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class="vector-toc-list"> <li id="toc-CACNB4" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#CACNB4"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.1</span> <span>CACNB4</span> </div> </a> <ul id="toc-CACNB4-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-GABRA1" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#GABRA1"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.2</span> <span>GABRA1</span> </div> </a> <ul id="toc-GABRA1-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-GABRD" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#GABRD"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.3</span> <span>GABRD</span> </div> </a> <ul id="toc-GABRD-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Myoclonin1/EFHC1" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Myoclonin1/EFHC1"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.4</span> <span>Myoclonin1/EFHC1</span> </div> </a> <ul id="toc-Myoclonin1/EFHC1-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Other_loci" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Other_loci"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.5</span> <span>Other loci</span> </div> </a> <ul id="toc-Other_loci-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Diagnosis" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Diagnosis"> <div class="vector-toc-text"> <span class="vector-toc-numb">5</span> <span>Diagnosis</span> </div> </a> <ul id="toc-Diagnosis-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Management" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Management"> <div class="vector-toc-text"> <span 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</div> </a> <ul id="toc-See_also-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> <span class="vector-toc-numb">10</span> <span>References</span> </div> </a> <ul id="toc-References-sublist" class="vector-toc-list"> </ul> </li> </ul> </div> </div> </nav> </div> </div> <div class="mw-content-container"> <main id="content" class="mw-body"> <header class="mw-body-header vector-page-titlebar"> <nav aria-label="Contents" class="vector-toc-landmark"> <div id="vector-page-titlebar-toc" class="vector-dropdown vector-page-titlebar-toc vector-button-flush-left" > <input type="checkbox" id="vector-page-titlebar-toc-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-page-titlebar-toc" class="vector-dropdown-checkbox " aria-label="Toggle the table of contents" > <label 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<div class="mw-indicators"> </div> <div id="siteSub" class="noprint">From Wikipedia, the free encyclopedia</div> </div> <div id="contentSub"><div id="mw-content-subtitle"></div></div> <div id="mw-content-text" class="mw-body-content"><div class="mw-content-ltr mw-parser-output" lang="en" dir="ltr"><div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Medical condition causing seizures</div> <div class="shortdescription nomobile noexcerpt noprint searchaux" style="display:none">Medical condition</div><style data-mw-deduplicate="TemplateStyles:r1257001546">.mw-parser-output .infobox-subbox{padding:0;border:none;margin:-3px;width:auto;min-width:100%;font-size:100%;clear:none;float:none;background-color:transparent}.mw-parser-output .infobox-3cols-child{margin:auto}.mw-parser-output .infobox .navbar{font-size:100%}@media screen{html.skin-theme-clientpref-night .mw-parser-output .infobox-full-data:not(.notheme)>div:not(.notheme)[style]{background:#1f1f23!important;color:#f8f9fa}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .infobox-full-data:not(.notheme) div:not(.notheme){background:#1f1f23!important;color:#f8f9fa}}@media(min-width:640px){body.skin--responsive .mw-parser-output .infobox-table{display:table!important}body.skin--responsive .mw-parser-output .infobox-table>caption{display:table-caption!important}body.skin--responsive .mw-parser-output .infobox-table>tbody{display:table-row-group}body.skin--responsive .mw-parser-output .infobox-table tr{display:table-row!important}body.skin--responsive .mw-parser-output .infobox-table th,body.skin--responsive .mw-parser-output .infobox-table td{padding-left:inherit;padding-right:inherit}}</style><table class="infobox ib-medical-condition"><tbody><tr><th colspan="2" class="infobox-above" style="background:#ccc">Juvenile myoclonic epilepsy</th></tr><tr><th scope="row" class="infobox-label">Other names</th><td class="infobox-data">Janz syndrome</td></tr><tr><th scope="row" class="infobox-label"><a href="/wiki/Medical_specialty" title="Medical specialty">Specialty</a></th><td class="infobox-data"><a href="/wiki/Neurology" title="Neurology">Neurology</a></td></tr></tbody></table> <p><b>Juvenile myoclonic epilepsy</b> (JME), also known as <b>Janz syndrome</b> or <b>impulsive petit mal</b>, is a form of hereditary, <a href="/wiki/Idiopathic_generalized_epilepsy" title="Idiopathic generalized epilepsy">idiopathic generalized epilepsy</a>,<sup id="cite_ref-Scheffer_1-0" class="reference"><a href="#cite_note-Scheffer-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> representing 5–10% of all epilepsy cases.