Facts on Genetics and Epilepsy

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 AFTER the 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.

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.