Genetic Convergence of Autism Spectrum Disorder and Epilepsy: From Molecular Mechanisms to Precision Therapeutics.
- 1Department of Pediatrics, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria.
- 2University Hospital "St. George", 4000 Plovdiv, Bulgaria.
Abstract
Autism spectrum disorder (ASD) and epilepsy frequently co-occur, with the clinical overlap particularly evident in individuals with intellectual disability, developmental impairment, and genetically defined neurodevelopmental disorders. Advances in genomic diagnostics have revealed substantial genetic and molecular convergence between ASD and epilepsy. This convergence encompasses both recurrent copy-number variants (CNVs), including 15q11-q13, 16p11.2, and 22q11.2 rearrangements, and sequence-level alterations in genes implicated in both epilepsy and ASD-related neurodevelopmental phenotypes, including SCN1A, SCN2A, GRIN2A, SYNGAP1, STXBP1, TSC1/TSC2, MECP2, and UBE3A. These diverse genetic alterations affect gene dosage, ion-channel function, synaptic organization and neurotransmission, intracellular signaling, and gene regulation, ultimately converging on disruption of circuit homeostasis, excitation-inhibition regulation, synaptic plasticity, and network dynamics. Importantly, the relationship between epilepsy and ASD is neither uniform nor necessarily causal: epileptic activity may aggravate neurodevelopmental dysfunction in some disorders, whereas in others, seizures and autistic features represent partially independent consequences of a shared genetic defect. This heterogeneity has major therapeutic implications. Emerging precision approaches increasingly incorporate variant-specific functional effects and include ion-channel modulation, pathway-directed treatments, metabolic correction, and gene- or RNA-targeted therapies. However, successful seizure control does not necessarily translate into normalization of neurodevelopmental outcomes, emphasizing the importance of developmental timing and of distinguishing seizure-directed benefit from modification of the underlying neurodevelopmental disorder. This review integrates clinical, genetic, molecular, cellular, and network-level evidence linking ASD and epilepsy and examines how these convergent mechanisms may guide precision therapeutics and future early-intervention strategies.
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BibTeX
@article{pacheva2026genetic,
title = {{Genetic Convergence of Autism Spectrum Disorder and Epilepsy: From Molecular Mechanisms to Precision Therapeutics.}},
author = {Iliyana Pacheva},
journal = {Genes},
year = {2026},
month = oct,
doi = {10.3390/genes17101308},
url = {https://europepmc.org/article/MED/42938424},
note = {CC BY},
}
RIS
TY - JOUR
TI - Genetic Convergence of Autism Spectrum Disorder and Epilepsy: From Molecular Mechanisms to Precision Therapeutics.
AU - Iliyana Pacheva
PY - 2026
DA - 2026/10/20
JO - Genes
DO - 10.3390/genes17101308
UR - https://europepmc.org/article/MED/42938424
AB - Autism spectrum disorder (ASD) and epilepsy frequently co-occur, with the clinical overlap particularly evident in individuals with intellectual disability, developmental impairment, and genetically defined neurodevelopmental disorders. Advances in genomic diagnostics have revealed substantial genetic and molecular convergence between ASD and epilepsy. This convergence encompasses both recurrent copy-number variants (CNVs), including 15q11-q13, 16p11.2, and 22q11.2 rearrangements, and sequence-level alterations in genes implicated in both epilepsy and ASD-related neurodevelopmental phenotypes, including SCN1A, SCN2A, GRIN2A, SYNGAP1, STXBP1, TSC1/TSC2, MECP2, and UBE3A. These diverse genetic alterations affect gene dosage, ion-channel function, synaptic organization and neurotransmission, intracellular signaling, and gene regulation, ultimately converging on disruption of circuit homeostasis, excitation-inhibition regulation, synaptic plasticity, and network dynamics. Importantly, the relationship between epilepsy and ASD is neither uniform nor necessarily causal: epileptic activity may aggravate neurodevelopmental dysfunction in some disorders, whereas in others, seizures and autistic features represent partially independent consequences of a shared genetic defect. This heterogeneity has major therapeutic implications. Emerging precision approaches increasingly incorporate variant-specific functional effects and include ion-channel modulation, pathway-directed treatments, metabolic correction, and gene- or RNA-targeted therapies. However, successful seizure control does not necessarily translate into normalization of neurodevelopmental outcomes, emphasizing the importance of developmental timing and of distinguishing seizure-directed benefit from modification of the underlying neurodevelopmental disorder. This review integrates clinical, genetic, molecular, cellular, and network-level evidence linking ASD and epilepsy and examines how these convergent mechanisms may guide precision therapeutics and future early-intervention strategies.
SN - 2073-4425
ER -