Jul 2026· Genetics and Molecular Research· 0 citations· 35 references
TL;DR
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.
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.
This review synthesizes contemporary insights into the genetic and molecular pathophysiology of seizures and epilepsy, with emphasis on mechanisms that destabilize excitation–inhibition balance, promote epileptogenesis, and drive pharmacoresistance and supports more refined approaches to epilepsy classification and future precision medicine strategies.
Mohammad Reza Seyedtaghia, Jina Babanzadeh, Marcello Scala et al.· Epilepsia Open· 0 citations
Four major themes are identified, encompassing genetic modifiers, epigenetic modifications, mosaicism, and environmental factors that may act independently or interactively to influence pathogenic burden and functional network balance, ultimately determining whether a pathogenic mutation manifests clinically.
Jiao-Jiao Xu, Dian-Fu Chen, Zhi-Ying Wu· Journal of genetics and geno...· 0 citations
BACKGROUND
Autism spectrum disorder (ASD) is a neurodevelopmental condition including incorrect functioning in communication, social interaction, and repetitive behavior. Global prevalence is estimated as 1-2%, with a predominance of men. Different pre- and perinatal, environmental, immunological, neurobiological, genetic, and epigenetic factors are involved in the etiology of ASD. The study aims to analyze genetic abnormalities in patients with ASD according to data from the current literature.
MATERIALS AND METHODS
Studies available in the PubMed and Google Scholar databases were chosen through a literature search. Only papers published from 2020, available as full-text publications in English, with studies conducted on humans, original papers, or meta-analyses were included.
RESULTS AND DISCUSSION
The following types of genetic variation were identified: copy number variants, larger insertions, inversions, uniparental disomies, tandem repeat expansions, common single nucleotide polymorphisms, single nucleotide variants, short insertions/deletions, and mitochondrial variants. Epigenetic factors, like histone modifications, deoxyribonucleic acid (DNA) methylation, and micro ribonucleic acid might play an important role in ASD predisposition. Genes identified in the review were mainly involved in neurodevelopment, synaptic formation, neuronal migration, neurotransmission, glial proliferation, ubiquitination, chromatin remodeling, or transcription. ASD is described as a component of the phenotype in fragile X syndrome, tuberous sclerosis complex, neurofibromatosis type 1, Angelman, Phelan-McDermid, Smith-Lemli-Opitz syndromes, and chromosome trisomies. Current guidelines for genetic diagnosis of ASD recommend performing directed genetic studies in the first line (like multiplex ligation-dependent probe amplification - MLPA, analysis of FMR1 gene), in case of a negative result, chromosomal microarray as a routine method, then next-generation sequencing (NGS) panel testing, WES (whole exome sequencing), or even WGS (whole genome sequencing) as the last test.
CONCLUSIONS
Wider access to modern diagnostic methods has increased the number of ASD patients in whom the genetic etiology of the disorder has been uncovered. Knowledge of the genetic background would be applicable in the diagnosis, prevention, prognosis, and individualized treatment.
G. Ręka, Katarzyna Wojciechowska, Monika Lejman· BMC Medical Genomics· 0 citations
Based on the experimental interventions identified in the 22q11DS studies, it is informed on the supportive therapies possible now and the future potential of curative interventions, and examples of how the multifaceted pathophysiological mechanisms and rescue strategies can have convergent effects at the molecular, synaptic, cellular and circuit levels.
P. Devaraju· Progress in neurobiology· 0 citations
CASK-related disorders may present with severe neurodevelopmental impairment and cerebral palsy–like phenotypes, even in the absence of characteristic neuroimaging findings, which should raise suspicion for CASK-related disorders.
I. Pacheva, Elena Timova, T. Todorov et al.· Frontiers in Psychiatry· 0 citations
An in-depth analysis of the genetic and molecular mechanisms of the FOXP2-CNTNAP2 pathway will not only contribute to understanding the pathogenesis of ASD and speech disorders but also offer potential molecular markers for diagnosing related conditions.
Fanglin Song, X. Li, Cheng Cheng et al.· Journal of neural transmissi...· 0 citations