Chromosomal Aberrations in Pediatric Patients With Moderate/Severe Developmental Delay/Intellectual Disability With Abundant Phenotypic Heterogeneities: A Single-Center Study.

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.