[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-465541-105":59,"doc-detail-465541-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","neurologists-black-swan-molecular-basis-of-prenatal-seizures","Neurologist’s Black Swan - Molecular Basis of Prenatal Seizures","","Seizures with prenatal manifestations represent an infrequently studied but clinically severe epilepsy phenotype. Knowledge of epilepsy genetics and classification has expanded rapidly, yet fetal epilepsy cases remain underrepresented, even with many reports from the last two decades. Only SCN2A and SCN8A have been reliably linked to pathogenic variants causing fetal epilepsy, leaving the broader genetic landscape unresolved. This review surveys molecular foundations of prenatal-onset epilepsy and emphasizes that fetal seizure prevalence is likely underestimated; timely diagnosis is critical for outcomes.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/neurologists-black-swan-molecular-basis-of-prenatal-seizures/465541/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/neurologists-black-swan-molecular-basis-of-prenatal-seizures/465541.png","ImageObject",300,407,{"name":92,"@type":93},"WPS_1786070896","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are fetal seizures difficult to diagnose early?","Question",{"text":112,"@type":113},"Non-invasive prenatal diagnostic tools have limited sensitivity and specificity. Routine ultrasonography often cannot reliably detect seizures in utero, and maternal perception is subjective, making early diagnosis challenging.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which genes have been most reliably linked to fetal epilepsy?",{"text":117,"@type":113},"To date, pathogenic variants reliably related to fetal epilepsy have been shown for only two genes: SCN2A and SCN8A.",{"name":119,"@type":110,"acceptedAnswer":120},"How do voltage-gated sodium channels relate to prenatal-onset seizures?",{"text":121,"@type":113},"Voltage-gated sodium channels in the CNS are encoded by SCN family genes, including SCN2A and SCN8A. Developmental changes in their expression, localization, isoforms, and functional properties are critical for nervous system maturation, and pathogenic variants in this family are implicated in epileptic and neurodevelopmental disorders.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},465541,1790982974,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},549768072016,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Review  \nNeurologist’s Black Swan: Molecular Basis of Prenatal Seizures  \nAngelina O. Kustova 1, Alexandra D. Medyanik 1, Polina E. Anisimova 1, Victor S. Tarabykin 1,2, * and Elena V. Kondakova 1,2  \nAcademic Editor: KarolyOrban-Kis  \nReceived: 21 November 2025  \nRevised: 23 December 2025  \nAccepted: 24 December 2025  \nPublished: 26 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia; [elakust@gmail.com](elakust@gmail.com) (A.O.K.); [al.medyanik111@gmail.com](al.medyanik111@gmail.com) (A.D.M.); [polina.adyasova@yandex.ru](polina.adyasova@yandex.ru) (P.E.A.)  \n2 Department of Genetics and Life Sciences, Sirius University of Science and Technology, 1 Olympic Ave, 354340 Sochi, Russia  \n* Correspondence: [tarabykin.vs@talantiuspeh.ru](tarabykin.vs@talantiuspeh.ru)  \nAbstract  \nOne of the least studied but clinically severe forms of epilepsy is seizures with prenatal manifestations. Our understanding of epilepsy disorders has advanced substantially; numerous disease-associated genes have been identified, classifications have been refined, and underlying mechanisms and diagnostic approaches have been elucidated. However, one group of patients—those with seizures before the birth—has remained largely overlooked by researchers, despite numerous similar clinical cases reported over the past two decades. To date, only two genes, SCN2A and SCN8A, have been shown to have pathogenic variants that are reliably related to fetal epilepsy. Yet, how many genes are truly involved? This review will examine the known molecular foundations of epilepsy with prenatal onset. The prevalence of fetal seizures in patients with epilepsy is likely underestimated, although timely diagnosis of the disease is crucial for patient outcomes.  \nKeywords: fetal seizures; epilepsy; developmental and epileptic encephalopathies; pathogenic variant; voltage-gated sodium channels  \n1. Introduction  \nHistorically, fetal seizures were considered to be associated primarily with external factors such as infections, exposure to toxins, or metabolic abnormalities [1] . As for genetic reasons, prenatal onset of epilepsy is uncharted territory [2–7] . The limited availability of non-invasive prenatal diagnostic techniques makes early detection of seizures particularly challenging. Routine ultrasonography, even when performed during a suspected episode, has low sensitivity and specificity for detecting seizures in utero. Emerging non-invasive techniques, such as fetal magnetoencephalography, remain technically challenging and are available only in a limited number of centers. Maternal perception is inherently subjective and may reflect either epileptic activity or benign fetal movements such as hiccups, turns, or sleep-related movements [8,9] .  \nAs a result, fetal seizure diagnosis is often retrospective and inferential, relying on indirect indicators such as stereotypy and recurrence of movements, their persistence across fetal behavioral states, and subsequent postnatal confirmation of epilepsy or structural brain abnormalities. The absence of validated screening and verification tools contributes to substantial underdiagnosis, delaying appropriate clinical management and limiting opportunities for prenatal intervention. In this context, identifying reliable genetic markers associated with fetal seizures becomes particularly important.  \nTo date, there are many known cases of fetal epilepsy. Unfortunately, genetic analyses have not been performed in most instances. The first such clinical case was published in 1996 [10] . At 32 weeks of gestation, during an ultrasound examination, clinicians observed idiopathic polyhydramnios and fetal seizures characterized by rapid, repetitive lim","cbCaisvx5b0KlZQ6","https://ap.wps.com/l/cbCaisvx5b0KlZQ6","pdf",1497647,18,"English","# Introduction\n## Prenatal seizure diagnosis challenges\n## Genetic foundations and known fetal epilepsy genes\n## Voltage-gated sodium channels and SCNxA-related disorders","[{\"question\":\"Why are fetal seizures difficult to diagnose early?\",\"answer\":\"Non-invasive prenatal diagnostic tools have limited sensitivity and specificity. Routine ultrasonography often cannot reliably detect seizures in utero, and maternal perception is subjective, making early diagnosis challenging.\"},{\"question\":\"Which genes have been most reliably linked to fetal epilepsy?\",\"answer\":\"To date, pathogenic variants reliably related to fetal epilepsy have been shown for only two genes: SCN2A and SCN8A.\"},{\"question\":\"How do voltage-gated sodium channels relate to prenatal-onset seizures?\",\"answer\":\"Voltage-gated sodium channels in the CNS are encoded by SCN family genes, including SCN2A and SCN8A. Developmental changes in their expression, localization, isoforms, and functional properties are critical for nervous system maturation, and pathogenic variants in this family are implicated in epileptic and neurodevelopmental disorders.\"}]","Neurologist’s Black Swan - Molecular Basis of Prenatal Seizures | PDF",1790769751,45]