Genomic sequencing in severe epilepsy: a step closer to precision medicine

Abstract

ABSTRACT Introduction: The large number of different syndromes and seizure types, together with an inter-individual variable response to antiepileptic drugs (AEDs), makes the treatment of epilepsy challenging. Areas covered: Early infantile Epileptic encephalopathies (EIEE) are a group of neurodevelopmental disorders consisting of early-onset refractory seizures often accompanied by important developmental delay or regression. The last two decades have seen major advancement in the diagnosis of epilepsy thanks both to modern neuroimaging but, primarily, to new methods in molecular genetics and gene sequencing. The application of Next-Generation Sequencing (NGS) techniques has already helped to understand the genetic diversity and underlying pathogenic mechanisms in severe epilepsy of childhood. Furthermore, the use of Whole Exome Sequencing (WES) in parent–offspring trios has also helped to identify de novo mutations in patients with EIEE. Tailored treatments are already applicable in some monogenic epilepsy, but these are a minority of cases. Expert commentary: In our opinion, the future of epilepsy treatment will be multidisciplinary and possibly very different from the currently almost empiric approach and we are confident that a ‘precision medicine’ will be applicable on large scale.