Expanded Phenotypes of Vanishing White Matter disease (P3.328)

Objective: To discuss expanded phenotypes of Vanishing White Matter disease (VWM). Background: VWM is characterized by progressive cerebellar ataxia, spasticity, variable optic atrophy and relatively preserved mental abilities. Chronic progression occurs, with episodes of rapid deterioration following febrile infections or minor head trauma. Diagnosis requires typical clinical features, characteristic MRI abnormalities, identifiable pathogenic variants in one of five genes (EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5). Design/Methods: Case report of 4 children seen at a tertiary pediatric hospital, diagnosed with VWM. Results: Patient 1: 8 year old male, who developed spasticity at 2 years of age. MRI showed classic findings of leukodystrophy. Whole Exome Sequencing (WES) showed mutation in EIF2B5. Regression occurred with minor head trauma. He is currently wheelchair-bound, has intact receptive language and uses eye recognition software for communication. Patient 2: 3 year old female with recurrent status epilepticus at 5 months of age. MRI done at 6 months did not show leukodystrophy. Repeat MRI at 19 months showed characteristic findings. WES showed mutation in EIB2B5. Regression occurred at 22 months, following teething. Patient 3: 15 month old male, with developmental delay and spasticity at 7 months. MRI showed leukodystrophy, with dysmorphic ventricular system. VUS showed mutation in EIF2B2. Neurologic status remained stable without significant regression since diagnosis. Patient 4: 10 year old male diagnosed incidentally from MRI done for ‘dizziness’, showing leukodystrophy. WES showed mutation in EIF2B3. He did not have ataxia, spasticity nor regression. Conclusions: Patient 1 has classically described phenotype of VWM. Patient 2 has infantile form of the disease but without rapid progression during infancy. Patient 3 has unique MRI findings and has not had progression. Patient 4 was diagnosed pre-symptomatically. VWM requires the described genetic mutation, but selective vulnerability and timing factor may be involved. Using WES, patients may be diagnosed pre-symptomatically. Disclosure: Dr. Amin has nothing to disclose. Dr. Desai has nothing to disclose. Dr. Emrick has nothing to disclose.