Unexplained epilepsy doesn’t have to remain unexplained. Even for adults, answers are within reach.

It’s quickly becoming the standard of care to order genetic testing for pediatric patients with unexplained epilepsy and help families get answers early. However, it’s a relatively recent shift, and thousands of adults with unexplained epilepsy still live with uncertainty of the root cause of their seizures. That’s because many adults with epilepsy received their clinical diagnosis years ago, when genetic testing options were more limited.

Ten to twenty years ago, the standard pediatric epilepsy work-up would have included clinical testing, including EEG and brain imaging. Some individuals may have been offered genetic testing in the form of a microarray, single-gene testing or a small gene panel, if any genetic testing at all.²

That means a significant number of adult patients are missing out on answers—and potentially missing out on reductions in seizures or side effects that they might benefit from if they had a genetic diagnosis and updated medical management.

Answers that can inform treatment

The numbers speak for themselves:

~50% of unexplained epilepsy cases have a genetic cause,¹

More than half of diagnostic findings are clinically actionable,³ with patients experiencing up to 90% seizure reduction in some cases.⁴

That’s because therapies, clinical trials, and management strategies for genetic epilepsies have expanded in recent years.

Even into a patient’s later years, a genetic diagnosis can help guide a more tailored management approach and treatment changes—decreasing seizures and identifying contraindicated medications. This can result in improvements in:

seizure frequency

cognition

language and communication

quality of life¹

Many of your adult patients could already be candidates for therapies they’ve never had the chance to try. Just a few examples:

For patients with SCN1A variants, a genetic diagnosis often means fewer seizures, fewer side effects, and a chance at a more normal life. More than half of patients with a genetic variant in SCN1A had a decrease in seizure frequency after treatment changes enabled by their genetic diagnosis.⁵

For patients with CDKL5 deficiency disorder, options were once limited. Now, a new neuroactive steroid has been developed specifically for patients with CDKL5, which has been shown to decrease seizures.⁶

Several gene therapies for epilepsy are entering clinical trials; these investigational treatments may offer an alternative to drug and surgical therapies, and show potential for precise and personalized care.^7,8

Even in cases where seizure control isn’t fully possible, knowing the genetic cause of a patient’s epilepsy can still prevent unnecessary or harmful treatments, open doors to supportive therapies and community resources, and provide emotional relief and a sense of closure.

Yet most adult epilepsy patients have never received comprehensive genomic sequencing.

When panel testing isn’t enough

Even if your patient received a test like a panel or chromosomal microarray (CMA) in the past, it may have missed a genetic diagnosis, as these tests are much more limited.

Now we know that epilepsy can be caused by changes in more than 900 genes⁸—and we expect more to still be discovered.

Today’s exome sequencing can analyze thousands of genes in one test, covering both known and newly discovered epilepsy genes. That’s a big step forward from panel tests, which are limited to looking at just a set number of genes.

In a recent study, six commercially available epilepsy panels:⁵

Did not include 57% of seizure-related genes
Would not have returned a positive result for the majority of patients who received a genetic diagnosis with exome sequencing

Exome sequencing: More likely to provide a genetic diagnosis

Diagnostic yield of exome sequencing in patients >18 years³

Exome sequencing finds a genetic variant for 1 in 4 adult patients with epilepsy⁵—making it more likely to find the root cause than other types of genetic testing.

Recommended as a first-line test for unexplained epilepsy

The National Society of Genetic Counselors (NSGC) recommends exome sequencing as a first-tier test for all individuals with unexplained epilepsy, regardless of age or comorbidities.⁹ This recommendation is endorsed by the American Epilepsy Society (AES).

More accessible than ever

Exome sequencing is now within reach for most patients, with more insurers recognizing its value. As a neurologist, you can help your adult patients finally get the clarity they’ve missed.

As the leading genomic testing brand amongst healthcare professionals for exome sequencing, GeneDx is here to help. Our testing aligns with the NSGC recommendation and AES endorsement—and our team is here to help you interpret results and plan next steps with confidence.

Plus, more patients are covered than you may think. Many insurance companies now recognize the importance of exome sequencing for patients with epilepsy, and their coverage policies reflect that understanding.