• Role of Copy Number Variations in Neurodevelopmental Disorders
  • Ali Rezaei,1 Paria sadat Aghaseyedmirzaei,2 Shirin Farivar,3,*
    1. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University
    2. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University
    3. Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University


  • Introduction: Neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy, present diverse genetic patterns in their development. The pathogenesis of NDDs receives significant contribution from copy number variations (CNVs), which describe genomic segments that are either deleted or duplicated. The development of genomic technologies has enabled scientists to gain a better understanding of how CNVs affect gene expression through gene dosage changes and their combined effects with environmental factors. The focus of this research is on recent evidence of CNVs’ role in NDDs.
  • Methods: The research used a structured literature review method to analyze recent studies about CNVs and NDDs from 2020 to 2025. The research drew from scientific articles that studied autism spectrum disorder, epilepsy, intellectual disability, and their associated conditions. The selection criteria for studies included research that discovered new CNV connections and explained functional processes and clinical effects of these genetic variations. The analysis presents findings through thematic organization to demonstrate shared results between different research groups and study approaches.
  • Results: 1. Prevalence and Genetic Contribution Large-scale genomic research has proven that CNVs exist as a major cause of NDD cases. The occurrence of pathogenic CNVs reaches 10-20% in people with ASD, epilepsy, and ID, but these numbers increase in severe or syndromic cases. 2. Hotspot Regions and Recurrent CNVs The genomic regions such as 16p11.2, 22q11.2, and 1q21.1 have proven to be recurrent hotspots that link to different NDDs. Research indicates that certain CNV locations with variable expression can lead to varying levels of cognitive impairment ranging from mild to severe intellectual disability. 3. Functional Mechanisms Research demonstrates that CNV disruptions can cause neurodevelopmental disorders by affecting gene dosage, synaptic dysfunction, and neuronal signaling. Research indicates that CNVs that affect synaptic genes and chromatin regulators can lead to ASD and epilepsy development. 4. Clinical Applications and Diagnostics The combination of whole-genome sequencing (WGS) with CNV analysis has resulted in better diagnostic outcomes for NDDs. Medical organizations have established CNV testing as the primary diagnostic method for patients who show unexplained ID or ASD. WGS-based CNV detection have discovered new pathogenic variants which standard microarray tests failed to detect. 5. Emerging Insights: Polygenic and Environmental Interactions Research indicates that CNVs function together with rare genetic variants and multiple genetic risk factors. The penetrance of CNV depends on environmental factors which demonstrate the need to study gene-environment interactions.
  • Conclusion: Research indicates that CNVs function as an important genetic factor that causes neurodevelopmental disorders and diverse phenotypic outcomes. The development of genomic technologies has improved our ability to detect and understand CNVs, which leads to better diagnostic methods and risk assessment. Future research should explore the interaction of CNVs with polygenic risk and environmental exposures. However, current research has several limitations and criticisms: • Incomplete penetrance and variable expressivity: Because many CNVs do not lead to disease, and their effects vary greatly across individuals, clinical interpretation is still challenging. • Limited functional understanding: Although associations are identified, the exact molecular mechanisms by which CNVs cause NDDs remain unclear. • Diagnostic disparities: Access to advanced genomic testing like WGS is limited in many regions, which leads to underdiagnosis and unequal healthcare outcomes. • Small sample sizes and cohort diversity: The generalizability of the findings is limited because many CNV studies rely on limited or homogeneous populations. • Overemphasis on genetics: CNVs are often studied in isolation, with insufficient integration of environmental factors and polygenic influences, which is in contrast with the complex NDD etiology.
  • Keywords: Copy number variations; Neurodevelopmental disorders; Autism; Intellectual disability; Epilepsy