DNA test

Why is genetic testing for epilepsy important?

genes and the brain
Source: National Human
Genome Research Institute
  • Genetic testing may help identify the cause of a person's epilepsy.
  • It may lead to an accurate diagnosis and the best possible medical management.
  • It may be particularly helpful for individuals with genetic epilepsy disorders whose seizures are not well-controlled.

In some cases, a genetic diagnosis may help guide the selection of anti-seizure medications, as there are some known links between certain medications and genetic epilepsy disorders. For example, there is evidence that some medications may work better to control seizures in people with a genetic diagnosis. There is also evidence that some medications may not work well or cause adverse side-effects in people with other types of genetic epilepsies1-3.

In certain cases, a genetic diagnosis may also help to obtain information about long-term outcome. For example,

  • For some genetic epilepsies, seizures may be expected to stop at a certain age, meaning that his or her doctor may decide it is safe to stop anti-seizure medication4-5.
  • Results of genetic testing may help better inform family members of their own risk of epilepsy, as well as their chances of having a child with epilepsy.
  • Having a genetic diagnosis may also make it possible for individuals and families to access other resources. These include support from advocacy groups and peer families.
  • It may help lead to participating in research studies specific to the genetic diagnosis.
  • Obtaining a diagnosis may help an individual or family end what is often referred to as the “diagnostic odyssey” or the search for an answer.

Webinar Recording on "Epilepsy and Genetics: The Basics"

Topics Included

  • What are the benefits and limitations of testing?
  • What genetic tests are available for people with epilepsy?
  • How do I go about getting testing and insurance coverage?
Recorded January 22, 2020

Types of Genetic Testing

There are many types of genetic tests. Some tests focus on

  • Individual genes
  • Groups of genes
  • Chromosomes
There is no single test that can diagnose all genetic epilepsies.
Holly Patrick MS MPH of CDC
Credit: CDC - Holly Patrick MS, MPH

Because there is no single test that can diagnose all genetic epilepsies, multiple tests may be recommended. Often, testing may be done one after another. Many laboratories offer genetic testing for the epilepsies and there is considerable variation from laboratory to laboratory. For all of these reasons, it is important that a healthcare provider who is knowledgeable about genetic testing be involved in the process.

What are the most common genetic tests for epilepsy?

Common examples of genetic tests for epilepsy include the following.

Epilepsy Gene Panel

  • This test involves the analysis of the most common genes associated with epilepsy.
  • There are many types of epilepsy gene panels.
  • Some have fewer than 20 genes and others have many hundreds of genes.

Chromosome Microarray

  • This genetic test involves analysis of a person’s chromosomes (structures that contain DNA).
  • Checks to make sure there are no imbalances that could cause epilepsy. Imbalances include extra or missing pieces of chromosomes – or – extra or missing entire chromosomes.

Whole Exome Sequencing

  • This complex genetic test involves analysis of the entire DNA code to look for changes in genes associated with epilepsy.
  • It is similar to the epilepsy gene panel, but looks at a much larger number of genes, including rare and newly discovered genes.

Targeted Testing

  • If there is already a known genetic cause of epilepsy in a person, other family members may have targeted testing to help clarify their risk.

How is genetic testing for epilepsy performed?

genes and cells
Source: National Human
Genome Research Institute
  • Most genetic tests are performed using DNA extracted from a blood sample.
  • In some cases, a saliva sample or cheek swab sample may be used.
  • Less frequently, a skin biopsy may be needed.

Will insurance cover the cost of testing?

  • Each individual insurance plan has its own rules regarding the coverage of genetic tests.
  • Most plans require pre-approval or prior authorization before testing.
  • Doctors and genetic counselors who order genetic tests can help explain insurance coverage and the cost of the testing.
  • Some insurance companies require genetic counseling before providing coverage for a genetic test.

A Note on Insurance

scale of justice
 

There is a federal law called the Genetic Information Non-discrimination Act (GINA). Enacted in 2008, this law provides some protection against discrimination based on genetic information. This legislation is limited, applying only to some health insurance providers and to employers. It does not extend to life insurance or long-term care insurance providers.

