Genetic testing in children enrolled in epilepsy surgery program. A real-life study

Area of Science:

• Neuroscience
• Genetics
• Pediatric Neurology

Background:

• Limited comprehensive analyses exist for genetic diagnoses in pediatric epilepsy surgery evaluations.
• Understanding genetic etiologies is crucial for drug-resistant epilepsy and malformations of cortical development (MCD).

Purpose of the Study:

• To analyze genetic diagnoses in children undergoing pre-surgical evaluation for epilepsy.
• To investigate the impact of genetic findings on surgical outcomes and strategy.

Main Methods:

• Prospective cohort study of children in an epilepsy surgery program (Jan 2018-July 2022).
• Germline and/or somatic genetic testing performed on the majority of patients.
• Analysis of predictors for surgical outcome and positive germline genetic testing results.

Main Results:

• Germline genetic diagnosis identified in 13/74 patients (variants in CHRNA4, NPRL3, DEPDC5, etc.) and three copy number variants.
• Somatic gene testing detected 10 pathogenic/likely pathogenic variants (SLC35A2, PTEN, MTOR, etc.).
• Germline genetic diagnosis was significantly associated with focal epilepsy of unknown onset.

Conclusions:

• Germline and somatic genetic testing provide definitive diagnoses in a substantial subgroup of epilepsy surgery patients.
• While genetic diagnosis can influence surgical decisions, selected patients with genetic focal epilepsies and MCD may still benefit from resective surgery.
• Genetic diagnosis does not preclude patients from pre-surgical evaluation and surgical intervention.