<sup id="cite_ref-pana1994_2-0" class="reference"><a href="#cite_note-pana1994-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-camfield2013_3-0" class="reference"><a href="#cite_note-camfield2013-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> Typically it first presents between the ages of 12 and 18 with <a href="/wiki/Myoclonic_seizure" class="mw-redirect" title="Myoclonic seizure">myoclonic seizures</a> (brief, involuntary, single or multiple episodes of muscle contractions caused by abnormal excessive or synchronous neuronal activity in the brain).<sup id="cite_ref-pmid31611775_5-0" class="reference"><a href="#cite_note-pmid31611775-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> These events typically occur after awakening from sleep, during the evening or when sleep-deprived. JME is also characterized by <a href="/wiki/Generalized_tonic%E2%80%93clonic_seizure" title="Generalized tonic–clonic seizure">generalized tonic–clonic seizures</a>, and a minority of patients have <a href="/wiki/Absence_seizure" title="Absence seizure">absence seizures</a>.<sup id="cite_ref-Kastelinjn2013_6-0" class="reference"><a href="#cite_note-Kastelinjn2013-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> It was first described by <a href="/wiki/Th%C3%A9odore_Herpin" title="Théodore Herpin">Théodore Herpin</a> in 1857. Understanding of the genetics of JME has been rapidly evolving since the 1990s, and over 20 chromosomal loci and multiple genes have been identified.<sup id="cite_ref-pubmed.ncbi.nlm.nih.gov_7-0" class="reference"><a href="#cite_note-pubmed.ncbi.nlm.nih.gov-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> Given the genetic and clinical heterogeneity of JME some authors have suggested that it should be thought of as a spectrum disorder. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Epidemiology">Epidemiology</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=1" title="Edit section: Epidemiology"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The prevalence of JME is approximately 0.1–0.2 per 1,000, constituting approximately 5–10% of all epilepsies.<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> Some studies suggest that JME is slightly more common in females than males.<sup id="cite_ref-:0_9-0" class="reference"><a href="#cite_note-:0-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> The onset of symptoms ranges between the ages of 8 and 36 years, peaking between 12 and 18 years<sup id="cite_ref-camfield2013_3-1" class="reference"><a href="#cite_note-camfield2013-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> with a <a href="/wiki/Mean" title="Mean">mean</a> (average) of 15 years.<sup id="cite_ref-StatPearls_10-0" class="reference"><a href="#cite_note-StatPearls-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> Approximately 15% of children with <a href="/wiki/Childhood_absence_epilepsy" title="Childhood absence epilepsy">childhood absence epilepsy</a> and <a href="/wiki/Juvenile_absence_epilepsy" class="mw-redirect" title="Juvenile absence epilepsy">juvenile absence epilepsy</a> subsequently develop JME.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> In most cases, myoclonic jerks precede the first generalized tonic–clonic seizure by a mean of 3.3 years.<sup id="cite_ref-:1_12-0" class="reference"><a href="#cite_note-:1-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> A long-term population-based study suggested that 25 years after seizure onset, 17% of people with JME had all seizure types resolved, and 13% only experienced myoclonus despite having discontinued medication, meaning that approximately a third no longer had troublesome seizures.<sup id="cite_ref-:0_9-1" class="reference"><a href="#cite_note-:0-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> JME may be associated with an elevated prevalence of psychiatric disorders, including <a href="/wiki/Anxiety" title="Anxiety">anxiety</a>, <a href="/wiki/Mood_disorder" title="Mood disorder">mood disorders</a>, and <a href="/wiki/Personality_disorder" title="Personality disorder">personality disorders</a>.<sup id="cite_ref-StatPearls_10-1" class="reference"><a href="#cite_note-StatPearls-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Signs_and_symptoms">Signs and symptoms</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=2" title="Edit section: Signs and symptoms"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>There are three principal seizure types which may occur in JME: myoclonus, generalized tonic–clonic seizures and absence seizures. Approximately one-third of patients have all three seizure types.