Epilepsy and genetics

 N.B. there will be an easy read version, an infographic and translations at the bottom of this post

So this question seems to come up frequently on epilepsy facebook groups - is epilepsy hereditary?  N.B. a lot of the science here is applicable to other partly genetic, partly environmental conditions.

Well, for the most part, no is the simple answer.  There are a few specialist syndromes or conditions out there that are hereditary, but most forms of epilepsy are not.

This does not mean that genetics do not play a role.  There are a lot of genes that may 'predispose' (not directly cause) a person to have epilepsy which they may get from one or both parents.  But just because they have a 'predisposition' for it does not mean they will automatically get the condition.  Nor does it mean it's been passed on from a parent if a parent happens to have the condition too.  It requires other factors (environmental ones) to come into play.

Okay, so sometimes epilepsy might come about due to a mutation (because of environmental factors).  So there's a key difference between germ line cells and somatic cells here.  Germ line cells are those that go on to form the egg and sperm (and the gamete - the combined egg and sperm).  Somatic cells are EVERYTHING else.  If a gene variant is present or a mutation occurs in a germ line cell which goes on to form a gamete (and thus a new person), this variant will be present throughout that person's body INCLUDING in THEIR OWN germ line cells - thus it COULD be passed on to their own children.  So, the genes that predispose people to epilepsy get passed on through the germ line cells.

BUT, if a mutation takes place in a person's somatic cells (the rest of their cells) due to some environmental factor, (which acts on the genes that predispose the person to epilepsy and go on to cause the person to have seizures) - this WILL NOT get passed on.  Of course, if their child ends up having epilepsy (they too may be predisposed to the condition because they have some of those gene variants that caused their parents to be predisposed to the condition from their parents), it can very much look like it's been directly inherited.

You can get 'de novo' (new) mutations appear in the germ line which then get passed on.  So a family that wasn't genetically predisposed or didn't have a hereditary form of epilepsy previously, may all of a sudden seem to have it / be prone to it.

So I did say for the most part.  There are some exceptions where genes actually can be the cause of epilepsy and it is inherited.  This is by no means a comprehensive list.  But 2 inherited forms of epilepsy would be Dravet Syndrome and FAME1.  I find FAME1 quite interesting from a genetic point of view (that's my background).  I'll maybe try and go into this in a future post.  But even in hereditary conditions, there are other factors at work which may mean the person doesn't get the condition.  You have to factor in penetrance - this is basically how many people in a given population with a gene variant ACTUALLY show the traits / clinical symptoms associated with that variant).  So the gene variant for Dravet syndrome may only have a 90% penetrance, meaning only 90% of those with the variant for Dravet syndrome actually show the signs and symptoms for it even though they DO have the gene.  When penetrance is not 100% for a condition, it is called incomplete penetrance.  

Your head might be a little scrambled now as both these things are sort of saying you've inherited genes and you may / may not get the condition.  The major difference between the 2 is that with genetic predisposition, OTHER factors e.g. other genes or environmental factors (each contributing a small amount to a persons overall risk or getting the condition) must come into play.  With inheritance you need JUST the gene(s) specific to that condition.  I can talk a bit more about the factors that can affect the penetrance of a gene for a condition at another point.

Easy read

- Most forms of epilepsy are not hereditary with a few exceptions.

- However, there are many genes that do get passed on from parent to child that can cause a child to be 'predisposed' to epilepsy.

- Environment factors are required as well to trigger these genes.

- If someone has these genes right from the point of conception (when they were a gamete, the joined egg and sperm), the gene variants will be present in all their cells including their germ line cells (their egg / sperm cells).  This means they can be passed on.

- If a mutation occurs after this point in a somatic cell (all other cells in the body except the germ cells), this mutation will NOT get passed on.  So a mutation due to an environmental trigger that causes epilepsy in someone predisposed to it does not automatically mean their child will inherit the condition.

- There are inherited forms of epilepsy including Dravet syndrome and FAME1.

- However, even in inherited forms of epilepsy, it is not always a guarantee that a person will get the condition just because they've inherited the gene for it.  This is due to genetic penetrance.

