title: Management of genetic epilepsies: From empirical treatment to precision medicine.
abstract: Despite the over 20 antiepileptic drugs (AEDs) now licensed for epilepsy treatment, seizures can be effectively controlled in about ∼70% of patients. Thus, epilepsy treatment is still challenging in about one third of patients and this may lead to a severe medically, physically, and socially disabling condition. However, there is clear evidence of heterogeneity of response to existing AEDs and a significant unmet need for effective intervention. A number of studies have shown that polymorphisms may influence the poor or inadequate therapeutic response as well as the occurrence of adverse effects. In addition, the new frontier of genomic technologies, including chromosome microarrays and next-generation sequencing, improved our understanding of the genetic architecture of epilepsies. Recent findings in some genetic epilepsy syndromes provide insights into mechanisms of epileptogenesis, unrevealing the role of a number of genes with different functions, such as ion channels, proteins associated to the vesical synaptic cycle or involved in energy metabolism. The rapid progress of high-throughput genomic sequencing and corresponding analysis tools in molecular diagnosis are revolutionizing the practice and it is a fact that for some monogenic epilepsies the molecular confirmation may influence the choice of the treatment. Moreover, the novel genetic methods, that are able to analyze all known genes at a reasonable price, are of paramount importance to discover novel therapeutic avenues and individualized (or precision) medicine.
authors.affiliation: Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, ⿿G. Gaslini⿿ Institute, Genova, Italy. Electronic address: strianop@gmail.com.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.affiliation: Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, ⿿G. Gaslini⿿ Institute, Genova, Italy.
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Vari
authors.affiliation: Department of Pediatrics, University of L' Aquila, L⿿Aquila, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mazzocchetti
authors.affiliation: Department of Pediatrics, University of L' Aquila, L⿿Aquila, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Verrotti
authors.affiliation: Laboratory of Neurosciences and Neurogenetics, Department of Head and Neck Diseases, ⿿G. Gaslini⿿ Institute, Genova, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
mesh_terms: D000927:Anticonvulsants / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D057285:Precision Medicine
chemical_list: D000927:Anticonvulsants
keywords: Antiepileptic drugs; Epilepsy; Management; Pharmacogenomics; Precision medicine; Review; Treatment