Focal status and acute encephalopathy in a 13-year-old boy with de novo DNM1L mutation: Video-polygraphic pattern and clues for differential diagnosis

Background: Pathogenic variants in the dynamin 1 like gene are related to abnormal mitochondrial dynamics and distributions and are associated to variable clinical phenotypes. A few patients harboring the p.Arg403Cys missense variant appears to be different from the classical, more severe phenotypes, showing sudden onset of drug resistant seizures after a previously normal or slightly delayed development. Case report: We report on a boy with abrupt onset of focal status and coma at the age of 13, initially treated as autoimmune encephalitis, with final diagnosis of de novo missense p.Arg403Cys variant in the DNM1L gene. Discussion: We compare his clinical, electrophysiological, biochemical, neuroradiological and histopathological picture to the rare cases reported to date and provide diagnostic clues that can help clinicians in differentiate p.Arg403Cys-related phenotype from that of immune-mediated encephalopathies. Conclusion: The clinical picture related to p.Arg403Cys mutations should be considered alongside acquired pathologies in the differential diagnosis of young patients with focal refractory epilepsy and encephalopathy, also occurring during late childhood or adolescence. Prompt genetic testing allows to avoid unnecessary treatments and procedures and to better define the prognosis and management strategies. (C) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Automated summary

Pathogenic variants in the DNM1L gene can result in abnormal mitochondrial dynamics and clinical phenotypes, with p.Arg403Cys mutation showing distinct features from immune-mediated encephalopathies. Prompt genetic testing is crucial for differential diagnosis and management of young patients with focal refractory epilepsy.