Can Epilepsy be genetic? Can Epilepsy be inherited?

Can Epilepsy be genetic?

Yes.

We get our genes from our Parents. They determine a lot of our features: our height, our skin colour, our eye colour, hair colour and so on. Genes also contain the information required to make the brain, the lungs, the liver and other organs of our body.

Therefore, if we have abnormal genes while growing up, we may develop abnormalities of the brain. We are now discovering that in many patients, the cause of Epilepsy is abnormal genes.

Abnormal Genes can produce Epilepsy by one of 3 mechanisms. The table below has one example of each mechanism:

Abnormal Gene

Mechanism: How it causes Epilepsy

Epilepsy Syndrome that it produces

SCN1A Abnormal Brain Cells: Abnormal Sodium channels in brain cells Dravet syndrome
ADGRG-1 Abnormal Arrangement of Brain cells: Too many wrinkles on the surface of the brain Polymicrogyria
SLC2A1 Metabolic (chemical) problems: Problems in transporting glucose to the brain GLUT-1 deficiency syndrome

To know more about these mechanisms/genes, read this article:

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Can Epilepsy be hereditary?

The word hereditary means passed on from Parents to Children.

I told you that many people with Epilepsy have abnormal genes. Still, it is an excellent surprise that if you have Epilepsy, the chance that you will pass it on to your child is very low.

Why is it so? It is because your child will receive two sets of genes – one from you and another from your partner.

In most cases, even if one of these sets is normal, the child will not have Epilepsy. This is called the “Recessive” nature of a gene. The harmful effect of an abnormal gene is prevented by a normal gene from your husband/wife. Luckily, many of the genes causing Epilepsy are Recessive.

However, some genes can be “Dominant” in nature – this means that even if one of the parents has Epilepsy, the child is likely to have Epilepsy.

Here is a quite complete list of the dominantly inherited Epilepsies. Like many of the tables on this site, you can just glance through it rather than memorizing it. The critical thing to note is that it is relatively small.

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Dominant Genes causing Epilepsy:

Abnormal Gene

Mechanism: Which channel is affected

Epilepsy Syndrome that it produces

Mostly Generalized Seizures:
KCNQ2, 3 Abnormal Potassium channels on cells Benign Familial Neonatal Convulsions
SCN2A Abnormal Sodium channels Benign Familial Neonatal-Infantile Seizures
SCN1A, 2A, 2B, GABRG2 Same as above Generalized Epilepsy with Febrile Seizures Plus (GEFS+)
SCN1A Same as above Dravet Syndrome
GABRA1, EFHC1, CACNB3, CLCN2 & others Abnormal Chloride/Calcium channels Juvenile Myoclonic Epilepsy (JME)
Focal Seizures only:
TSC – 1&2 Unknown Tuberous Sclerosis
CHRNA – 2,4, B2, KCNT1 Acetylcholine receptors / Potassium channels Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE)
LG11 Abnormal Potassium Channels Autosomal Dominant Epilepsy with Auditory features (ADEAF)
Unknown (?GABRG2) Unknown Familial Mesial Temporal Lobe Epilepsy (FMTLE)
DEPDC5 Abnormal signalling pathways inside cells Familial Focal Epilepsy with Variable Foci (FEVF)

Overall, how commonly is Epilepsy inherited?

For the reasons mentioned above, most people do not have a family history of Epilepsy. Rephrasing this: Most children of patients with Epilepsy do not develop Epilepsy.

One study done in Italy found that if you have Epilepsy, only 2.5% of your close relatives (parents, siblings, children) will have Epilepsy (Bianchi et al. 2003).

  • More than 95% of babies of parents with epilepsy, will not have Epilepsy.

  • It is pertinent to remember that overall about 1% of babies are anyway born with Epilepsy.

The risk of your children getting Epilepsy is higher if you have one of the “Dominant” genes mentioned above. Overall, it is more common if you have an Epilepsy syndrome with only generalized seizures, e.g. JME.

