Facts on Genetics and Epilepsy

chromosomes

INTRODUCTION

A common question that we receive in clinic relates to the chance that a parent will “pass on” their epilepsy to their children. Also, if one child has epilepsy, will their brother or sister develop epilepsy? These are important questions. The answer is, of course, complicated. The answers to such questions must be tailored to the individual/family.

GENERAL FACTS ABOUT THE RISK OF DEVELOPING EPILEPSY:

  • Remember: For the general population, the risk of developing epilepsy is approximately 1%. I always remind patients and families- even without a known family history of epilepsy or known genetic reason for epilepsy, any parent could have a child with epilepsy. Compare the 1% chance of epilepsy (for all people in the general population) to the higher risk groups described below.
  • The risk of epilepsy is higher in the offspring of a mother with epilepsy compared to a father with epilepsy:
    • If mother has epilepsy, the risk of epilepsy in her children:
      • 2.9%-8.7%
    • If father has epilepsy, the risk of epilepsy in his children
      • 1.0%-3.6%

  • If a parent has epilepsy, the risk of epilepsy in his or her daughter(s) is somewhat higher compared to the risk in son(s).

  • If a parent develops epilepsy at a young age, the risk of epilepsy in his or her children is higher. An example may help clarify this: Let’s look at two fathers with epilepsy. Let’s compare the risk of these two fathers having a child with epilepsy. Father #1’s epilepsy began when he was 8 years old. Father #2’s epilepsy began at the age of 29 years of age. The father with the younger age of onset (Father #1) will have a higher risk of having a child/children with epilepsy

    • Parent with onset of epilepsy BEFORE the age of 20 years, risk of epilepsy in children:
      • 2.3%-6%
    • Parent with onset of epilepsy AFTERthe age of 20 years, risk of epilepsy in children
      • 1%-3.6%

  • If a person has epilepsy, his or her sibling (brother or sister) is at higher risk of developing epilepsy. The younger the age of onset of epilepsy, the higher the risk that the sibling will develop epilepsy.

    • If  a patient develops epilepsy starting at age 0-9 years, the risk that the brother or sister will develop epilepsy:
      • 9.5%
    • If  a patient develops epilepsy starting at age 10-24 years, the risk that the brother or sister will develop epilepsy
      • 5.8%
    • If  a patient develops epilepsy starting after the age of 35 years, the risk that the brother or sister will develop epilepsy:
      • No increased risk

CHROMOSOME DISORDERS CONSISTENTLY ASSOCIATED WITH EPILEPSY

Some genetic neurologic conditions have seizures as a feature of their disorder. This may occur in all or nearly all patients with the genetic abnormality. It should be noted- these conditions are uncommon. Most patients with epilepsy do not have a specific chromosomal abnormality that the clinician can point to. The following is a list of two examples of chromosomal disorders in which patients typically develop seizures:

  • Angelman Syndrome: Patients with this disorder have an abnormal chromosome 15. Patients have severe learning disabilities, tremor and poor coordination. The patient’s often have a happy appearance- they tend to smile and frequently laugh. Over 80% of patients will develop epilepsy.
  • Ring Chromosome 20 Syndrome: Any person’s chromosomes can be looked at- with all the patients chromosomes laid out for analysis. The total number of chromosomes in a normal person is 46 chromosomes. The chromosomes can be laid out and a picture taken. If you have ever seen a chromosome picture, the chromosome looks like a little worm or a match stick. For patients with Ring Chromosome 20 Syndrome, chromosome 20 looks like a ring—instead of a straight stick, the chromosome has curled into a ring shape. This is abnormal. Patients with this disorder have poor concentration, impulsive behavior and sleep problems. Essentially all patients develop epilepsy at some point. Seizures usually occur out of sleep. Seizures are often associated with hallucinations.

COMPLEX  EPILEPSIES

Some patients, as noted in the above section, can have a single chromosome abnormality that can be clearly tested for and identified.  The single chromosome abnormality causes the neurologic disorder and epilepsy. This is (relatively!) straight forward. This is also relatively rare. A much more common scenario is that genetics plays a role in a patient developing epilepsy, but the cause and effect nature is not clearly understood and may be very complex. For example, some patients may have multiple genes that are abnormal, and it is the combination of these abnormalities that result in the epilepsy.

