Neurodevelopmental disorders (NDDs), such as autism spectrum disorder and intellectual disability, arise from complex interplays between genetic susceptibility and early environmental exposures. While significant advances have been made in identifying numerous genetic risk variants and the impact of discrete perinatal events like hypoxia-ischemia, research in these two domains often proceeds in parallel. A critical knowledge gap is understanding how specific genetic backgrounds modulate the brain's response to perinatal insults, and conversely, how such insults influence the penetrance and expressivity of genetic variants. This siloed approach limits our ability to predict individual outcomes or develop targeted interventions. The primary challenge lies in dissecting the mechanistic pathways underlying this gene-environment interplay. This Research Topic, therefore, aims to bridge this divide by curating studies that explicitly integrate genetic and perinatal perspectives, leveraging multi-omics, longitudinal cohort designs, and novel experimental models to build a unified understanding of NDD pathogenesis.

Goal

The primary goal of this Research Topic is to move beyond siloed approaches and foster a unified understanding of how genetic predispositions and perinatal insults interact to shape neurodevelopmental outcomes. We aim to curate a collection of high-quality original research and reviews that explicitly bridge these domains. Specifically, we seek to:

1. Elucidate the biological mechanisms (e.g., epigenetic, inflammatory, metabolic) through which specific genetic variants modulate vulnerability or resilience to perinatal adverse events.
2. Investigate how perinatal insults influence the clinical presentation, penetrance, and severity of known genetic disorders.
3. Identify novel convergent pathways and biomarkers that arise from the interplay of genetic and perinatal factors, which could inform early risk stratification.
4. Encourage translational studies that leverage this integrated knowledge to propose novel preventive or therapeutic strategies. By synthesizing evidence across disciplines, this collection will establish a more holistic framework for understanding NDD pathogenesis and pave the way for personalized early interventions.

Scope and Information for Authors

We welcome submissions of Original Research, Reviews, and Methodological articles that explicitly integrate genetic and perinatal factors. Specific themes include, but are not limited to:

• Multi-omics studies (genomic, epigenomic, transcriptomic) that identify molecular pathways linking perinatal insults to neurodevelopmental outcomes in genetically defined cohorts or model systems.

• Mechanistic investigations into gene-environment interactions, exploring how specific genetic mutations (e.g., in synaptic genes) alter neuronal resilience to perinatal hypoxia, inflammation, or nutrient deprivation.

• Clinical and translational research focusing on how perinatal events modulate the expressivity of genetic syndromes (e.g., 22q11.2 deletion, Fragile X) and vice versa.

• Advanced neuroimaging studies that correlate early brain structural/functional connectivity changes with genetic liability and perinatal complications.

• Epidemiological and large-scale cohort studies examining the interactive effects of polygenic risk scores and specific perinatal adversities on NDD risk. All manuscripts should directly address the interplay between genetic predispositions and perinatal events.

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Advances in Understanding Neurodevelopmental Disorders: Integrating Genetic Etiologies and Perinatal Insults