and opportunities for integrating genetic testing into a diagnostic workflow: heritable long QT syndrome as a model

Ira M. Lubin / Edward R. Lockhart / Julie Frank / Vincent Y. See
  • Cardiovascular Medicine Division and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
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/ Sudhir Vashist
  • Division of Cardiology and Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA
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/ Carol Greene
Published Online: 2019-07-09 | DOI: https://doi.org/10.1515/dx-2019-0018



An increasing number of diagnostic evaluations incorporate genetic testing to facilitate accurate and timely diagnoses. The increasing number and complexity of genetic tests continue to pose challenges in deciding when to test, selecting the correct test(s), and using results to inform medical diagnoses, especially for medical professionals lacking genetic expertise. Careful consideration of a diagnostic workflow can be helpful in understanding the appropriate uses of genetic testing within a broader diagnostic workup.


The diagnosis of long QT syndrome (LQTS), a life-threatening cardiac arrhythmia, provides an example for this approach. Electrocardiography is the preferred means for diagnosing LQTS but can be uninformative for some patients due to the variable presentation of the condition. Family history and genetic testing can augment physiological testing to inform a diagnosis and subsequent therapy. Clinical and laboratory professionals informed by peer- reviewed literature and professional recommendations constructed a generalized LQTS diagnostic workflow. This workflow served to explore decisions regarding the use of genetic testing for diagnosing LQTS.

Summary and outlook

Understanding the complexities and approaches to integrating genetic testing into a broader diagnostic evaluation is anticipated to support appropriate test utilization, optimize diagnostic evaluation, and facilitate a multidisciplinary approach essential for achieving accurate and timely diagnoses.

Keywords: arrhythmias; diagnosis; genetic testing; long QT syndrome


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About the article

Corresponding author: Ira M. Lubin, PhD, FACMG, Division of Laboratory Systems, Centers for Disease Control and Prevention, 1600 Clifton Rd., MS V24-3, Atlanta, GA 30329, USA

Received: 2019-03-04

Accepted: 2019-06-18

Published Online: 2019-07-09

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: VYS received support from the American Heart Association, Funder Id: http://dx.doi.org/10.13039/100000968: Award Number 16MCPRP31350041.

Employment: IML is employed by the Centers for Disease Control and Prevention. JF, VYS, and CF are employed by the University of Maryland School of Medicine.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC or the US Agency for Toxic Substances and Disease Registry.

Citation Information: Diagnosis, 20190018, ISSN (Online) 2194-802X, ISSN (Print) 2194-8011, DOI: https://doi.org/10.1515/dx-2019-0018.

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