Diagnostic Yield of Reanalysis After Nondiagnostic Genome Sequencing in Infants With Unexplained Epilepsy

Dr. Halley Alexander and Dr. Alissa M. D'Gama discuss genetic testing for infantile epilepsies.

Show citation:

Nguyen JNH, Lachgar-Ruiz M, Higginbotham EJ, et al. Diagnostic Yield of Comprehensive Reanalysis After Nondiagnostic Short-Read Genome Sequencing in Infants With Unexplained Epilepsy. Neurology. 2026;106(6):e214645. doi:10.1212/WNL.0000000000214645

Show transcript:

Dr. Halley Alexander:

Hi, this is Halley Alexander with today's Neurology Minute, and I'm here with Dr. Alissa D'Gama from Boston Children's Hospital and Harvard Medical School, and we just finished recording a full-length podcast about some exciting new work in genetic testing for infantile onset epilepsies. Alissa, can you tell us what you found briefly and why it's important for neurology care?

Dr. Alissa D'Gama:

Infantile epilepsies are relatively common, and they're associated with substantial burden of disease, and we know that identifying underlying genetic causes can impact clinical care. It's important for emerging precision therapies. But even after genome sequencing, which is the most comprehensive clinical genetic testing currently available, most infants remain genetically unsolved.

And so what we did was take that genome sequencing data and reanalyze it for a cohort of infants who had unexplained non-acquired epilepsy and non-diagnostic genome sequencing, and in about 5% of cases, our reanalysis was able to identify a genetic diagnosis, and all of these diagnoses had impact on clinical care for their infants and their families. In some cases, we could incorporate new information, either new clinical information about the patient or new scientific methods or information about disease associations, and in other cases, we were able to incorporate new analysis methods to identify variants. And so our findings suggest that implementing reanalysis for infants or any individual with epilepsy within a year or two of non-diagnostic testing may be useful.

Dr. Halley Alexander:

Thank you so much, and you can find a lot more details by listening to the full-length podcast, which is available now on the Neurology podcast, and you can find the full article in the March 10th issue of Neurology or online at neurology.org. As always, thanks for tuning in for today's Neurology Minute.