Clinical and genetic characteristics of pediatric patients with vanishing white matter disease: a retrospective single-center study

Abstract

ObjectiveVanishing 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 methodsMedical records of four patients followed up at the Department of Pediatrics, Faculty of Medicine, Firat University, Elaz & imath;& gbreve;, T & uuml;rkiye were retrospectively reviewed. Demographic data, clinical presentation, magnetic resonance imaging (MRI) findings, and genetic analysis results were evaluated for all patients. Genetic testing was performed using whole-exome sequencing (WES).ResultsThree patients were male and one female. Parental consanguinity was present in all families (second-degree cousins). The mean age at diagnosis was 2.0 +/- 1.35 years. The most common presentations were vomiting and infection-related neurological deterioration. Epilepsy was present in three patients. Brain MRI showed diffuse hypomyelination, frontoparietal periventricular white matter involvement, and cystic degeneration. Pathogenic variants were identified in the EIF2B5 and EIF2B4 genes in three and one patient, respectively. Variable ages of onset and disease courses were observed in patients carrying different EIF2B variants. Two patients died early, and two remained bedridden.ConclusionVWM is a rare childhood leukoencephalopathy characterized by stress-triggered neurological deterioration and clinical variability. Accurate diagnosis requires the combined evaluation of clinical findings, MRI features, and genetic results. VWM should be considered in children with consanguinity and neurological deterioration following an infection.