Diagnostic Utility of Chromosomal Microarray Analysis in a Turkish Pediatric Cohort: Insights from 1,022 Patients with Neurodevelopmental Disorders and Congenital Anomalies.

BACKGROUND

Chromosomal microarray analysis (CMA) is a first-tier diagnostic test for children with unexplained developmental and/or congenital anomalies. This study aimed to evaluate the diagnostic contribution of CMA in a large, phenotypically diverse Turkish pediatric cohort.

METHODS

CMA was performed in 1,022 children presenting with developmental delay, intellectual disability, autism spectrum disorder, epilepsy, and/or congenital anomalies. Copy number variants (CNVs) were classified as pathogenic, likely pathogenic, or variants of uncertain significance based on American College of Medical Genetics guidelines.

RESULTS

CNVs were identified in 279 patients (27.3%), totaling 315 CNVs. Of these, 151 patients (14.8%) carried at least one pathogenic or likely pathogenic CNV, representing the diagnostic yield of the study. CNVs were more frequently classified as pathogenic when presenting as deletions. The diagnostic rate was higher among patients with syndromic features (20.2%) compared to those with isolated developmental delay/intellectual disability (11.8%). Among patients with CNVs, 139 (49.8%) exhibited phenotypes consistent with well-characterized genomic syndromes. In addition, rare but clinically significant CNVs were also identified, involving well-established dosage-sensitive genes. Notably, chromosomes X, 15, and 16 were among the most frequently affected, reflecting known genomic hotspots associated with neurodevelopmental and structural phenotypes.

CONCLUSION

CMA is a powerful diagnostic tool in the evaluation of pediatric patients with neurodevelopmental and structural disorders. This study emphasizes the added value of high-resolution CNV detection and careful clinical phenotyping to optimize diagnostic yield and guide precision care in clinically heterogeneous pediatric populations.