Here are some helpful websites to learn more:

What kinds of results can I expect from genetic testing?

gene sequencing
Source: National Human
Genome Research Institute

Genetic testing may provide diagnostic information regarding a person’s risk of having a genetic epilepsy disorder.

Positive Test Result

  • For a person with epilepsy, a positive result means that a genetic change has been identified as the cause of his or her epilepsy diagnosis.
  • A positive result in an otherwise healthy individual could indicate that person is at risk for epilepsy.
  • Genetic testing may also give information about reproductive risks and can help clarify if and how epilepsy is inherited in a family.

Negative Test Result

  • A negative test result in a person with epilepsy means that a genetic cause of epilepsy was not identified using the test that was performed.
  • A negative result does not completely rule out the possibility of a genetic diagnosis.
  • In some cases, more testing may be considered.

Uncertain Test Result

  • It is also possible to receive uncertain results from a genetic test.
  • An uncertain result means that a genetic finding was detected, but the meaning of the finding is not known.
  • These results are referred to as genetic variants of uncertain significance (VUS). A VUS result may be re-interpreted at a later date when more information becomes available and could end up being re-classified as either benign (negative) or pathogenic (disease causing/positive).

Will genetic testing help me and my doctor choose the best treatment?

precision medicine
Source: National Human
Genome Research Institute

In some instances, genetic test results play a role in finding the right medical care for a person with epilepsy. Results may help doctors select the best treatment option (such as the most effective anti-seizure medication) and determine the need for additional evaluations or services. However, at this time, most genetic epilepsies do not yet have a targeted treatment. Being able to identify precision (exact and best) treatments based on genetic diagnosis is a major focus of research efforts. It is likely in the future that this will become more frequent.

Should every person with epilepsy have genetic testing?

If a person has epilepsy due to a known cause (such as a brain injury), genetic testing is not likely to reveal helpful information. Genetic testing may be considered for anyone with epilepsy when there is not a known cause.

Testing is more likely to identify a genetic diagnosis if the individual has

  • Refractory (difficult to treat) epilepsy
  • Other significant neurodevelopmental or neurological symptoms (such as developmental delay, autism spectrum disorder, or movement disorder)
  • A strong family history of epilepsy
Genetic testing may be considered for anyone with epilepsy when there is not a known cause.

Genetic testing is not for everyone.

  • Choosing to have a genetic test is a personal decision that should be made with the help of a medical professional.
  • Results of a genetic test may have many implications for an individual and their family members. These include medical, reproductive, psychological, and financial implications.
  • It is important to consider these factors when deciding to get genetic testing.
  • Some people may choose not to pursue testing for these reasons.

Do my family members need to be tested?

A positive result on a genetic test may impact family members. Typically, testing may initially be extended to first-degree relatives (parent or sibling). Depending on their results, more distant family members may benefit from testing as well.

Whether or not testing is recommended for family members depends on many factors, most importantly the specific genetic diagnosis and the inheritance pattern (how conditions are passed on). Individuals and families should seek guidance from a medical geneticist or genetic counselor to find out if testing of family members is important.

References

  1. Wang D, et al. Glucose Transporter Type 1 Deficiency Syndrome. GeneReviews. March 2018.
  2. Wirrell EC. Treatment of Dravet Syndrome. Can J Neurol Sci, 2016. 43 Suppl 3: p. S13-8.
  3. Saneto RP, et al. POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders. Seizure, 2010. 19(3): p. 140-6.
  4. Miceli F, et al. KCNQ2-Related Disorders. GeneReviews. Sept. 2018.
  5. Berkovic SF, et al. Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy. Ann Neurol, 2004. 55(4): p. 550-7.
Authored By: 
Antonina Wojcik MS, CGC
Authored Date: 
12/2019
Reviewed By: 
Annapurna Poduri MD, MPH
Beth Rosen Sheidley MS, CGC
Elaine Kiriakopoulos MD, MSc
Elaine Wirrell MD
Epilepsy Foundation Digital Strategies & Engagement
on: 
Thursday, April 23, 2020