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. 2025 Jun 23:16:1539902.
doi: 10.3389/fgene.2025.1539902. eCollection 2025.

Uncovering genetic contributors to developmental delay and intellectual disability: a focus on CNVs in pediatric patients

Yilun Tao #  1   2 , Hongzhi Guo #  3 , Dong Han #  1 , Miao Yang  3 , Ting Lun  3 , Lihong Wang  4 , Wenxia Song  1 , Haiwei Wang  5 , Xiaoze Li  1
Affiliations

Uncovering genetic contributors to developmental delay and intellectual disability: a focus on CNVs in pediatric patients

Yilun Tao et al. Front Genet. .

Abstract

Background: Developmental delay (DD) and intellectual disability (ID) are prevalent in children and often have genetic causes, particularly copy number variations (CNVs). Chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) are key diagnostic tools for identifying genetic contributions to these disorders. This study assesses the prevalence and clinical impact of CNVs in pediatric DD and ID patients.

Methods: Ninety-nine pediatric patients with DD or ID underwent CMA or WES. Of these, 82 received SNP array analysis, while 17 had WES. CNV pathogenicity was assessed using established databases and ACMG guidelines, with inheritance patterns determined where possible.

Results: Across the 99 patients, 43 CNVs were identified in 40 individuals, with 32 classified as clinically significant, resulting in a diagnostic rate of 30.3%. These findings included 24 deletions (75%), 7 duplications (22%), and 1 instance of loss of heterozygosity (3%). Of the CNVs with known inheritance, 65.2% were de novo. Recurrent CNVs made up 36.4% of the total, especially in regions 15q11.2-q13.1, 16p11.2, and 22q11.2. Additionally, 11 CNVs were categorized as variants of uncertain significance (VOUS).

Conclusion: This study supports CMA as an effective diagnostic tool for DD and ID, highlighting the importance of family-based CNV testing for genetic counseling. The findings emphasize the need for comprehensive genetic testing to improve diagnostic accuracy, with future multi-omics approaches potentially clarifying VOUS mechanisms and CNV variability in neurodevelopmental disorders.

Keywords: SNP array; WES; copy number variations; developmental delay; intellectual disability.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Distribution of CNV types. (a) The number and proportion of deletions, duplications, and loss of heterozygosity (LOH) among all detected CNVs (n = 43). (b) The number and proportion of deletions, duplications, and LOH among clinically significant CNVs (n = 32). (c) Inheritance pattern of all detected CNVs (n = 43).
FIGURE 2
FIGURE 2
Chromosomal distribution of pathogenic or likely pathogenic CNVs.
See this image and copyright information in PMC

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