Abstract
The contribution of genetics to both rare and common epilepsies is rapidly being elucidated, and neurologists are routinely considering genetic testing in the work-up of several epilepsy syndromes of both known and unknown cause. Simultaneously, advances in molecular technology foreshadow additional discoveries in epilepsy etiology, implying a greater role than ever before for genetics in the epilepsy clinic. Genetic testing can be valuable not only for diagnosis but also for guiding treatment and for informing reproductive choices. In this Review, we outline the principles of genetic evaluation and counseling, and describe how to interpret genetic test results for epilepsy in the following five common clinical scenarios: Dravet syndrome, infantile spasms, epilepsy with cortical malformation, epilepsy with mental retardation, and idiopathic epilepsy syndromes. We differentiate clinical situations in which genetic testing is of high and low utility, and predict future areas for the application of genetics in epilepsy practice.
Key Points
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In certain defined epilepsy syndromes, genetic tests that include chromosome microarray analysis and sequencing-based tests have clinical utility and can help to guide clinical management and accurately predict recurrence risk
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The genetic tests currently offered for common epilepsies are of limited validity or utility, as well as being potentially wasteful of time and resources, and confusing to clinicians
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Development of clinically useful diagnostic tests for common epilepsies is challenging, as such applications will have to account for genetic heterogeneity and to correlate with meaningful aspects of the epilepsy phenotype
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The principles of genetic evaluation still rest on clinical foundations, with the emphasis placed on the identification of patients with specific epilepsy syndromes through clinical investigation
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In the future, genetic variants that predict prognosis, comorbidities and drug response might fulfill the vaunted promise of personalized medicine
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Acknowledgements
This manuscript was supported by members of the Partnership for Pediatric Epilepsy Research (including the American Epilepsy Society, the Epilepsy Foundation, A. Fantaci and J. Fantaci, Fight Against Childhood Epilepsy and Seizures, Neurotherapy Ventures Charitable Research Fund, and Parents Against Childhood Epilepsy), the Epilepsy Foundation (through the generous support of the Charles L. Shor Foundation for Epilepsy Research), People Against Childhood Epilepsy, Ali Paris Fund and the NIH (grant NS047530 to D. K. Pal). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke, NIH, or any other sponsor. We thank the anonymous reviewers for their comments.
Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.
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D. K. Pal has patent applications with Columbia University Medical Center for BRD2 and ELP4 variants, while W. K. Chung acts as a consultant for Bio-Reference Laboratories. A. W. Pong declares no competing interests.
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Pal, D., Pong, A. & Chung, W. Genetic evaluation and counseling for epilepsy. Nat Rev Neurol 6, 445–453 (2010). https://doi.org/10.1038/nrneurol.2010.92
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DOI: https://doi.org/10.1038/nrneurol.2010.92
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