| Popis: |
Purpose: The progressive myoclonus epilepsies (PMEs) are a group of symptomatic generalised epilepsies with a progressive course and poor outcome. Advances in molecular genetics have begun to elucidate the causes of PME, including Lafora disease, Unverricht Lundborg disease, neuronal ceroid lipofuscinosis, dentatorubral-pallidoluysian atrophy (DRPLA) and myoclonic epilepsy with ragged red fibres (MERRF). We report eIF2B related leucoencephalopathy with VWM as another cause of PME. Method: Detailed medical and family histories were obtained on the proband and his relatives. EEG, MRI and MRS of the brain, EMG, MRS of the muscle, skin-muscle-nerve biopsy, brain biopsy, bone marrow biopsy, CSF studies, metabolic work-up and molecular genetic studies for MERFF, DRPLA, spinocerebellar ataxia types 1 and 3, and VWM leucodystrophy were performed on the proband. Results: The proband, a 38 year-old man, developed learning problems at age 9, after head trauma with loss of consciousness. At age 22, he began to have myoclonic jerks as well as generalised tonic-clonic seizures. At age 38, he had a cerebellar syndrome with severe dysarthria and ataxia, as well as a bilateral pyramidal syndrome. Hewas wheelchair bound since age 31. The myoclonus that had been very disabling had almost disappeared. Infrequent brief generalised seizures persisted. EEGs showed diffuse slow waves and epileptic activity from both temporal regions. MRI showed marked selective loss of white matter volume with extreme thinning of the corpus callosum. Brain biopsy revealed loss of white matter. The proband was homozygous for the R113H mutation in the eIF2B5 gene. Conclusion: Mutations in any of the 5 genes encoding subunits of the translation initiation factor eIF2B can cause vanishing white matter leucodystrophy (VWM)/childhood ataxia with central nervous system hypomyelination (CACH). Mutations in these genes should be included in the differential diagnosis of progressive myoclonus epilepsy. |
