Genetic investigations and implications of genetic diagnosis in childhood onset neurological and neurodevelopmental disorders

Neurological and neurodevelopmental disorders in childhood represent an area of growing interest in biomedical research, as they are among the leading causes of intellectual disability, motor impairment, and social-communicative difficulties in children. These conditions encompass a wide range of pathologies, including autism spectrum disorders (ASD), childhood epilepsies, cerebral palsy, global developmental delay, movement disorders, and numerous rare genetic diseases. Their clinical heterogeneity reflects an underlying biological complexity in which genetic factors play a key role. Over the past two decades, the advent of Next-Generation Sequencing (NGS) technologies has revolutionized the ability to identify genetic variants associated with these disorders, opening new diagnostic and therapeutic perspectives. Large-scale genomic studies have revealed numerous mutations, deletions, duplications, and chromosomal rearrangements that disrupt the development and function of the central nervous system from the earliest stages of life. Understanding the genetic basis of these disorders is essential for improving diagnostic accuracy, guiding early intervention strategies, and, in some cases, accessing targeted therapies. Moreover, integrating genetic, phenotypic, and neurobiological data allows for the development of new pathogenic models, contributing to a redefinition of traditional clinical classifications. This thesis aims to explore the role of genetics in neurological and neurodevelopmental disorders in childhood, analyzing the molecular mechanisms underlying major conditions, the currently available diagnostic techniques, and the clinical and bioethical implications of genomic medicine in the pediatric setting.