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

9 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 Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy.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)
Pages (from-to)651-658
Number of pages8
JournalJournal of child neurology
Volume33
Issue number10
DOIs
StatePublished - Sep 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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