Genetyczne powiązania między autyzmem a epilepsją: od mechanizmów molekularnych do spersonalizowanego leczenia
Genetic Convergence of Autism Spectrum Disorder and Epilepsy: From Molecular Mechanisms to Precision Therapeutics
W skrócie
Autyzm i epilepsja często występują razem u tej samej osoby, szczególnie u osób z niepełnosprawnością intelektualną. Badania genetyczne wykazały, że obie choroby mają wspólne przyczyny na poziomie genów, których zaburzenia wpływają na pracę mózgu, przewodnictwo impulsów nerwowych i tworzenie połączeń między neuronami. Choć czasami napady padaczkowe pogorszają objawy autyzmu, nie zawsze istnieje bezpośrednia związek przyczynowy między tymi schorzeniami, dlatego leczenie musi być dostosowane do konkretnego genu pacjenta i może obejmować leki działające na kanały jonowe, terapie genowe lub zmianę metabolizmu.
Oryginalny abstract (angielski)
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 , , , , , , , and . 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.