Uncovering the Genetic Landscape of Pediatric Neutropenia: Insights from a Case Series

Background Neutropenia in children presents with diverse etiologies, including genetic causes that remain incompletely understood. This study investigates the prevalence and clinical relevance of genetic variants in pediatric neutropenia. Methods Genetic testing was performed on 29 children diagnosed with neutropenia using commercial clinical sequencing panels. Variants were assessed for pathogenicity using ACMG guidelines and population frequency data. Results Genetic alterations were identified in 19 patients (66%), with most variants classified as variants of uncertain significance (VUS). Despite inconclusive pathogenicity, the majority of these variants had population frequencies below 0.1%, suggesting a plausible association with neutropenia. Recurrent mutations were observed in VPS13B, MECOM, LYST, RECQL4, and G6PD, with VPS13B being the most frequently affected gene. Conclusion The findings highlight the genetic heterogeneity of childhood neutropenia and the potential clinical utility of early genetic screening. Identification of high-risk mutations, such as those in MECOM, may inform treatment decisions and long-term management. Further research is needed to validate the pathogenicity of rare variants and improve diagnostic precision through expanded genomic databases and collaborative studies.