However, even if you have one of these “Dominant” abnormal genes, the chance that your child will develop Epilepsy is not 100%. This is because of another helpful phenomenon called “incomplete penetrance” (read more by clicking here). For JME, the news is excellent: Only 6.6% of children of Parents with JME develop JME themselves (Janz et al. 1992). The penetrance of other genes is as follows:

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Abnormal Gene

Epilepsy Syndrome that it produces

Chances that your Child will have Epilepsy

Mostly Generalized Seizures:
KCNQ2, 3 Benign Familial Neonatal Convulsions 80%
SCN2A Benign Familial Neonatal-Infantile Seizures Variable
SCN1A, 2A, 2B, GABRG2 Generalized Epilepsy with Febrile Seizures Plus (GEFS+) 80%
SCN1A Dravet Syndrome Unknown
GABRA1, EFHC1, CACNB3, CLCN2, Juvenile Myoclonic Epilepsy (JME) 6%
Focal Seizures only:
TSC – 1&2 Tuberous Sclerosis 100%
CHRNA – 2,4, B2, KCNT1 Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (ADNFLE) 60 – 80%
LG11 Autosomal Dominant Epilepsy with Auditory features (ADEAF) 60 – 80%
Unknown (?GABRG2) Familial Mesial Temporal Lobe Epilepsy (FMTLE) 60%
DEPDC5 Familial Focal Epilepsy with Variable Foci (FEVF) 60%

Is Epilepsy more likely to be inherited if the Parents are related (Consanguinous Marriages)?

As noted earlier, the inheritance of Epilepsy is not very common because the child does get two sets of genes, one from each Parent. Usually, the two parents are very different from each other – they have very different genes from one another. What happens when parents have similar genes?

Marriage between two people who are closely related to each other is called a “Consanguinous Marriage”. If the two parents are closely related to each other (e.g. are Cousins), then they are genetically similar (have similar genes).

Then, the chance that the child will get the same set of abnormal genes from both parents increases. Therefore, the possibility that the child will get Epilepsy increases. Thus inheritance of Epilepsy is more common when the parents are closely related to each other.

Should all patients with Epilepsy have Genetic Testing?

No, not as of now (April 2020).

The question of which patients should get genetic testing is hotly debated, even amongst doctors. We just don’t know the answer yet.

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If there is a strong family history of Epilepsy, many doctors will advise genetic testing. Here is how genetic testing may affect you:

  • It may identify your Epilepsy Syndrome conclusively.
  • Rarely, it may help in selecting the right medications.
  • Some researchers believe that genes may affect the outcome of surgery.
  • It may help to estimate the chances of your Child getting Epilepsy.

Genetic testing is gradually becoming more widely available. Now, certain doctors have started recommending testing at critical junctures, even if there is no family history. For example:

  • When medications are not working.
  • Before undergoing Epilepsy surgery.

It is important to remember that genetic testing is expensive, we cannot test for all mutations which cause Epilepsy, and at this point, it may not be possible to tailor your treatment based on your genes. However, it is also reasonable to expect that all these problems will have solutions in the future.

 

Footnote: In some cases, the genes from both parents are perfectly normal. But while the baby is growing in the womb, his/her normal genes may become abnormal. These are called “Somatic mutations”. This is a developing concept in Epilepsy, and therefore not discussed in detail here.

 


Caution:
This information is for educational purposes. It is not a substitute for professional medical diagnosis & treatment. Do not change your medications, supplements or other treatments without your doctor's permission.

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Dr. Siddharth Kharkar

Dr. Siddharth Kharkar is a board certified (American Board of Psychiatry & Neurology certified) Neurologist. He is a Epilepsy specialist & Parkinson's specialist in Mumbai, Maharashtra, India.

He has trained in the best institutions in India, US and UK including KEM hospital in Mumbai, Johns Hopkins University in Baltimore, University of California at San Francisco (UCSF), USA & Kings College in London.

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