Functional gene enrichment and network analysis.

<p>Significant gene-set enrichments on 329 genes deleted in GGE patients revealed an enrichment of GRIN2B interacting proteins, genes of the MGI abnormal emotion/affect behaviour annotation and of the GO cognition annotation. Segmental clusters of genes belonging to a gene family were removed. Positional clustering of genes physically linked on a microdeletion is indicated by a slash between the gene symbols.</p><p>Functional gene enrichment and network analysis.</p

Gene-disrupting microdeletions found only in patients with genetic generalised epilepsy.

<p>GGE, genetic generalised epilepsy; CTR: population control; Chr: chromosome, start/end: genomic start and end point of the deleted segment, hg19; ^<i>P</i>-value: type-1 error rate for a χ2-test with df = 1; OR, 95%-CI, odds ratio with 95% confidence interval. Disease phenotype: ASD: autism spectrum disorder, ADHD: attention deficit hyperactivity disorder, AN: anorexia nervosa, AUT: autism, BPD: bipolar disorder, EE: epileptic encephalopathy, EPI: epilepsy, ID: intellectual disability, MCP: microcephaly, SCZ: schizophrenia; GGE syndromes: CAE: childhood absence epilepsy, JAE: juvenile absence epilepsy, JME: juvenile myoclonic epilepsy, EGMA: epilepsy with generalised tonic-clonic seizures alone predominantly on awakening, EGTCS: epilepsy with generalised tonic-clonic seizures alone, gsw: generalised spike and wave discharges on the electroencephalogram, number/: age-at-onset of afebrile generalised seizures. # previously published in [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005226#pgen.1005226.ref026" target="_blank">26</a>] and * [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005226#pgen.1005226.ref027" target="_blank">27</a>]. Bold gene symbols indicate genes previously implicated in epileptogenesis.</p><p>Gene-disrupting microdeletions found only in patients with genetic generalised epilepsy.</p

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new “Integrated Epilepsy Classification”?

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the “Four-dimensional epilepsy classification” (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the “Integrated Epilepsy Classification”. This consists of five categories derived to different degrees from both of the classification systems: 1) a “Headline” summarizing localization and etiology for the less specialized users, 2) “Seizure type(s)”, 3) “Epilepsy type” (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) “Etiology”, and 5) “Comorbidities & patient preferences”