Exploring Copy Number Variants in a Cohort of Children Affected by ADHD: Clinical Investigation and Translational Insights.

Background/

Objectives

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder frequently associated with other neuropsychiatric conditions, characterized by high clinical heterogeneity and a complex genetic background. Recent studies suggest that copy number variations (CNVs) may contribute to ADHD susceptibility, particularly when involving genes related to brain development, attention regulation, and impulse control. This study investigated the association between CNVs and ADHD phenotype by identifying patients with and without potential pathogenic CNVs.

Methods

We evaluated 152 well-characterized ADHD pediatric patients through comprehensive clinical assessments, including dysmorphic features, brain MRI, EEG patterns, and cognitive testing. CNVs were identified using array Comparative Genomic Hybridization (array-CGH). Participants were classified as carrying potentially causative CNVs (PC-CNVs), non-causative CNVs (NC-CNVs), or without CNVs (W-CNVs) and statistically compared across clinical and neurodevelopmental measures.

Results

CNVs were identified in 81 participants (53%), comprising 13 with PC-CNVs (8.5%) and 68 with NC-CNVs (44.7%). ADHD symptoms were pronounced across all groups, but PC-CNVs showed a higher burden of comorbidities, suggesting a stronger genetic contribution to ADHD complexity. Significant differences were observed in oppositional behavior, inattentive symptoms, brain MRI findings, and developmental language anomalies. Several CNVs involved genes previously implicated in neurodevelopmental disorders, supporting a potential genetic contribution to the clinical complexity of ADHD.

Conclusions

This exploratory study supports the role of CNVs in ADHD susceptibility and highlights the value of genetic screening for understanding clinical variability. Larger studies are needed to clarify genotype-phenotype correlations in ADHD and to guide personalized clinical management.