- Penetrance is about how many people in a given population with a gene variant actually show the traits / clinical symptoms associated with that gene variant.

- It might be that the gene variant for Dravet syndrome has a penetrance of 90% - so 90% of people who inherit this gene will get Dravet syndrome.  This is called incomplete penetrance.

- Both incomplete penetrance and genetic predisposition can look the same - people have inherited genes and may / may not get the condition.  But...

- With genetic predisposition, you need OTHER factors e.g. other genes or environmental factors to interact with the gene variants (each contributing a small amount to a persons overall risk of getting the condition).

- With inheritance you JUST need the gene(s) specific to that condition.

Mandarin Chinese

• Da duo shu xing dian xing shi bu hui yi chuan, dan you shao shu li wai。

• Ran er, you xu duo ji yin ke yi cong fu mu chuan gei hai zi, bing ke shi hai zi dui xing dian xing chan sheng“yi gan xing” huo“yi yu”。

• Tong shi ye xu yao huan jing yin su lai chu fa zhe xie ji yin。

• Ru guo yi ge ren cong shou yun na yi ke（dang shi ta hai shi yi ge pei zi，ji jie he de luan zi he jing zi）jiu dai you zhe xie ji yin bian yi，na me zhe xie ji yin bian ti jiang cun zai yu ta de suo you xi bao zhong，包括 sheng zhi xi bao（luan zi huo jing zi）。Zhe yi wei zhe xie bian yi ke yi chuan gei xia yi dai。

• Ru guo zai zhe yi shi dian zhi hou，某个 ti xi bao（chu sheng zhi xi bao yi wai de qi ta suo you xi bao）fa sheng le bian yi，na me zhe zhong bian yi bu hui chuan gei xia yi dai。因此，由环境因素触发、在一个本身具有易感性的人身上导致癫痫的突变，并不意味着他们的孩子一定会遗传这种疾病。

• Cun zai yi chuan xing de xing dian xing，bao kuo Dravet zong he zheng he FAME1。

• Ran er，即使是 yi chuan xing de xing dian xing，yi ge ren ye bu yi ding hui yin wei ji cheng le zhe ge ji yin jiu huo de zhe zhong ji bing。这是因为存在遗传外显率。

• Wai xian lv（penetrance）shi zhi，在某个特定人群中，携带某种基因变异的人里，实际表现出与该基因变异相关的特征或临床症状的比例。

• Li ru，Dravet zong he zheng de ji yin bian yi wai xian lv ke neng shi 90%——ye jiu shi shuo，90% ji cheng le zhe ge ji yin de ren hui huo de Dravet zong he zheng。Zhe jiao zuo bu wan quan wai xian。

• Bu wan quan wai xian he yi chuan xing yi gan xing ke neng kan qi lai hen xiang——ren men ji cheng le mou xie ji yin，dan ke neng hui huo de，ye ke neng bu hui huo de zhe zhong ji bing。但是……

• Dui yu yi chuan xing yi gan xing lai shuo，hai xu yao qi ta yin su，li ru qi ta ji yin huo huan jing yin su，yu zhe xie ji yin bian yi hu xiang zuo yong（mei ge yin su dou zhi neng xiao fu du di zeng jia yi ge ren huo de zhe zhong ji bing de zong ti feng xian）。

• Er dui yu zhen zheng de yi chuan，zhi xu yao cheng zai yu gai ji bing zhi jie xiang guan de ji yin（huo ji yin）。

Hindi

• Adhikansh prakaar ki epilepsy vanshanugat nahi hoti, kuchh apvaadon ko chhodkar.

• Halaanki, aise bahut se genes hain jo mata-pita se bachche mein pass ho sakte hain aur bachche mein epilepsy ke prati "genetic predisposition" ya pravritti paida kar sakte hain.

• In genes ko trigger karne ke liye environmental factors ki bhi zarurat hoti hai.

• Agar kisi vyakti mein conception ke samay se hi ye genes maujood hain (jab woh ek gamete, yaani jude hue egg aur sperm se bana tha), to gene variants uske sharir ki sabhi cells mein maujood honge, jinmein germ line cells (uski egg ya sperm cells) bhi shaamil hain. Iska matlab hai ki ye variants aage pass kiye ja sakte hain.

