{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:08:06Z","timestamp":1792195686471,"version":"4.4.0"},"reference-count":65,"publisher":"Wiley","issue":"S3","license":[{"start":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T00:00:00Z","timestamp":1578268800000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>SCN1A<\/jats:italic>, encoding the alpha 1 subunit of the sodium channel, is associated with several epilepsy syndromes and a range of other diseases. SCN1A represents the archetypal channelopathy associated with a wide phenotypic spectrum of epilepsies ranging from genetic epilepsy with febrile seizures plus (GEFS+), to developmental and epileptic encephalopathies (DEEs). SCN1A disorders also result in other diseases such as hemiplegic migraine and autism spectrum disorder (ASD). Dravet syndrome (DS) is the prototypic DEE with an early onset of febrile status epilepticus, hemiclonic or generalized tonic\u2010clonic seizures, and later onset of additional seizure types. Electroencephalography (EEG) and magnetic resonance imaging (MRI) are normal at onset. Development is normal in the first year of life but plateaus rapidly, with most patients ultimately having intellectual disability. Epilepsy is drug\u2010resistant and necessitates polytherapy. Most pathogenic variants occur de novo in the affected child, but they are inherited from mosaic affected or unaffected parents in rare cases. The molecular finding of haploinsufficiency is consistent with a loss\u2010of\u2010function defect in cells and animal models. Although seizures are the most commonly reported symptom in DS, many additional issues critically affect patients\u2019 cognitive and behavioral functioning. Hemiplegic migraine (HM) is a rare form of migraine with aura, characterized by the emergence of hemiparesis as part of the aura phase. All <jats:italic>SCN1A<\/jats:italic> mutations reported in sporadic\/familial HM3 are missense mutations. Most of the experimental results show that they cause a gain of function of Na<jats:sub>V<\/jats:sub>1.1 as opposed to the loss of function of the epileptogenic Na<jats:sub>V<\/jats:sub>1.1 mutations. <jats:italic>SCN1A<\/jats:italic> and <jats:italic>SCN2A<\/jats:italic> pathogenic variants have been identified in genetic studies of cohorts of patients with ASD. In addition, ASD features are often reported in patients with Dravet syndrome and other DEEs.<\/jats:p>","DOI":"10.1111\/epi.16386","type":"journal-article","created":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T12:23:36Z","timestamp":1578313416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":166,"title":["SCN1A\u2010related phenotypes: Epilepsy and beyond"],"prefix":"10.1111","volume":"60","author":[{"given":"Ingrid E.","family":"Scheffer","sequence":"first","affiliation":[{"name":"Departments of Medicine and Paediatrics Austin Health and Royal Children\u2019s Hospital Florey and Murdoch Children\u2019s Research Institute The University of Melbourne Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima","family":"Nabbout","sequence":"additional","affiliation":[{"name":"Reference Centre for Rare Epilepsies Department of Paediatric Neurology Necker Enfants Malades Hospital Imagine Institute U1163 Paris Descartes University Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,6]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/74159"},{"key":"e_1_2_16_3_1","first-page":"125","volume-title":"Epileptic Syndromes in Infancy. 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