Current practice in diagnostic genetic testing of the epilepsies

Abstract

Epilepsy genetics is a rapidly developing field, in which novel disease-associated genes, novel mechanisms associated with epilepsy, and precision medicine approaches are continuously being identified. In the past decade, advances in genomic knowledge and analysis platforms have begun to make clinical genetic testing accessible for, in principle, people of all ages with epilepsy. For this reason, the Genetics Commission of the International League Against Epilepsy (ILAE) presents this update on clinical genetic testing practice, including current techniques, indications, yield of genetic testing, recommendations for pre-and post-test counseling, and follow-up after genetic testing is completed. We acknowledge that the resources vary across different settings but highlight that genetic diagnostic testing for epilepsy should be prioritized when the likelihood of an informative finding is high. Results of genetic testing, in particular the identification of causative genetic variants, are likely to improve individual care. We emphasize the importance of genetic testing for individuals with epilepsy as we enter the era of precision therapy.

Genetic diagnostics in epilepsies: recommendations of the Commission Epilepsy and Genetics of German Society of Epileptology (German ILAE Chapter)

“…Blaue Linien zeigen in Abhängigkeit individueller Umstände mögliche zusätzliche Szenarien auf. Erstellt mit BioRender.com, adaptiert von Krey et al [1] ten die jeweiligen Labore aktiv kontaktiert werden.…”

“…Die Kommission gibt regelmäßig überarbeitete Empfehlungen heraus und organisiert zudem Symposien zu klinisch relevanten Aspekten der Genetik auf den Jahrestagungen der DG-fE. Diese aktuell vorliegenden Empfehlungen stellen eine Weiterentwicklung der letzten Version von Dezember 2021 dar und tragen den aktuellen Empfehlungen der International League Against Epilepsie (ILAE) Commission on Genetics Rechnung [1]. Aufgrund der schnellen und umfangreichen Änderungen in dem Feld der Epilepsiegenetik kann diese Übersicht keineswegs vollständig sein.…”

“…CMA Array-Analyse, ES Exomsequenzierung, RP-PCR repeat-primed polymerase chain reaction, PME Progressive Myoklonusepilepsie, MCD Fehlbildungen der kortikalen Entwicklung (malformations of cortical development). Adaptiert von Krey et al[1] Exom-oder Genomsequenzierung wird empfohlen, abhängig von Verfügbarkeit und lokalen Standards. Wenn beides nicht verfügbar sein sollte, kann eine Panel-Sequenzierung aller krankheitsrelevanten Gene erwogen werden…”

Focal epilepsies: Update on diagnosis and classification

“…Genetic etiologies in focal epilepsy are increasingly being diagnosed and this will eventually drive management from an empirical approach to that of precision medicine. 28,29 However, genetic testing is not yet routinely integrated in the evaluation of adults with epilepsy. Over the past two decades, numerous genetic variants associated with various epilepsies have been identified.…”

Cytogenomic epileptology

“…Clinical and diagnostic practice (including genetic testing) in epileptology is performed using the classification. Genetic classification of epilepsy, which is less official than clinical and is closer to nature, is almost completely dedicated to monogenic forms/syndromes [ 95 ]. Thus, 977 epilepsy-associated genes were classified according to the clinical outcomes of the mutations/variants.…”