Abstract
BackgroundSeveral genetic association investigations have been performed over the last three decades to identify variants underlying Juvenile Myoclonic Epilepsy (JME). Here, we evaluate the accumulating findings and provide an updated perspective of these studies.MethodologyA systematic literature search was conducted using the PubMed, Embase, Scopus, Lilacs, epiGAD, Google Scholar and Sigle up to February 12, 2016. The quality of the included studies was assessed by a score and classified as low and high quality. Beyond outcome measures, information was extracted on the setting for each study, characteristics of population samples and polymorphisms.ResultsFifty studies met eligibility criteria and were used for data extraction. With a single exception, all studies used a candidate gene approach, providing data on 229 polymorphisms in or near 55 different genes. Of variants investigating in independent data sets, only rs2029461 SNP in GRM4, rs3743123 in CX36 and rs3918149 in BRD2 showed a significant association with JME in at least two different background populations. The lack of consistent associations might be due to variations in experimental design and/or limitations of the approach.ConclusionsThus, despite intense research evidence established, specific genetic variants in JME susceptibility remain inconclusive. We discussed several issues that may compromise the quality of the results, including methodological bias, endophenotype and potential involvement of epigenetic factors.PROSPERO registration numberCRD42016036063
Highlights
Juvenile Myoclonic Epilepsy (JME) has been recognized by the International League Against Epilepsy (ILAE) as an epileptic syndrome since 1989[1,2] and represents 5% to 10% of all epilepsies[3]
Of variants investigating in independent data sets, only rs2029461 single nucleotide polymorphism (SNP) in glutamate receptor (GRM4), rs3743123 in CX36 and rs3918149 in Bromodomain Containing 2 (BRD2) showed a significant association with JME in at least two different background populations
Diagnostic criteria differ between epileptologists, it is widely agreed that JME sufferers have early-morning myoclonic seizures (MC) with or without other seizure types[2,6,7]
Summary
Juvenile Myoclonic Epilepsy (JME) has been recognized by the International League Against Epilepsy (ILAE) as an epileptic syndrome since 1989[1,2] and represents 5% to 10% of all epilepsies[3]. Diagnostic criteria differ between epileptologists, it is widely agreed that JME sufferers have early-morning myoclonic seizures (MC) with or without other seizure types (i.e., generalized tonic–clonic seizures and less frequent absences)[2,6,7]. Electroencephalography (EEG) has revealed interictal generalized spike-wave discharges (SWD) and normal background activity for patients with a typical history of JME[8,9]. Several genetic association investigations have been performed over the last three decades to identify variants underlying Juvenile Myoclonic Epilepsy (JME). We evaluate the accumulating findings and provide an updated perspective of these studies
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