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© 2018 American Academy of Neurology. Catastrophic epileptic encephalopathy of unclear etiology following a mild metabolic insult generally has a poor outcome. Here, we present 2 such unrelated individuals in whom whole-exome sequencing identified the same de novo recurrent mutation (c.1207C>T p.Arg403Cys) in the gene encoding the guanosine triphosphatase (GTPase) Dynamin-1 like Protein (DNM1L) (reference sequence NM-012062.4). The dynamic fission and fusion of the intracellular mitochondrial network are essential to facilitate mitophagy and thusmitochondrial quality and function. 1 Duringmitochondrial division, the GTPase DNM1L forms multimeric collars at specific fission sites, constricting portions of the mitochondrial reticulum and generating fragments for engulfment and degradation. 2 DNM1L has been implicated in several presentations of refractory epilepsy. 3 Both of our patients exhibited signs of preexisting developmental delay and presented with epilepsy during, or recently following, a febrile illness or exercise. Elevated lactate levels, epilepsia partialis continua, nonspecific imaging, and evidence of lipid storage myopathy all support mitochondrial dysfunction (See table for presentation summary and e-case report for details, links.lww. com/NXG/A63). This evidence supports an etiological role for DNM1L in mitochondrial epilepsy syndrome with fever sensitivity (MEFS).

Original publication




Journal article


Neurology: Genetics

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