Let’s use mild head trauma as an example to help clarify some of these issues. Have you ever wondered why some people with mild head trauma develop epilepsy and some people do not? It is possible that there are people in the world who carry genes that predispose them to have seizures. But they may never develop epilepsy unless something happens to trigger the seizure activity. In our example, a person may have never developed epilepsy until he or she had the mild head trauma. Thus, it could be the combination of the genes and the mild head trauma that results in the epilepsy. If you could analyze 100 people who had the exact same mild head trauma, some of these patients may go on to develop epilepsy. The reason that some people develop epilepsy and some do not- may be related to differences in their genes!

(Please note: for many people, genetics may play only a minor role or no role whatsoever in their epilepsy. For example, people with head trauma may have no genetic predisposition to epilepsy. The trauma causes scarring in the brain and that is the whole cause of the epilepsy. The main point I want to make is that genetics may play a role in some patient’s epilepsy that may be surprising. The old thinking was that an injury to the brain like head trauma was the entire explanation for the cause of the epilepsy—and genetics had nothing to do with the seizures. The new thinking- genetics may play a role in some patients, even in cases of brain injury. This may be true even in adults.  As is often the case, the full story can be complicated!).

CONCLUSIONS

The information on genetics and epilepsy is progressing at a rapid pace. The research is absolutely fascinating!

If readers would like more information on this topic, let me know. For example, more information on the basics of genetics, DNA etc. Also, additional information on what genes to test for in patients with epilepsy may also be of interest.

References

Elmslie F. Genetic Counseling. In: Engel J, Pedley T, ed. Epilepsy: A comprehensive Textbook. Philadelphia: Lippincott Williams &Wilkins 2008: p. 211-215.

Goldman AM. Genes, seizures and epilepsy. Epilepsy.com

http://www.epilepsy.com/pdfs/Except_parent_art4.pdf

Zuberi S. Chromosome Disorders Associated with epileptic seizures. In: Panayiotopoulos CP, ed. Atlas of Epilepsies. London: Springer 2010: p. 121-127.

Dr. White has been practicing as a full-time epileptologist since 1999. His practice focuses on optimizing the diagnosis and treatment of patients with seizure disorders. Dr. White’s special interests include patient education, improving the side-effect profile of seizure medications, and epilepsy surgery.

15 Responses to “Facts on Genetics and Epilepsy”

  1. Hi Dr. White,
    I had my first grand mal seizure at 15 and was diagnosed with epilepsy six months later when I had a second one at which point I was put on Tegretol. Until I was 26 I was having about two seizures per year. The frequency started increasing, going to about every six weeks, so my doctor switched me to Lamictal and I now have about one per year. A little history, I am 31 now and have one cousin on my fathers side who had seizures in her late teens but they stopped. I also had two concussions before the age of seven. I have never had a seizure outside of my bed in the morning and right after I wake up. Never had one during the day or night.
    I always thought I wouldn’t have children because I didn’t think it safe or fair to possibly pass this on. I’ve been reading more about it though and I’m starting to think it might be possible. One question I have about your findings is the increased chances based on age of onset. You say 2.3-6% more if onset was under age 20. Is that on top of the 2.9-8.7? I was also wondering how you feel about ketogenic diets?
    Many thanks,
    Amanda Howard

  2. One more thing, if I go to a geneticist, what kinds of questions should I ask and what tests should be performed?
    Thanks, Amanda

  3. Great article. My brother and I are both epileptic. It’s been difficult getting solid answers on the probability of this and the potential causes, as we are the first recorded epileptics in our family. I understand the knowledge on epilepsy is relatively new and still in it’s developmental stages. However, it’s comforting to know at least a little more about my disorder.
    Thank you!

  4. I’m just curious and have one question. I’ve had 13 surgeries on my ears, between having tubes put in and reconstructive surgery on my right ear drum, now I later developed epilepsy, nobody else in my entire family has it. is there anyway that I could’ve developed epilepsy from so many surgeries ?

  5. Hello my friends family dont have epilepsy history at all.
    she is 24 and at in her child hood she had fever and then her eyes rolled out for some time,but thats it,after that she never had anything regarding that,
    Her younger sister is 15 years old and before 2 years she had first seizure(we have reports) then she started medicines and after 2 years now she had next seizure(stroke/fit) and doctor changed her medicines,
    now my question is
    1)will my friend develope epilepsy?
    2)if she get married with boy with no epilepsy history will her children has more risk of epilepsy?
    3)I think she should get genetic test done,?,,so that she should know is it in her genese? to develope the epilepsy.
    4)Lets say her children will not get any epilepsy,but as its genetic,,it will surely come somewhere in next generations? or will it eliminate ?
    5)Is there any procedure to by which we can predict and eliminate epilepsy before birth?
    6)Should she tell any person about her sister ,before marriage,will it affect relations?

