Pediatric Epilepsy: Insights from Genetics to Mechanisms

Dear Colleagues,

Pediatric epilepsy (PE) comprises a heterogeneous group of disorders characterized by recurrent, unprovoked seizures with onset in infancy or childhood, often resistant to standard anti-epileptic drugs. Over the past two decades, advances in genomics and next-generation sequencing have significantly expanded our understanding of the molecular basis of PE, leading to the identification of numerous causative or contributory genes involved in synaptic transmission, ion channel function, and cortical development—typically through de novo or inherited mutations. Complementary multi-omics approaches have further illuminated the complex genetic architecture of PE, uncovering key molecular pathways involved in its pathogenesis. Despite these advances, significant challenges remain in translating genetic findings into biological insight and clinical impact. Many variants still lack functional validation, and crucial mechanisms—such as those involving neuronal transmission, neuron–microglia interaction, and cell-type-specific gene expression—are only beginning to be unraveled.

                In parallel, patient-derived induced pluripotent stem cells (iPSCs), brain organoids, and in vivo models have opened new avenues for studying PE-related mechanisms in physiologically relevant systems. These models allow researchers to investigate how genetic alterations lead to neuronal network dysfunction and to assess targeted therapies in preclinical contexts. In addition, emerging technologies such as single-cell and spatial transcriptomics are revealing the cellular heterogeneity and spatial organization of brain development in both health and disease. This area of research is critically important—not only for advancing our understanding of the biological basis of PE, but also for driving the development of effective therapeutic strategies. Ultimately, the integration of genomic discovery, functional modeling, and translational research holds great promise for bridging the gap between bench and bedside, with the goal of improving outcomes for affected children.

                We are pleased to invite you to publish high-quality research on the genetic and molecular basis of PEs, with particular emphasis on multi-omics technologies and translational approaches. The issue will showcase recent advances in gene discovery, variant validation, transcriptomic and epigenetic profiling, sex-specific mechanisms of epileptogenesis, disease modeling using iPSCs and brain organoids, and innovative therapeutic strategies. We welcome both original research and reviews. Our goal is to compile at least 10 articles—with full editorial support—and, if reached, the issue may also be printed in book form. This collection will appeal broadly to researchers in genetics, molecular biology, neuroscience, and translational medicine.

Research areas may include (but are not limited to) the following:

• Advances in diagnostic technologies and functional genomics;
• Identification of novel PE-associated genes;
• Functional validation of genetic variants;
• Single-cell and spatial transcriptomics in brain development and disease;
• Modeling PE using patient-derived iPSCs and brain organoids;
• Neuron–microglia communication in PE systems;
• Sex differences in genetic and molecular pathogenesis of PEs;
• Novel therapeutic approaches (including gene therapy, small molecules, and cannabinoids) and preclinical testing.

We look forward to hearing from you.

Dr. Denise Drongitis
Dr. Maria Giuseppina Miano
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• integrative omics
• organoid models
• brain development
• PE-related pathways
• innovative therapeutic approaches