Editing Epilepsy (section)

===Genetics===
Genetic causes of epilepsy are those in which a person’s genes directly contribute to the development of seizures. This includes cases where a specific mutation has been identified, as well as situations where the family history and clinical features strongly suggest a genetic basis, even if no known mutation is found. In the updated classification by the ILAE, the term genetic replaces the older term ''idiopathic'', to highlight that these epilepsies arise from inherited or spontaneous changes in a person’s biology — not from injury or infection.<ref name="Scheffer2017" />

Genetic factors are believed to contribute to many cases of epilepsy, either directly or by increasing vulnerability to other causes.<ref>{{cite journal |vauthors=Steinlein OK |date=2008-03-31 |title=Genetics and epilepsy |journal=Dialogues in Clinical Neuroscience |volume=10 |issue=1 |pages=29–38 |doi=10.31887/DCNS.2008.10.1/oksteinlein |pmc=3181863 |pmid=18472482}}</ref> Some forms are caused by a [[single-gene disorder|single gene defect]], which account for around 1–2% of cases. However, most are due to a combination of multiple genes and environmental influences.<ref name="Pand2011" /> Many of the genes known to play a role in epilepsy affect how brain cells send electrical signals, especially those involved in [[ion channel]]s, receptors, or signaling proteins.<ref name="Neuro2012" />

Genetics is believed to play an important role in epilepsies by a number of mechanisms. Simple and complex modes of [[heredity|inheritance]] have been identified for some of them. However, extensive screening have failed to identify many single [[gene]] variants of large effect.<ref>{{cite journal |vauthors=Heinzen EL, Depondt C, Cavalleri GL, Ruzzo EK, Walley NM, Need AC, Ge D, He M, Cirulli ET, Zhao Q, Cronin KD, Gumbs CE, Campbell CR, Hong LK, Maia JM, Shianna KV, McCormack M, Radtke RA, O'Conner GD, Mikati MA, Gallentine WB, Husain AM, Sinha SR, Chinthapalli K, Puranam RS, McNamara JO, Ottman R, Sisodiya SM, Delanty N, Goldstein DB |date=August 2012 |title=Exome sequencing followed by large-scale genotyping fails to identify single rare variants of large effect in idiopathic generalized epilepsy |journal=American Journal of Human Genetics |volume=91 |issue=2 |pages=293–302 |doi=10.1016/j.ajhg.2012.06.016 |pmc=3415540 |pmid=22863189}}</ref> More recent exome and genome sequencing studies have begun to reveal a number of de novo gene mutations that are responsible for some epileptic encephalopathies, including [[CHD2]] and [[SYNGAP1]]<ref>{{cite journal |vauthors=Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Møller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, Mefford HC |date=July 2013 |title=Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1 |journal=Nature Genetics |volume=45 |issue=7 |pages=825–830 |doi=10.1038/ng.2646 |pmc=3704157 |pmid=23708187}}</ref><ref>{{cite journal |vauthors=Chénier S, Yoon G, Argiropoulos B, Lauzon J, Laframboise R, Ahn JW, Ogilvie CM, Lionel AC, Marshall CR, Vaags AK, Hashemi B, Boisvert K, Mathonnet G, Tihy F, So J, Scherer SW, Lemyre E, Stavropoulos DJ |year=2014 |title=CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems |journal=Journal of Neurodevelopmental Disorders |volume=6 |issue=1 |pages=9 |doi=10.1186/1866-1955-6-9 |pmc=4022362 |pmid=24834135 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Suls A, Jaehn JA, Kecskés A, Weber Y, Weckhuysen S, Craiu DC, Siekierska A, Djémié T, Afrikanova T, Gormley P, von Spiczak S, Kluger G, Iliescu CM, Talvik T, Talvik I, Meral C, Caglayan HS, Giraldez BG, Serratosa J, Lemke JR, Hoffman-Zacharska D, Szczepanik E, Barisic N, Komarek V, Hjalgrim H, Møller RS, Linnankivi T, Dimova P, Striano P, Zara F, Marini C, Guerrini R, Depienne C, Baulac S, Kuhlenbäumer G, Crawford AD, Lehesjoki AE, de Witte PA, Palotie A, Lerche H, Esguerra CV, De Jonghe P, Helbig I |date=November 2013 |title=De novo loss-of-function mutations in CHD2 cause a fever-sensitive myoclonic epileptic encephalopathy sharing features with Dravet syndrome |journal=American Journal of Human Genetics |volume=93 |issue=5 |pages=967–975 |doi=10.1016/j.ajhg.2013.09.017 |pmc=3824114 |pmid=24207121}}</ref> and [[DNM1]], [[GABBR2]], [[Fatty acid synthase|FASN]] and [[RYR3]].<ref>{{cite journal |vauthors=((EuroEPINOMICS-RES Consortium)) |date=October 2014 |title=De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies |journal=American Journal of Human Genetics |volume=95 |issue=4 |pages=360–370 |doi=10.1016/j.ajhg.2014.08.013 |pmc=4185114 |pmid=25262651}}</ref>

Some genetic disorders, including [[phakomatoses]] such as [[Tuberous sclerosis|tuberous sclerosis complex]] and [[Sturge–Weber syndrome]], are strongly associated with epilepsy.<ref name="Stafstrom_2017">{{cite journal |vauthors=Stafstrom CE, Staedtke V, Comi AM |date=2017 |title=Epilepsy Mechanisms in Neurocutaneous Disorders: Tuberous Sclerosis Complex, Neurofibromatosis Type 1, and Sturge-Weber Syndrome |journal=Frontiers in Neurology |volume=8 |pages=87 |doi=10.3389/fneur.2017.00087 |pmc=5355446 |pmid=28367137 |doi-access=free}}</ref> These conditions are often discussed separately due to their multisystem involvement and high epilepsy burden.