Genetics and Genomics of Pediatric Neurological Disorders: An Overview of Current Insights and Future Directions

Pediatric neurological disorders comprise a highly heterogeneous group of conditions that together represent a substantial global public health burden. Many have a strong genetic basis and are associated with significant morbidity, premature mortality, and long-term disability, with far-reaching consequences for affected children, their families, and healthcare systems worldwide. Clinical heterogeneity is a hallmark of these disorders, as pathogenic variants in the same gene can give rise to diverse phenotypes with variable severity, age at onset, and disease course. In children, ongoing brain development and somatic growth further complicate diagnosis, often leading to nonspecific or atypical presentations that differ from classical adult neurological phenotypes. Advances in genetics and genomics have fundamentally transformed the understanding, diagnosis, and classification of pediatric neurological diseases. The widespread use of high-throughput sequencing, genome-wide association studies, and integrative bioinformatics approaches has enabled the rapid and precise identification of disease-associated genes, even in sporadic and complex conditions, facilitating earlier and more accurate diagnoses and highlighting the role of genetic background and gene–environment interactions in disease pathogenesis. Here we provide an overview of the genetic and genomic landscape of key pediatric neurological disorders with well-characterized molecular etiologies, including neuromuscular disorders, epilepsies, neurodevelopmental disorders, neurodegenerative diseases, and movement disorders. Current knowledge is synthesized with emphasis on clinical presentation, genetic architecture, and genotype–phenotype correlations. Gene-specific management strategies and emerging precision therapies are discussed for selected conditions, underscoring the central role of genetic diagnosis in guiding clinical decision-making and improving outcomes in affected children.