Genetic analysis of 280 children with unexplained developmental delay or intellectual disability using whole exome sequencing.

INTRODUCTION

Developmental delay (DD) and intellectual disability (ID) are key manifestations of neurodevelopmental disorders (NDDs), characterized by considerable clinical and genetic variability, which complicates genetic diagnosis. Whole exome sequencing (WES) has become an effective method for uncovering genetic causes in patients with unexplained DD/ID.

METHODS

We retrospectively analyzed WES data from 280 patients diagnosed with unexplained DD/ID. Demographic information and genetic variants identified through WES were assessed, along with an evaluation of clinical factors that might influence the detection of genetic causes.

RESULTS

Pathogenic variants were detected in 73 cases (36.07%), including 25 cases involving pathogenic chromosomal copy number variations. Clinical factors such as age, sex, gestational age, birth weight, anoxia, jaundice, associated symptoms, family history, muscle strength, muscle tone, epilepsy, brain MRI findings, EEG results, and the severity of DD/ID did not significantly impact the WES outcomes. However, a significant correlation was observed between delivery mode and positive WES results, with a higher diagnostic yield among patients delivered via caesarean section.

CONCLUSIONS

WES is a valuable approach for identifying genetic causes in patients with unexplained DD/ID, providing benefits for patient management, family genetic counseling, and long-term prognosis assessment.

CLINICAL TRIAL NUMBER

Not applicable.