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Genetik epileptischer Enzephalopathien

Genetic epileptic encephalopathies

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Zusammenfassung

Epileptische Enzephalopathien sind definiert als Krankheitsverläufe, bei denen die epileptische Aktivität in Form von Anfällen oder EEG-Auffälligkeiten zu zunehmenden Funktionsstörungen des Gehirns führt. Häufig, aber nicht ausschließlich, handelt es sich dabei um früh beginnende und schwer behandelbare Epilepsien. Dazu gehören definierte elektroklinische Syndrome wie z. B. das West-Syndrom oder das Lennox-Gastaut-Syndrom. Im klinischen Alltag ist jedoch eine eindeutige Zuordnung zu den spezifischen Syndromen in vielen Fällen nicht möglich. Diese „nichtklassischen“ epileptischen Enzephalopathien zeigen neben Überschneidungen zu den klassischen Syndromen auch distinkte Charakteristika. Neben strukturellen und metabolischen Ursachen konnten in den letzten Jahren zahlreiche neue Genveränderungen in Zusammenhang mit epileptischen Enzephalopathien nachgewiesen werden. Hierbei wird zunehmend die genetische Heterogenität dieser Erkrankungsgruppe deutlich. Es werden aber auch funktionelle Gemeinsamkeiten der ursächlichen Gene erkennbar. So verursachen verschiedene Gene gleichartige Krankheitsbilder und im Gegenzug können Veränderungen im gleichen Gen sehr unterschiedliche Phänotypen bedingen. Um dieser Tatsache auch im klinischen Alltag gerecht zu werden, bietet insbesondere die Gen-Panel-Diagnostik eine effektive und schnelle diagnostische Methode.

Die Bedeutung der Sicherung der genetischen Diagnose liegt nicht nur in der Ersparnis weiterer, möglicherweise belastender Diagnostik. Sie dient auch der genetischen und prognostischen Beratung und eröffnet zudem zunehmend spezifische Therapieoptionen.

In dieser Übersichtsarbeit werden die wesentlichen epileptischen Enzephalopathien mit entsprechenden genetischen Veränderungen dargestellt.

Abstract

Epileptic encephalopathies are characterized by early seizure onset or EEG abnormalities, leading to increasing brain dysfunction. They often consist of early-onset and pharmacoresistant epilepsies, including well-defined electro-clinical syndromes such as West syndrome or Lennox–Gastaut syndrome. In many cases of clinical routine, assignment to one of these defined syndromes is not possible. These cases of “non-classical” epileptic encephalopathy often show a certain overlap with the classical syndromes, but display additional distinct features. In addition to structural and metabolic causes, over the last few years numerous new genetic mutations have constituted the main etiology of this disease group. Knowledge about the genetic heterogeneity of this disease group has thereby grown exponentially, revealing the functional similarities of the causative genes. Different genes may cause similar conditions and, vice versa, mutations of the same gene may lead to widely differing phenotypes. To deal with this steadily growing complexity in clinical routine, gene panel analysis in particular provides a fast and efficient method.

The establishment of a genetic diagnosis can prevent ongoing, possibly harmful or distressing diagnostic tests, allows genetic and prognostic counseling, and increasingly offers opportunities for targeted treatment.

This review provides an overview of the main epileptic encephalopathies and the corresponding genetic mutations.

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Authors and Affiliations

  1. Abteilung Neurologie mit Schwerpunkt Epileptologie, Zentrum für Neurologie, Hertie-Institut für Klinische Hirnforschung, Universität Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Deutschland

    Stefan Wolking &  Yvonne G. Weber

  2. Norddeutsches Epilepsiezentrum für Kinder und Jugendliche, Schwentinental-Raisdorf und Klinik für Neuropädiatrie, Arbeitsgruppe Pädiatrische Epilepsiegenetik, Universität Kiel, Kiel, Deutschland

    Sarah von Spiczak

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  1. Stefan Wolking
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Correspondence to Yvonne G. Weber.

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S. Wolking, S. von Spiczak und Y. G. Weber geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Wolking, S., von Spiczak, S. & Weber, Y.G. Genetik epileptischer Enzephalopathien. Z. Epileptol. 29, 70–76 (2016). https://doi.org/10.1007/s10309-015-0034-1

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  • DOI: https://doi.org/10.1007/s10309-015-0034-1

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