Clinical and Genetic Characteristics of Pediatric Patients with Vanishing White Matter Disease: A Retrospective Single-Center Study

Objective Vanishing White Matter Disease (VWM) is a rare autosomal recessive leukoencephalopathy caused by pathogenic variants in the EIF2B gene complex. This study aimed to describe the clinical, radiological, and genetic characteristics of four genetically confirmed pediatric patients with VWM who were followed up at our center. Materials and Methods Medical records of four patients followed up at the Department of Pediatrics, XXX School of Medicine, were retrospectively reviewed. Demographic data, clinical presentation, magnetic resonance imaging (MRI) findings, and genetic analysis results were also evaluated. Genetic testing was performed using whole-exome sequencing. (WES). Results Three patients were male, and one was female; second-degree consanguinity was present in all families. The mean age at diagnosis was 2.0 ± 1.35. The most common presenting features were vomiting and infection-related neurological deterioration. Epilepsy was identified in three patients. Brain MRI revealed diffuse hypomyelination, frontoparietal periventricular white matter involvement, and cystic degeneration in all cases. Pathogenic variants were identified in the EIF2B5 and EIF2B4 genes in three and one patient, respectively. Two patients died at an early age, and two remained bedridden. Conclusion VWM is a rare childhood leukoencephalopathy characterized by stress-induced neurological deterioration and marked clinical heterogeneity. Early and accurate diagnosis requires integration of clinical findings with characteristic MRI features and genetic analysis; VWM should be considered in children with consanguinity and unexplained neurological decline following infection.