A Rare Cause of Progressive Spastic Motor Impairment in a Child: Vanishing White Matter Disease Due to Novel EIF2B1 Compound Heterozygosity—A Case Report with Physiotherapy Correlation

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Background: Leukoencephalopathy with vanishing white matter (VWM), also known as childhood ataxia with central nervous system hypomyelination, is a rare autosomal recessive leukodystrophy caused by pathogenic variants in EIF2B1–EIF2B5; EIF2B1-related disease is comparatively uncommon. Case Presentation: An 11-year-old girl with essentially normal early development developed progressive loss of motor milestones and spasticity from approximately four years of age. Brain magnetic resonance imaging demonstrated near-symmetrical T2-weighted and FLAIR hyperintensity of the bilateral cerebral white matter with periventricular cystic change, additional involvement of deep grey matter, brainstem and cerebellar grey matter, and diffuse thinning of the corpus callosum. Whole mitochondrial genome sequencing was unremarkable. Clinical exome sequencing identified likely compound heterozygous EIF2B1 variants, c.439C>T (p.Arg147Ter) and c.824A>G (p.Tyr275Cys), supporting a diagnosis of EIF2B1-related VWM. At neuropaediatric physiotherapy assessment, lower-limb-predominant spasticity was evident, with Modified Ashworth Scale grades up to 3 at the knee flexors and ankle plantar flexors, brisk deep tendon reflexes, bilateral extensor plantar responses, bilateral knee flexion contracture, and marked limitation of standing and walking. Gross Motor Function Measure dimension scores were 100% for lying/rolling, 100% for sitting, 63.85% for crawling/kneeling, 19.14% for standing, and 0% for walking/running/jumping. Speech, cognition, and attention remained age-appropriate. Conclusion: The case demonstrates the complementary diagnostic roles of neuroimaging and molecular testing and the value of structured physiotherapy outcome measures for rehabilitation planning in progressive VWM.