  6. If parents dont have epileptic history ,
    And they have 2 daughters
    One is 25 year old and other is 13,,
    The younger girl just developed generalised epilepsy at thr age of 13,,
    How are the chances of elder sister(25)will develop epilepsy,,or her childrens eill be at risk?
    Please also mail your answer to
    roymalhotra08@yahoo.co.in

  7. I was wondering if someone is told they have black spots in there CT on there brain yet the person is also told that they have epilepsy could those spot have been caused by head trauma? I am just lost in this whole thing and advice would help.

  8. I have epilepsy. I just turned 28, and have no children. One day I would like to have kids possibly, but I certainly don’t want them to be afflicted with epilepsy. When I was diagnosed, they said I was born with epilepsy but it didn’t surface until I was 16 in the form of PETITE-MAL seizures. By the time I was 20, I had started having GRAND- MAL seizures. I’ve had VNS surgery, and I take so many medicines… I can’t imagine putting someone else through that. If I were to eventually have children, is there any possibility that they would not have epilepsy? Or would I have to take a preventative medicine to protect the baby?

  9. Both my children one onset at 4 and one onset at 13 have epilepsy. No trauma, no family history, and the younger child male had his seizure first. Seems odd that both my children would have this…any suggestions to understand why.

  10. Bernadette McCarthy December 21, 2015 at 9:12 am

    Hello. My son was diagnosed epileptic at 5yrs after he fell unconscious and unresponsive in the car. Initially diagnosed with generalized seizures mostly drop seizures and zone out episodes.He is now 7 and has developed grand mal seizures at night. He takes Trileptal. Thomas was also born with Trisomy 21. At 2 he began Thyroxine for under-active thyroid and at 5 he developed Graves Disease and takes Carbimazole. He is now 7. We are told Tom may have had epilepsy from birth or it developed and it is more likely due to his Trisomy 21. Tom has a brother who is 5 and he has started to have similar jerky movements at night and trouble getting to sleep. Is it possible he could also have or develop epilepsy. We are not aware of any other family history of epilepsy. Given that we didn’t notice seizure activity until we looked for it after diagnosis, should we be concerned? BM

  11. Can you discuss the chances of two epileptic parents, with or without known genetic predisposition, passing epilepsy onto their children? Please do not publish my full name as I am attempting to create and retain a web presence. Thank you.

  12. Both my children one onset at 4 and one onset at 13 have epilepsy. No trauma, no family history, and the younger child male had his seizure first. Seems odd that both my children would have this…any suggestions to understand why.

    My 14 year old also has bilateral hip dysplasia.

    • Hi Wendy,
      I happened upon your story while researching siblings with epilepsy. My story is shockingly similar to yours! I have 3 daughters, two of which have epilepsy. The youngest daughter developed epilepsy first at the age of 4, and my oldest daughter recently at the age of 14. Still in the very stages of diagnosis with my oldest, and really there aren’t too many correlations between the girls’ epilepsy. I am very curious about what you have since learned regarding your children’s cases and if you have information that may be helpful to me and my babies. Any recommendations or advise is welcome Thank you for sharing your story!

      Rheta Melvin

  13. we dont have history of epilepsy in my family. nither in my fathers family nor my mothers family. my parents never had this kind of problem. even we 5 sublings also never had epilepsy . but my 2 sisters sons had epilepsy . my elder sisters both sons (1st one started at age of 6 and 2nd son on age of 7) and youngers sisters one son ( age of 24) is suffering for the same.what the reson ?

  14. Dr White,

    Now over 50 lengthy history of febrile convulsion age 4, then absence seizures diagnosis up to 100 or more a day, then eyelid myoclonia (Jeavons) early teens, then tonic-clonics at 17 yrs, then eyelid myoclonia absence status epilepticus. No family history of any epilepsy. Now have 3 children, 1 child had early absence seizures and has outgrown it, the 2nd child has early absence seizures diagnosis but has the Jeavons still taking medication and the 3rd child (1st born) has nothing, how is this possible to have no family history in my generation or ancestry generations but now have a family epilepsy syndromes (generalised)?

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