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Chromosomal Microarray in Children With Developmental Delay: The Experience of a Tertiary Center in Korea
Eun Hye Yang1, Yong Beom Shin2, Soo Han Choi1
1Department of Pediatrics, Pusan National University Hospital, Biomedical Research Institute, School of Medicine, Pusan National University, Busan, South Korea.
Insights
Chromosomal microarray (CMA) is a valuable genetic test for children with developmental delay (DD) and intellectual disability (ID). This study in Korean children found CMA useful, with pathogenic copy number variants (CNVs) linked to gene number and deletion type.
Area of Science:
- Genetics
- Pediatrics
- Medical Diagnostics
Background:
- Chromosomal microarray (CMA) is a primary genetic diagnostic tool for developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), and multiple congenital anomalies (MCA).
- Unexplained DD/ID in children necessitates advanced genetic testing to identify underlying causes.
Purpose of the Study:
- To evaluate the diagnostic utility and yield of CMA in a cohort of Korean children with unexplained developmental delay/intellectual disability.
- To analyze the characteristics of pathogenic copy number variants (CNVs) and their correlation with clinical phenotypes.
Main Methods:
- CMA was performed on 308 Korean children diagnosed with DD/ID between January 2010 and September 2020.
- The Affymetrix CytoScan 750 K array, offering an average resolution of 100 kb, was utilized for genetic analysis.
- Medical records were retrospectively reviewed to correlate genetic findings with clinical features.
Main Results:
- The overall diagnostic yield of CMA was 18.5%, identifying 70 pathogenic CNVs (PCNVs) in 57 patients.
- Deletion CNVs were significantly more frequent among PCNVs compared to non-PCNVs (P < 0.001).
- The number of genes within CNV intervals was significantly higher in PCNVs (average 8.6) than non-PCNVs (average 47.5) (P < 0.001), and short stature/hearing difficulties were more prevalent in the PCNV group.
Conclusions:
- CMA is an effective genetic testing method for Korean children with DD/ID, contributing to diagnosis and genetic counseling.
- The pathogenicity of CNVs is associated with the number of genes encompassed within the variant and the type of CNV (deletion), rather than the physical size of the CNV.
Abstract:
Background and Objectives: Chromosomal microarray (CMA) is a first-tier genetic test for children with developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), and multiple congenital anomalies (MCA). In this study, we report our experiences with the use of CMA in Korean children with unexplained DD/ID. Methods: We performed CMA in a cohort of 308 children with DD/ID between January 2010 and September 2020. We also retrospectively reviewed their medical records. The Affymetrix CytoScan 750 K array with an average resolution of 100 kb was used to perform CMA. Results: Comorbid neurodevelopmental disorders were ASD (37 patients; 12.0%), epilepsy (34 patients; 11.0%), and attention deficit hyperactivity disorders (12 patients; 3.9%). The diagnostic yield was 18.5%. Among the 221 copy number variants (CNVs) identified, 70 CNVs (57 patients; 18.5%) were pathogenic. Deletion CNVs were more common among pathogenic CNVs (PCNVs) than in non-PCNVs (P < 0.001). The size difference between PCNVs and non-PCNVs was not significant (P = 0.023). The number of included genes within CNV intervals was significantly higher in PCNVs (average 8.6; 0-347) than in non-PCNVs (average 47.5; 1-386) (P < 0.001). Short stature and hearing difficulty were also more common in the PCNV group than in the non-PCNV group (P = 0.010 and 0.070, respectively). Conclusion: This study provides additional evidence for the usefulness of CMA in genetic testing of children with DD/ID in Korea. The pathogenicity of CNVs correlated with the number of included genes within the CNV interval and deletion type of the CNVs, but not with CNV size.