<sup id="cite_ref-:2_13-0" class="reference"><a href="#cite_note-:2-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> The majority of patients (58.2%) have frequent myoclonic jerks,<sup id="cite_ref-:2_13-1" class="reference"><a href="#cite_note-:2-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> with some sources stating that all patients with JME have myoclonic seizures.<sup id="cite_ref-StatPearls_10-2" class="reference"><a href="#cite_note-StatPearls-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> Generalized tonic–clonic seizures are less common<sup id="cite_ref-:2_13-2" class="reference"><a href="#cite_note-:2-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> but still reported in 85–90%.<sup id="cite_ref-StatPearls_10-3" class="reference"><a href="#cite_note-StatPearls-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> Absence seizures are believed to be least common, with an estimated prevalence between 10% and 40%.<sup id="cite_ref-:2_13-3" class="reference"><a href="#cite_note-:2-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-StatPearls_10-4" class="reference"><a href="#cite_note-StatPearls-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-14" class="reference"><a href="#cite_note-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> Seizures associated with JME tend to take place 30 minutes to an hour after waking up in the morning.<sup id="cite_ref-StatPearls_10-5" class="reference"><a href="#cite_note-StatPearls-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> Common triggers for JME seizures include lack of sleep, alcohol consumption, emotional stress, anxiety, and fatigue. A notable portion (30%–40%) of JME patients exhibit photosensitivity, whereby flashing lights from sources like sunlight, TV screens, and computers can provoke seizures. Individuals with photosensitivity tend to experience seizures at an earlier stage.<sup id="cite_ref-StatPearls_10-6" class="reference"><a href="#cite_note-StatPearls-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> Myoclonic <a href="/wiki/Status_epilepticus" title="Status epilepticus">status epilepticus</a> may occur as a complication but is uncommon. </p><p>Patients typically present to medical providers following their first generalized tonic–clonic seizure, by which time they have often had myoclonus for several years. The first generalized tonic–clonic seizure usually occurs in the context of a particular provoking factor, such as sleep deprivation, stress or alcohol consumption.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> Other potential provoking factors include "praxis induction" which is the precipitation of seizures or epileptiform discharges in the context of a complex cognitive tasks.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> Patients with JME tend to perform worse on neuropsychological assessments in multiple cognitive domains and are also more likely to have psychiatric comorbidities such as depression and anxiety when compared to control populations.<sup id="cite_ref-17" class="reference"><a href="#cite_note-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> The majority of patients with JME report satisfaction with their health, work, friendships and social life.<sup id="cite_ref-:0_9-2" class="reference"><a href="#cite_note-:0-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Cause">Cause</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=3" title="Edit section: Cause"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>JME is believed to be caused most often by multiple interacting genes rather than by a single genetic cause.<sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> Over twenty <a href="/wiki/Genetic_loci" class="mw-redirect" title="Genetic loci">genetic loci</a> have been implicated in the pathogenesis of JME.<sup id="cite_ref-pubmed.ncbi.nlm.nih.gov_7-1" class="reference"><a href="#cite_note-pubmed.ncbi.nlm.nih.gov-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> A minority of cases are caused by single genes inherited in an <a href="/wiki/Autosomal_dominant" class="mw-redirect" title="Autosomal dominant">autosomal dominant</a> fashion.<sup id="cite_ref-21" class="reference"><a href="#cite_note-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p><p>The majority of identified genes associated with JME encode for ion channel subunits.<sup id="cite_ref-22" class="reference"><a href="#cite_note-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> More recently, variants in intestinal cell kinase, which is encoded by a gene at chromosomal locus <i>6p12</i>, were found to be associated with JME. This gene is involved in <a href="/wiki/Mitosis" title="Mitosis">mitosis</a>, cell-cycle exit and radial neuroblast migration, as well as apoptosis.