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Fokale genetisch bedingte Epilepsiesyndrome

Neue Erkenntnisse in der Entstehung

Focal genetic epilepsy syndromes

New findings

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Zusammenfassung

In der Aufklärung fokaler genetisch bedingter Epilepsiesyndrome wurden in den letzten drei Jahren große Fortschritte erzielt. So wurden Defekte im DEPDC5-Gen, welches ein Protein codiert, das Bestandteil des GATOR1-Komplexes ist, der wiederum eine wichtige Rolle im mTOR-Signalweg spielt, als Ursache fokaler Epilepsien identifiziert. Interessanterweise wurden DEPDC5-Mutationen sowohl bei Kindern mit Rolando-Epilepsie als auch bei Patienten mit kortikalen Dysplasien gefunden. Bei der autosomal dominanten lateralen Temporallappenepilepsie wurde Reelin als ursächliches Gen in 17,5 % der untersuchten Familien identifiziert. Durch Metaanalyse mehrerer großer genomweiter Assoziationsstudien konnte belegt werden, dass Mutationen im SCN1A-Gen bedeutsam sind für die Entstehung häufiger fokaler und generalisierter Epilepsien. Zudem wurde gezeigt, dass auch Mutationen im SCN3A-Gen selten ursächlich für die Entstehung fokaler Epilepsien sein können. In einer Reihe von Studien, die sich mit den genetischen Ursachen bei typischer und atypischer Rolando-Epilepsie befasst haben, konnte nachgewiesen werden, dass Mutationen in den Genen GRIN2A, RBFOX1, RBFOX3 und DEPDC5 sowie eine bestimmte Copy Number Variation (CNV 16p11.2) bei insgesamt 12 % der Patienten pathogenetisch bedeutsam sind. Einzelne der identifizierten Genprodukte sind pharmakologisch beeinflussbar.

Abstract

In the last three years, significant progress in identifying focal genetic epilepsy syndromes was made. DEPDC5, a member of the GATOR1 complex that interacts with the mTOR complex, is involved in a variety of different focal genetic epilepsy syndromes. Defects in DEPDC5 were found in Rolandic epilepsy, as well as in epilepsies with cortical dysplasia. Reelin is responsible for up to 17.5 % of families with lateral temporal lobe epilepsy. In the joint collectives of a large GWAS meta-analysis, the contribution of SCN1A to common focal and generalized epilepsies was reported. SCN3A could finally be confirmed as a rare cause of focal childhood epilepsy. In a series of papers, genetic contributors of typical and atypical Rolandic epilepsy were documented (GRIN2A, RBFOX1 and 3, DEPDC5). The CNV 16p11.2 were found in about 12 % of the investigated cases. Some of these gene products are pharmacologically targetable.

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Authors and Affiliations

  1. Abteilung Kinderneurologie, Sozialpädiatrie u. Epileptologie, Univ.-Klinikum Gießen/Marburg; Standort Gießen, Feulgenstr. 12, 35389, Gießen, Deutschland

    Bernd A. Neubauer &  Andreas Hahn

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  1. Bernd A. Neubauer
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Correspondence to Bernd A. Neubauer.

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B. A. Neubauer und A. Hahn geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Neubauer, B.A., Hahn, A. Fokale genetisch bedingte Epilepsiesyndrome. Z. Epileptol. 29, 57–62 (2016). https://doi.org/10.1007/s10309-015-0032-3

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