Genetic Testing Rarely Found Causes Before Epilepsy Surgery

What was studied

This study looked at how often genetic testing finds a clear epilepsy-related cause in adults being evaluated for epilepsy surgery. The researchers included 115 adults in the Calgary Epilepsy Program from 2019 to 2023 who had research exome sequencing.

They applied a panel of 765 genes linked to epilepsy and used standard rules to classify whether genetic changes were pathogenic or likely pathogenic. They also assessed clinical relevance and possible association with surgery outcomes.

What they found

Pathogenic or likely pathogenic genetic variants were found in 4 of 115 adults, a diagnostic yield of 3.5%. The variants were in DEPDC5, NPRL2, KCNT2, and PRRT2. None of these patients had intellectual disability, and only one of the four had a positive family history. Three of the four did not have features that would have prompted clinical genetic testing, according to the authors. One person with a KCNT2 variant had epilepsy surgery and had a good outcome after surgery.

Limits of the evidence

This was a single-center cohort of 115 adults, so the results may not apply to all epilepsy surgery programs. The study was based on research exome sequencing and a selected gene panel, so results could differ with other testing methods or in other groups. Only 4 people had pathogenic or likely pathogenic findings, which limits conclusions about which patients should be tested or how genetic results relate to surgery outcomes. The study reports diagnostic yield in this group, but it does not establish whether testing improves care or surgery results.

For families and caregivers

For families, this study suggests that genetic testing before epilepsy surgery in adults had a low diagnostic yield in this group. At the same time, some people with pathogenic or likely pathogenic findings did not have the usual features that might prompt clinical genetic testing, so these diagnoses might otherwise have been missed. This may be worth discussing with an epilepsy specialist when considering whether genetic testing should be part of a surgery evaluation.

What to watch next

Larger studies across multiple centers could help clarify diagnostic yield in different settings and whether genetic findings are associated with treatment decisions or surgery outcomes.

Terms in this summary

diagnostic yield

How often a test finds a clear answer or diagnosis.

presurgical evaluation

The testing and review done before deciding whether epilepsy surgery may help.

exome sequencing

A genetic test that looks at the parts of genes that contain instructions for making proteins.

variant

A change in DNA; some variants are harmless, while others can cause disease.

pathogenic

Disease-causing.

gene panel

A selected group of genes checked for changes linked to a condition.

intellectual disability

A condition with limits in learning and everyday thinking skills that starts during development.

family history

Whether close relatives have had the same or related health problems.