<sup id="cite_ref-23" class="reference"><a href="#cite_note-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> <a href="/wiki/EFHC1" title="EFHC1">EFHC1</a> has similar functions and is also associated with JME.<sup id="cite_ref-denijs2012_24-0" class="reference"><a href="#cite_note-denijs2012-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> These findings may explain subtle structural and functional brain abnormalities seen in patients with JME.<sup id="cite_ref-25" class="reference"><a href="#cite_note-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> </p><p>JME is distinct from other forms of genetic generalized epilepsy due to the prominence of myoclonus. There is evidence that patients with JME have hyperexcitable motor cortexes, most pronounced in the morning and after sleep deprivation.<sup id="cite_ref-26" class="reference"><a href="#cite_note-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> In addition, there is evidence that patients with JME have hyperexcitable and hyperconnected cortical networks that are involved in ictogenesis.<sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Genetics">Genetics</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=4" title="Edit section: Genetics"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="CACNB4">CACNB4</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=5" title="Edit section: CACNB4"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><i><a href="/wiki/CACNB4" title="CACNB4">CACNB4</a></i> is a gene that encodes the <a href="/wiki/Calcium_channel#.CE.B2_subunit" title="Calcium channel">calcium channel β4 subunit</a> protein. It has been associated with JME though it is not strictly considered a putative JME gene because its mutation did not segregate in affected family members, it was found in only one member of a JME family from Germany, and the finding has not been replicated.<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> </p><p>β subunits are important regulators of calcium channel current amplitude, voltage dependence, and they also regulate channel trafficking.<sup id="cite_ref-30" class="reference"><a href="#cite_note-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> In mice, a naturally occurring null mutation leads to the "lethargic" phenotype. This is characterized by <a href="/wiki/Ataxia" title="Ataxia">ataxia</a> and lethargic behavior at early stages of development followed within days by the onset of focal motor seizures and episodes of behavioral immobility correlated with patterns of cortical spike and wave discharges on <a href="/wiki/Electroencephalography" title="Electroencephalography">electroencephalography</a> (EEG)<sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup> A premature-termination mutation, R482X, was identified in a patient with JME while an additional <a href="/wiki/Missense_mutation" title="Missense mutation">missense mutation</a> C104F was identified in a German family with generalized epilepsy and praxis-induced seizures.<sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> The R482X mutation causes increased current amplitudes and an accelerated fast time constant of inactivation.<sup id="cite_ref-Etemad2014_33-0" class="reference"><a href="#cite_note-Etemad2014-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> Whether these modest functional differences may be in charge of JME remains to be established.<sup id="cite_ref-Etemad2014_33-1" class="reference"><a href="#cite_note-Etemad2014-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="GABRA1">GABRA1</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=6" title="Edit section: GABRA1"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/GABRA1" class="mw-redirect" title="GABRA1">GABRA1</a> is a gene that encodes for an α subunit of the <a href="/wiki/GABAA_receptor" title="GABAA receptor">GABA<sub>A</sub> receptor</a> protein, which encodes one of the major inhibitory neurotransmitter receptors. There is one known mutation in this gene that is associated with JME, A322D, located in the third segment of the protein.<sup id="cite_ref-Cossette_2002_34-0" class="reference"><a href="#cite_note-Cossette_2002-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> This missense mutation results in channels with reduced peak GABA-evoked currents.<sup id="cite_ref-macdonald2012_35-0" class="reference"><a href="#cite_note-macdonald2012-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> Furthermore, the presence of such mutation alters the composition and reduces the expression of wild-type GABA<sub>A</sub> receptors.<sup id="cite_ref-macdonald2012_35-1" class="reference"><a href="#cite_note-macdonald2012-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="GABRD">GABRD</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=7" title="Edit section: GABRD"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p><a href="/wiki/GABRD" title="GABRD">GABRD</a> encodes the δ subunit of the <a href="/wiki/GABA_receptor" title="GABA receptor">GABA receptor</a>, which is an important constituent of the GABA<sub>A</sub> receptor mediating tonic inhibition in neurons (extrasynaptic GABA receptors, i.e. receptors located outside the synapse).