Clinical use of whole-genome sequencing in children with developmental delay or intellectual disability

Determining the underlying cause of developmental delay or intellectual disability (DD/ID) is challenging yet crucial. Establishing a genetic basis for cases of unexplained DD/ID is integral to informing clinical decisions and anticipating patient outcomes. In this report, we share our institutional insights derived from employing whole-genome sequencing (WGS) to investigate unexplained DD/ID in pediatric populations.

A retrospective study was conducted on 115 children aged 1 month to 16 years with unexplained DD/ID who underwent WGS. We analyzed demographic profiles and catalogued genetic variants identified, in conjunction with examining clinical variables potentially associated with diagnostic yield.

WGS data from 115 pediatric patients identified a total of 33 pathogenic or likely pathogenic single nucleotide variants and small insertions/deletions, of which 22 were classified as diagnostic cases and 11 as carriers. In addition, 11 pathogenic or likely pathogenic copy number variations were detected. Clinical attributes such as gender, age at diagnosis, gestational maturity, birth weight, perinatal complications (anoxia, jaundice), comorbid symptoms, hereditary background, neuromuscular function (muscle tone and strength), presence of epilepsy, neuroimaging, and electroencephalography patterns did not show a significant association with WGS findings. Nonetheless, a noteworthy association emerged between earlier age at diagnosis and increased diagnostic yield via WGS.

WGS serves as a powerful tool for uncovering genetic etiologies in children with unexplained DD/ID, with meaningful implications for clinical care, genetic counseling for families, and long-term management planning.