Global developmental delay: comparison of developmental profiles between gene-positive/suspicious positive and gene-negative cases.

backgroundGlobal developmental delay (GDD) is associated with genetic abnormalities; however, the specific clinical and developmental features that should trigger genetic testing remain unclear. In this study, we explored this issue.

methodsA total of 126 children with GDD were recruited for this study. Comprehensive medical histories and physical examination data were collected for all participants. The Chinese adaptation of the Griffiths Mental Development Scales was used to assess neurodevelopmental outcomes. Genetic variations were analyzed through trio-based whole exome sequencing and proband whole genome sequencing. A comparative analysis of the clinical characteristics was conducted between children with gene-positive/suspicious positive results (i.e., the mutation is deleterious or potentially deleterious, and the inheritance pattern and phenotype are matched) and those with negative results.

resultThe positive/suspicious positive rate of genes was 46.8%. The locomotor, performance, and general quotients were lower in the gene-positive/suspicious positive group than the gene-negative group (p < 0.05), and the lower the locomotor ability, the higher the gene positive/suspicious positive rate (p < 0.05).

conclusionChildren with GDD and genetic abnormalities exhibited poorer locomotor, performance, and general developmental quotients compared to those without genetic mutations. Furthermore, individuals with poorer locomotor ability should be prioritized for genetic testing. IMPACT: This study aimed to compare the clinical and developmental profiles of children with GDD who test positive or suspiciously positive for genetic abnormalities with those who test negative, and to identify key clinical features that may serve as indicators for genetic testing. It highlights that children with GDD and genetic abnormalities exhibited poorer locomotor, performance, and general developmental quotients compared to those without genetic mutations. Individuals with poorer locomotor ability should be prioritized for genetic testing. The findings supplement existing literature by providing insights to guide clinicians on determining which children with GDD should be considered for genetic testing.