<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> Among the mutations that have been reported in this in this gene, one (R220H) has been identified in a small family with JME. This mutation affects GABAergic transmission by altering the surface expression of the receptor as well as reducing the channel opening duration. </p> <div class="mw-heading mw-heading3"><h3 id="Myoclonin1/EFHC1"><span id="Myoclonin1.2FEFHC1"></span>Myoclonin1/EFHC1</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=8" title="Edit section: Myoclonin1/EFHC1"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Myoclonin1/<a href="/wiki/EFHC1" title="EFHC1">EFHC1</a> encodes for a protein involved in cell division, neuroblast migration and synapse/dendrite formation. EFHC1 is expressed in many tissues, including the brain, where it is localized to the <a href="/wiki/Soma_(biology)" title="Soma (biology)">soma</a> and <a href="/wiki/Dendrite" title="Dendrite">dendrites</a> of neurons, particularly the <a href="/wiki/Hippocampus" title="Hippocampus">hippocampal CA1</a> region, <a href="/wiki/Pyramidal_neurons" class="mw-redirect" title="Pyramidal neurons">pyramidal neurons</a> in the <a href="/wiki/Cerebral_cortex" title="Cerebral cortex">cerebral cortex</a>, and <a href="/wiki/Purkinje_cell" title="Purkinje cell">Purkinje cells</a> in the <a href="/wiki/Cerebellum" title="Cerebellum">cerebellum</a>.<sup id="cite_ref-denijs2012_24-1" class="reference"><a href="#cite_note-denijs2012-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p><p>There are four JME-causing mutations discovered (D210N, R221H, F229L and D253Y). The mutations do not seem to alter the ability of the protein to colocalize with centrosomes and mitotic spindles but induce mitotic spindle defects. Moreover, the mutations impact radial and tangential migration during brain development.<sup id="cite_ref-denijs2012_24-2" class="reference"><a href="#cite_note-denijs2012-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> As such a theory has been put forward that JME may be the result of a brain developmental disorder.<sup id="cite_ref-denijs2012_24-3" class="reference"><a href="#cite_note-denijs2012-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Other_loci">Other loci</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=9" title="Edit section: Other loci"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Three SNP alleles in BRD2, Cx-36 and ME2 and microdeletions in 15q13.3, 15q11.2 and 16p.13.11 also contribute risk to JME.<sup id="cite_ref-delgado2013_37-0" class="reference"><a href="#cite_note-delgado2013-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Diagnosis">Diagnosis</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=10" title="Edit section: Diagnosis"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Diagnosis is typically made based on patient history. Physical examination is usually normal.<sup id="cite_ref-StatPearls_10-7" class="reference"><a href="#cite_note-StatPearls-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> Misdiagnosis can occur if myoclonic seizures mistaken for muscle twitches or feelings of anxiety/nervousness.<sup id="cite_ref-StatPearls_10-8" class="reference"><a href="#cite_note-StatPearls-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> </p><p>The primary diagnosis for JME is a good knowledge of patient history and the <a href="/wiki/Neurologist" class="mw-redirect" title="Neurologist">neurologist's</a> familiarity with the myoclonic jerks, which are the hallmark of the syndrome.<sup id="cite_ref-38" class="reference"><a href="#cite_note-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> Additionally, an EEG will indicate a characteristic pattern of waves and spikes associated with the syndrome such as generalized 4–6 Hz polyspike and slow wave discharges. These discharges may be evoked by photic stimulation (blinking lights) or hyperventilation. </p><p>Both <a href="/wiki/Magnetic_resonance_imaging" title="Magnetic resonance imaging">magnetic resonance imaging</a> (MRI) and <a href="/wiki/Computer_tomography" class="mw-redirect" title="Computer tomography">computer tomography</a> (CT) scans generally appear normal in JME patients. However a number of quantitative MRI studies have reported focal or regional abnormalities of the subcortical and cortical grey matter, particularly the thalamus and frontal cortex, in JME patients.<sup id="cite_ref-39" class="reference"><a href="#cite_note-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Positron_emission_tomography" title="Positron emission tomography">Positron emission tomography</a> (PET) reports in some patients may indicate local deviations in many transmitter systems.<sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Management">Management</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=11" title="Edit section: Management"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The most effective anti-epileptic medication for JME is <a href="/wiki/Valproic_acid" class="mw-redirect" title="Valproic acid">valproic acid</a> (Depakote).<sup id="cite_ref-tomson2016_41-0" class="reference"><a href="#cite_note-tomson2016-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-:1_12-1" class="reference"><a href="#cite_note-:1-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> Due to valproic acid's <a href="/wiki/Teratogen" class="mw-redirect" title="Teratogen">high incidence of fetal malformations</a>,<sup id="cite_ref-42" class="reference"><a href="#cite_note-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-tomson2016_41-1" class="reference"><a href="#cite_note-tomson2016-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> women of child-bearing age may be started on alternative medications such as <a href="/wiki/Lamotrigine" title="Lamotrigine">lamotrigine</a> or <a href="/wiki/Levetiracetam" title="Levetiracetam">levetiracetam</a>. <a href="/wiki/Carbamazepine" title="Carbamazepine">Carbamazepine</a> may aggravate generalized genetic epilepsies and its use should be avoided in JME. Treatment is generally lifelong but follow-up of a subgroup of patients found that they were seizure-free and off anti-epileptic drugs.<sup id="cite_ref-43" class="reference"><a href="#cite_note-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-44" class="reference"><a href="#cite_note-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-45" class="reference"><a href="#cite_note-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> Patients should be warned to avoid sleep deprivation. </p> <div class="mw-heading mw-heading2"><h2 id="History">History</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=12" title="Edit section: History"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The first citation of JME was made in 1857 when <a href="/wiki/Th%C3%A9odore_Herpin" title="Théodore Herpin">Théodore Herpin</a> described a 13-year-old boy with myoclonic jerks, which progressed to tonic–clonic seizures three months later.<sup id="cite_ref-emedicine_46-0" class="reference"><a href="#cite_note-emedicine-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> In 1957, Janz and Christian published a journal article describing several patients with JME.<sup id="cite_ref-47" class="reference"><a href="#cite_note-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> The name Juvenile Myoclonic Epilepsy was proposed in 1975 and adopted by the <a href="/wiki/International_League_Against_Epilepsy" title="International League Against Epilepsy">International League Against Epilepsy</a>.<sup id="cite_ref-emedicine_46-1" class="reference"><a href="#cite_note-emedicine-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Culture">Culture</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=13" title="Edit section: Culture"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Stand-up comedian <a href="/wiki/Maisie_Adam" title="Maisie Adam">Maisie Adam</a> has JME and discussed it in her award-winning show "Vague".<sup id="cite_ref-48" class="reference"><a href="#cite_note-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup> </p><p>The 2018 documentary film <i>Separating The Strains</i> dealt with the use of <a href="/wiki/CBD_oil" class="mw-redirect" title="CBD oil">CBD oil</a> to treat symptoms of JME.<sup id="cite_ref-49" class="reference"><a href="#cite_note-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup> Currently, no scientific evidence exists to support use of <a href="/wiki/CBD_oil" class="mw-redirect" title="CBD oil">CBD oil</a> to treat symptoms of JME. </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=14" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Progressive_myoclonus_epilepsies" class="mw-redirect" title="Progressive myoclonus epilepsies">Progressive myoclonus epilepsies</a></li> <li><a href="/wiki/Spinal_muscular_atrophy_with_progressive_myoclonic_epilepsy" title="Spinal muscular atrophy with progressive myoclonic epilepsy">Spinal muscular atrophy with progressive myoclonic epilepsy</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Juvenile_myoclonic_epilepsy&action=edit&section=15" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist"> <div class="mw-references-wrap mw-references-columns"><ol class="references"> <li id="cite_note-Scheffer-1"><span class="mw-cite-backlink"><b><a href="#cite_ref-Scheffer_1-0">^</a></b></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output 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