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Updated: Jan 25, 2026

Author Spotlight: Advancing Pediatric Epilepsy Surgery in Children Through Novel Biomarkers and Enhanced Localization
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Executive functioning in children with epilepsy: Genes matter.

Chiara Colliva1, Marta Ferrari2, Cristina Benatti3

  • 1Dept. of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Epilepsy & Behavior : E&B
|May 5, 2019
PubMed
Summary

Genetic factors like MTHFR and COMT gene variations influence executive functions (EF) in children with epilepsy. These genetic predispositions may explain cognitive variability and inform personalized care strategies.

Keywords:
COMT Val158MetEpilepsyExecutive functionGene vulnerabilityInterindividual variabilityMTHFR C677T neurodevelopment

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Area of Science:

  • Neuroscience
  • Genetics
  • Pediatric Neurology

Background:

  • Pediatric epilepsy presents a variable cognitive and behavioral phenotype, including executive functioning (EF) and attention deficits.
  • Interindividual variability in neurocognitive outcomes among children with epilepsy is significant and not fully understood.
  • Genetic factors influencing brain development and neurotransmitter systems are implicated in this variability.

Purpose of the Study:

  • To investigate the interaction between MTHFR C677T and COMT Val158Met gene polymorphisms in children with epilepsy.
  • To determine if allelic variations in these genes are associated with variability in cognitive phenotypes, particularly executive function.
  • To explore the role of methylation and dopamine availability in the prefrontal cortex (PFC) related EF.

Main Methods:

  • Studied 42 children aged 5-12 years with epilepsy.
  • Assessed executive function through direct testing and parent-rated indirect measures.
  • Genotyped MTHFR C677T and COMT Val158Met polymorphisms.

Main Results:

  • MTHFR T allele carriers showed poorer indirect EF compared to CC carriers.
  • A significant decline in indirect EF, especially working memory, was noted in T allele carriers with at least one COMT met allele.
  • Direct EF was compromised in COMT Val/Val carriers, suggesting reduced dopamine availability increases risk for attention and planning deficits.

Conclusions:

  • Genetic variations in MTHFR and COMT genes significantly impact PFC-related executive functions in children with epilepsy.
  • Methylation and dopamine availability are key genetic factors contributing to cognitive phenotype variability.
  • Genetic vulnerability should be considered a polygenic risk, informing personalized patient profiles and care from diagnosis.