Genetic Insights into the Comorbidity of Congenital Heart Disease and Neurodevelopmental Disorders: Focus on Copy Number Variations.
- 1Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
- 2Department of Neurology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
- 3NHC Key Laboratory of Birth Defects Prevention, Institute of Reproductive Health, Henan Academy of Innovations in Medical Science, Zhengzhou 451163, China.
Abstract
Congenital heart disease (CHD) and neurodevelopmental disorders (NDDs) frequently co-occur, indicating that cardiac and neural phenotypes can arise from shared developmental disturbances rather than exclusively from the physiological consequences of heart disease. Copy number variations (CNVs) provide a major genomic basis for this overlap, but their effects extend beyond changes in protein-coding gene dosage. This review synthesizes evidence from recurrent CNV syndromes, genomic cohorts, developmental studies, and experimental models to define how CNVs jointly influence heart and brain development. We examine four interconnected mechanisms: dosage alteration of pleiotropic and multiple genes, disruption of non-coding regulatory elements, remodeling of non-coding RNA networks, and reorganization of three-dimensional chromatin architecture. We further describe how developmental timing, cell-type-specific regulatory context, additional genomic variants, cardiac physiology, and clinical exposures shape incomplete penetrance and variable expressivity. Together, these findings support a layered model in which a primary CNV establishes cross-organ susceptibility, whereas genetic and developmental modifiers determine whether CHD, NDD, or both become clinically manifest. Clinically, CNV diagnosis can inform neurodevelopmental surveillance, multisystem management, and genetic counseling. Genotype-first longitudinal cohorts, developmental multi-omics, parallel cardiac and neural models, and prospective clinical studies will advance individualized risk prediction and intervention.
Related
- SET Domain Genes in Neurodevelopmental Disorders
- Neurodevelopmental disorders in infants treated with anti-VEGF agents vs. laser photocoagulation or cryotherapy for ROP
- Parsing altered brain connectivity in neurodevelopmental disorders by integrating graph-based normative modeling and deep generative networks
- Copy number variants (CNVs) interfere with human accelerated regions (HARs) in neurodevelopmental disorders: a large-scale cohort study
- Vision In SyndrOmic Neurodevelopmental disorders-15q (VISiON-15q) study: eye tracking to supplement clinical examination for detection of cerebral/cortical visual impairment in children with Angelman and Duplication of 15q Syndromes
BibTeX
@article{ye2026genetic,
title = {{Genetic Insights into the Comorbidity of Congenital Heart Disease and Neurodevelopmental Disorders: Focus on Copy Number Variations.}},
author = {Ziyi Ye and Yingzhong He and Jing Guo and Jiajia Meng and Yufei Xu and Yingyan Wang and Bo Wang},
journal = {Journal of cardiovascular development and disease},
year = {2026},
month = oct,
doi = {10.3390/jcdd13100529},
url = {https://europepmc.org/article/MED/42930925},
note = {CC BY},
}
RIS
TY - JOUR
TI - Genetic Insights into the Comorbidity of Congenital Heart Disease and Neurodevelopmental Disorders: Focus on Copy Number Variations.
AU - Ziyi Ye
AU - Yingzhong He
AU - Jing Guo
AU - Jiajia Meng
AU - Yufei Xu
AU - Yingyan Wang
AU - Bo Wang
PY - 2026
DA - 2026/10/21
JO - Journal of cardiovascular development and disease
DO - 10.3390/jcdd13100529
UR - https://europepmc.org/article/MED/42930925
AB - Congenital heart disease (CHD) and neurodevelopmental disorders (NDDs) frequently co-occur, indicating that cardiac and neural phenotypes can arise from shared developmental disturbances rather than exclusively from the physiological consequences of heart disease. Copy number variations (CNVs) provide a major genomic basis for this overlap, but their effects extend beyond changes in protein-coding gene dosage. This review synthesizes evidence from recurrent CNV syndromes, genomic cohorts, developmental studies, and experimental models to define how CNVs jointly influence heart and brain development. We examine four interconnected mechanisms: dosage alteration of pleiotropic and multiple genes, disruption of non-coding regulatory elements, remodeling of non-coding RNA networks, and reorganization of three-dimensional chromatin architecture. We further describe how developmental timing, cell-type-specific regulatory context, additional genomic variants, cardiac physiology, and clinical exposures shape incomplete penetrance and variable expressivity. Together, these findings support a layered model in which a primary CNV establishes cross-organ susceptibility, whereas genetic and developmental modifiers determine whether CHD, NDD, or both become clinically manifest. Clinically, CNV diagnosis can inform neurodevelopmental surveillance, multisystem management, and genetic counseling. Genotype-first longitudinal cohorts, developmental multi-omics, parallel cardiac and neural models, and prospective clinical studies will advance individualized risk prediction and intervention.
SN - 2308-3425
ER -