Challenges and opportunities for integrating genetic testing into a diagnostic workflow: heritable long QT syndrome as a model
-
Ira M. Lubin
,
Edward R. Lockhart
Abstract
Background
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.
Content
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.
Acknowledgments
This project was supported in part by an appointment of Edward R Lockhart to the Research Participation Program at the Centers for Disease Control and Prevention (CDC) administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC. We thank Diego Arambula and Danielle Robinson-Holland for their careful review of the manuscript and helpful comments.
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.
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Articles in the same Issue
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- Editorial
- Driving on a highway to hell I found the stairway to heaven. A mentorship lecture intermixed with rock music and a quiz
- Review
- Updated overview on the interplay between obesity and COVID-19
- Mini Review
- Challenges and opportunities for integrating genetic testing into a diagnostic workflow: heritable long QT syndrome as a model
- Opinion Papers
- Making sense of rapid antigen testing in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics
- Interpreting clinical and laboratory tests: importance and implications of context
- Predicting mortality with cardiac troponins: recent insights from meta-analyses
- Guidelines and Recommendations
- Operational measurement of diagnostic safety: state of the science
- Original Articles
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- Assessing the utility of a differential diagnostic generator in UK general practice: a feasibility study
- Assessing physical examination skills using direct observation and volunteer patients
- Clinicians’ and laboratory medicine specialists’ views on laboratory demand management: a survey in nine European countries
- Letters to the Editor
- Frequency of repetitive laboratory testing in patients transferred from the Emergency Department to hospital wards: a 3-month observational study
- Letter in response to Vanstone paper on diagnostic intuition
- Corrigenda
- Corrigendum to: Serious misdiagnosis-related harms in malpractice claims: The “Big Three” – vascular events, infections, and cancers
- Clinical problem solving and social determinants of health: a descriptive study using unannounced standardized patients to directly observe how resident physicians respond to social determinants of health
- Acknowledgment
- Acknowledgment
Articles in the same Issue
- Frontmatter
- Editorial
- Driving on a highway to hell I found the stairway to heaven. A mentorship lecture intermixed with rock music and a quiz
- Review
- Updated overview on the interplay between obesity and COVID-19
- Mini Review
- Challenges and opportunities for integrating genetic testing into a diagnostic workflow: heritable long QT syndrome as a model
- Opinion Papers
- Making sense of rapid antigen testing in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics
- Interpreting clinical and laboratory tests: importance and implications of context
- Predicting mortality with cardiac troponins: recent insights from meta-analyses
- Guidelines and Recommendations
- Operational measurement of diagnostic safety: state of the science
- Original Articles
- Rate of diagnostic errors and serious misdiagnosis-related harms for major vascular events, infections, and cancers: toward a national incidence estimate using the “Big Three”
- Pyoderma gangrenosum underrepresentation in non-dermatological literature
- Assessing the utility of a differential diagnostic generator in UK general practice: a feasibility study
- Assessing physical examination skills using direct observation and volunteer patients
- Clinicians’ and laboratory medicine specialists’ views on laboratory demand management: a survey in nine European countries
- Letters to the Editor
- Frequency of repetitive laboratory testing in patients transferred from the Emergency Department to hospital wards: a 3-month observational study
- Letter in response to Vanstone paper on diagnostic intuition
- Corrigenda
- Corrigendum to: Serious misdiagnosis-related harms in malpractice claims: The “Big Three” – vascular events, infections, and cancers
- Clinical problem solving and social determinants of health: a descriptive study using unannounced standardized patients to directly observe how resident physicians respond to social determinants of health
- Acknowledgment
- Acknowledgment
