Abstract

Background: This study aimed to examine the clinical usefulness of chromosome microarray (CMA) for selective implementation in patients with unexplained moderate or severe developmental delay/intellectual disability (DD/ID) and/or combined with different dysphonic features in the Han Chinese population. Methods: We retrospectively analyzed data on 122 pediatric patients with unexplained isolated moderate/severe DD/ID with or without autism spectrum disorders, epilepsy, dystonia, and congenital abnormalities from a single-center neurorehabilitation clinic in southern China. Results: A total of 46 probands (37.7%) had abnormal CMA results among the 122 study patients. With the exclusion of aneuploidies, uniparental disomies, and multiple homozygotes, 37 patients harbored 39 pathogenic copy number variations (pCNVs) (median [interquartile range] size: 3.57 [1.6 to 7.1] Mb; 33 deletions and 6 duplications), enriched in chromosomes 5, 7, 15, 17, and 22, with a markedly high prevalence of Angelman/Prader-Willi syndrome (24.3% [nine of 37]). Three rare deletions in the regions 5q33.2q34, 17p13.2, and 13q33.2 were reported, with specific delineation of clinical phenotypes. The frequencies of pCNVs were 18%, 33.3%, 38.89%, 41.67%, and 100% for patients with 1, 2, 3, 4, and 5 study phenotypes, respectively; patients with more concomitant abnormalities in the heart, brain, craniofacial region, and/or other organs had a higher CMA diagnostic yield and pCNV prevalence (P < 0.05). Conclusions: Clinical application of CMA as a first-tier test among patients with moderate/severe DD/ID combined with congenital structural anomalies improved diagnostic yields and the quality of clinical management in this series of patients.

Keywords

Autism spectrum disorders, Chromosome microarray analysis, Congenital heart disease, Developmental delay/intellectual disability, Multiple congenital anomalies

Document Type

Journal Article

Date of Publication

10-1-2023

Volume

147

Publication Title

Pediatric Neurology

Publisher

Elsevier

School

School of Medical and Health Sciences / Centre for Precision Health

RAS ID

61870

Funders

Special Funds for Science and Technology in Guangdong Province / Shantou Medical and Health Science and Technology Plan Project / National Natural Science Foundation of China / Shenzhen Key Projects of Basic Research

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Comments

Wu, D., Wu, Y., Lan, Y., Lan, S., Zhong, Z., Li, D., . . . Ma, L. (2023). Chromosomal aberrations in pediatric patients with moderate/severe developmental delay/intellectual disability with abundant phenotypic heterogeneities: A single-center study. Pediatric Neurology, 147, 72-81. https://doi.org/10.1016/j.pediatrneurol.2023.06.001

First Page

72

Last Page

81

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Link to publisher version (DOI)

10.1016/j.pediatrneurol.2023.06.001