• Agar iske baad kisi somatic cell mein mutation hota hai (yaani germ cells ke alawa sharir ki anya cells mein), to yeh mutation aage pass nahi hoga. Isliye, kisi environmental trigger ke kaaran kisi aise vyakti mein epilepsy paida karne wala mutation jismein pehle se genetic predisposition hai, iska matlab yeh nahi hai ki uska bachcha bhi automatically yeh condition inherit karega.

• Epilepsy ke kuchh inherited forms bhi hain, jinmein Dravet syndrome aur FAME1 shaamil hain.

• Halaanki, inherited epilepsy mein bhi sirf isliye ki kisi vyakti ne us condition se sambandhit gene inherit kiya hai, yeh zaroori nahi ki use woh condition ho hi jaaye. Yeh genetic penetrance ke kaaran hota hai.

• Penetrance ka matlab hai ki kisi given population mein kisi particular gene variant wale kitne log vastav mein us gene variant se jude traits ya clinical symptoms dikhate hain.

• Maan lijiye Dravet syndrome se sambandhit gene variant ki penetrance 90% hai. Iska matlab hai ki is gene ko inherit karne wale 90% logon ko Dravet syndrome hoga. Isse incomplete penetrance kaha jaata hai.

• Incomplete penetrance aur genetic predisposition dono ek jaise dikh sakte hain — logon ko kuchh genes virasat mein milte hain aur unhen condition ho bhi sakti hai aur nahi bhi. Lekin...

• Genetic predisposition mein, gene variants ke saath anya factors ki bhi zarurat hoti hai, jaise doosre genes ya environmental factors, jo gene variants ke saath interact karte hain. Har factor vyakti ke overall risk mein ek chhota sa hissa jodta hai.

• Inheritance mein, aapko keval us condition se seedhe sambandhit gene ya genes ki zarurat hoti hai.

Spanish

• La mayoría de las formas de epilepsia no son hereditarias, con algunas excepciones.

• Sin embargo, existen muchos genes que pueden transmitirse de padres a hijos y que pueden hacer que un niño tenga una "predisposición" a desarrollar epilepsia.

• También se necesitan factores ambientales para activar estos genes.

• Si una persona tiene estos genes desde el momento de la concepción (cuando era un gameto, es decir, el óvulo y el espermatozoide unidos), las variantes genéticas estarán presentes en todas sus células, incluidas sus células de la línea germinal (sus óvulos o espermatozoides). Esto significa que pueden transmitirse a sus hijos.

• Si se produce una mutación después de este momento en una célula somática (todas las demás células del cuerpo, excepto las células germinales), esta mutación no se transmitirá. Por lo tanto, una mutación causada por un factor ambiental que provoca epilepsia en una persona que ya tiene una predisposición genética no significa automáticamente que su hijo heredará la enfermedad.

• Existen formas hereditarias de epilepsia, entre ellas el síndrome de Dravet y FAME1.

• Sin embargo, incluso en las formas hereditarias de epilepsia, no siempre está garantizado que una persona desarrolle la enfermedad simplemente porque haya heredado el gen relacionado con ella. Esto se debe a la penetrancia genética.

• La penetrancia se refiere a cuántas personas de una población determinada que tienen una variante genética realmente presentan los rasgos o síntomas clínicos asociados con esa variante genética.

• Por ejemplo, la variante genética asociada al síndrome de Dravet podría tener una penetrancia del 90 %. Esto significa que el 90 % de las personas que heredan este gen desarrollarán el síndrome de Dravet. Esto se denomina penetrancia incompleta.

• Tanto la penetrancia incompleta como la predisposición genética pueden parecer similares: las personas han heredado determinados genes y pueden desarrollar o no la enfermedad. Pero...

• Con una predisposición genética, se necesitan otros factores, por ejemplo, otros genes o factores ambientales, que interactúen con las variantes genéticas. Cada uno de estos factores contribuye en pequeña medida al riesgo general de que una persona desarrolle la enfermedad.

• En la herencia genética, solo se necesita el gen o los genes específicos directamente relacionados con esa enfermedad.