Conor S Ryan1, Anthony L Fine1, Alexander L Cohen1, Brenda M Schiltz2, Deborah L Renaud1, Elaine C Wirrell1, Marc C Patterson1,3, Nicole J Boczek4,5, Raymond Liu6, Dusica Babovic-Vuksanovic3, David C Chan6, Eric T Payne1. 1. 1 Department of Neurology, Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, MN, USA. 2. 2 Department of Pediatrics, Division of Critical Care Medicine, Mayo Clinic, Rochester, MN, USA. 3. 3 Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA. 4. 4 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 5. 5 Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA. 6. 6 Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Abstract
BACKGROUND: The dynamin 1-like gene ( DNM1L) encodes a GTPase that mediates mitochondrial and peroxisomal fission and fusion. We report a new clinical presentation associated with a DNM1L pathogenic variant and review the literature. RESULTS: A 13-year-old boy with mild developmental delays and paroxysmal dystonia presented acutely with multifocal myoclonic super-refractory status epilepticus. Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy. Rapid trio-whole exome sequencing revealed a de novo heterozygous c.1207C>T (p.R403C) pathogenic variant in DNM1L. Immunofluorescence staining of fibroblast mitochondria revealed abnormally elongated and tubular morphology. CONCLUSIONS: This case highlights the diagnostic importance of rapid whole exome sequencing within a critical care setting and reveals the expanding phenotypic spectrum associated with DNM1L variants. This now includes progressive paroxysmal dystonia and adolescent-onset super-refractory myoclonic status epilepticus contributing to strikingly rapid and progressive cortical atrophy and death.
BACKGROUND: The dynamin 1-like gene ( DNM1L) encodes a GTPase that mediates mitochondrial and peroxisomal fission and fusion. We report a new clinical presentation associated with a DNM1L pathogenic variant and review the literature. RESULTS: A 13-year-old boy with mild developmental delays and paroxysmal dystonia presented acutely with multifocal myoclonic super-refractory status epilepticus. Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy. Rapid trio-whole exome sequencing revealed a de novo heterozygous c.1207C>T (p.R403C) pathogenic variant in DNM1L. Immunofluorescence staining of fibroblast mitochondria revealed abnormally elongated and tubular morphology. CONCLUSIONS: This case highlights the diagnostic importance of rapid whole exome sequencing within a critical care setting and reveals the expanding phenotypic spectrum associated with DNM1L variants. This now includes progressive paroxysmal dystonia and adolescent-onset super-refractory myoclonic status epilepticus contributing to strikingly rapid and progressive cortical atrophy and death.
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