GENETIC AND MOLECULAR MECHANISMS IN PEDIATRIC NEUROLOGICAL DISORDERS: A SYSTEMATIC REVIEW

Abstract

Pediatric neurological disorders represent a heterogeneous group of conditions characterized by early-onset impairment in cognitive, motor, and behavioral functions, with significant lifelong consequences. This systematic review aims to synthesize current evidence on the genetic and molecular mechanisms underlying these disorders. A comprehensive literature search was conducted across major databases following PRISMA 2020 guidelines, resulting in the inclusion of 15 high-quality studies. The findings highlight a predominantly de novo–driven genetic architecture, with key contributions from rare variants and copy number variations affecting neurodevelopmental pathways. At the molecular level, consistent disruptions were identified in synaptic signaling, ion channel regulation, and excitatory–inhibitory balance, indicating strong pathway-level convergence despite gene-level heterogeneity. These mechanisms were found to underlie major disorder categories, including autism spectrum disorder, epileptic encephalopathies, and intellectual disability. The review further emphasizes the importance of genotype–phenotype relationships, although variability in clinical expression remains a challenge. Advances in next-generation sequencing have significantly improved early diagnosis and facilitated the transition toward precision medicine approaches. However, gaps remain in translating molecular findings into targeted therapies due to limited functional validation and clinical trials. The study provides an integrated framework linking genetic variation to molecular dysfunction and clinical outcomes, offering valuable insights for future research and therapeutic development in pediatric neurology.