Leukoencephalopathy with Vanishing White Matter (VWM) Presenting with Early Myoclonic Encephalopathy (EME) and Rapid Progressive Internal Hydrocephalus

Background/Purpose: Leukoencephalopathy with VWM is a neurodegenerative disorder mostly beginning during the first years of life with abnormalities of muscle tone and ataxia. Febrile episodes, vaccinations or mild trauma can result in acute deteriorations. Usually early onset is associated with rapid progression. Epileptic seizures can appear during the course, whereas hydrocephalus has not been reported yet as clinical symptom. Causative autosomal recessive mutations in the genes ElF2B 1–5 result in increased susceptibility for intracellular stress. Another diagnostic feature is a characteristic disease pattern on cerebral MRI.

Methods: Case report.

Results: We report a Jesidic girl with therapy-resistant myoclonic epilepsy 4 weeks after normal birth, pregnancy, and perinatal period. Several weeks later, she developed significant muscular hypotonia. Extensive metabolic workup gave no valuable abnormalities. Her cMRI at 6 weeks showed delayed myelination with no progress 2 months later. Due to this observation, molecular analysis of ElF2B genes was performed and a new homozygous mutation in ElF2B5 (c 722G > A) was detected. Both parents (higher degree cousins) were heterozygous carriers. At 7 months of age, the girl developed rapid progressive internal hydrocephalus with vomiting and abnormal head growth. She died 10 days later under palliative care.

Conclusion: Leukoencephalopathy with VWM is a rare reason for early onset catastrophic infantile epilepsy. The clinical course of the disease is highly variable; in this case, rapidly progressive internal hydrocephalus accompanied acute deterioration of the patient’s state. So far, hydrocephalus was not observed as a clinical sign of VWM.