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Genetics of Epilepsy in the Era of Precision Medicine: Implications for Testing, Treatment, and Genetic Counseling

Abstract

Purpose of Review

Epilepsy is among the most common neurological diseases, affecting 65 million people worldwide. Recent revisions to the classification of epilepsies by the International League Against Epilepsy (ILAE) reflect a growing awareness of genetic contributions to epilepsy. Research in epilepsy genetics has begun to look beyond gene discovery to the horizon of genotype-driven precision medicine.

Recent Findings

During the past 5 years, the advent of next-generation sequencing has led to exponential growth in the discovery of epilepsy-related genes. The yield of clinically available genetic tests for patients with epilepsy may be as high as 50%, particularly among patients with early-onset epileptic encephalopathy (EOEE). Among patients with early-life epilepsies who have a genetic diagnosis, de novo pathogenic variants are most frequently observed, and rates of somatic mosaicism among both patients and parents are higher than initially anticipated. Phenotypic heterogeneity is quite broad for many epilepsy-related genes, and genotype-phenotype correlations continue to prove complex and at times challenging.

Summary

With a focus on early-life epilepsies, we review recent highlights from the literature regarding gene discovery, approaches to and outcomes of clinical genetic evaluation, and contemporary efforts toward precision treatment. We also address genetic counseling issues of relevance for this population.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Acknowledgments

The authors wish to thank Ann Poduri, MD, MPH, for her critical feedback on this manuscript.

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Correspondence to Beth Rosen Sheidley.

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Katherine L. Helbig reports personal fees from Ambry Genetics, outside of the submitted work. The other authors declare that they have no conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Genetic Counseling and Clinical Testing

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Sheidley, B.R., Smith, L.A. & Helbig, K.L. Genetics of Epilepsy in the Era of Precision Medicine: Implications for Testing, Treatment, and Genetic Counseling. Curr Genet Med Rep 6, 73–82 (2018). https://doi.org/10.1007/s40142-018-0139-8

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  • DOI: https://doi.org/10.1007/s40142-018-0139-8

Keywords

  • Epilepsy
  • Genetics
  • Genetic counseling
  • Genetic testing
  • EOEE
  • Precision medicine