De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus

Conor S. Ryan, Anthony L. Fine, Alexander L. Cohen, Brenda M. Schiltz, Deborah L. Renaud, Elaine C Wirrell, Marc C. Patterson, Nicole J. Boczek, Raymond Liu, Dusica Babovic-Vuksanovic, David C. Chan, Eric T. Payne

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy.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.

Original languageEnglish (US)
JournalJournal of Child Neurology
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • mitochondrial disease
  • paroxysmal dyskinesia
  • rapid whole exome sequencing
  • refractory status epilepticus

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

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