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 journalArticle

3 Citations (Scopus)

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 Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy.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

Fingerprint

Dynamin I
Dystonia
Status Epilepticus
Exome
Genes
Atrophy
Mitochondrial Dynamics
GTP Phosphohydrolases
Critical Care
Fluorescent Antibody Technique
Mitochondria
Seizures
Fibroblasts
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus. / Ryan, Conor S.; Fine, Anthony L.; Cohen, Alexander L.; Schiltz, Brenda M.; Renaud, Deborah L.; Wirrell, Elaine C; Patterson, Marc C.; Boczek, Nicole J.; Liu, Raymond; Babovic-Vuksanovic, Dusica; Chan, David C.; Payne, Eric T.

In: Journal of Child Neurology, 01.01.2018.

Research output: Contribution to journalArticle

Ryan, Conor S. ; Fine, Anthony L. ; Cohen, Alexander L. ; Schiltz, Brenda M. ; Renaud, Deborah L. ; Wirrell, Elaine C ; Patterson, Marc C. ; Boczek, Nicole J. ; Liu, Raymond ; Babovic-Vuksanovic, Dusica ; Chan, David C. ; Payne, Eric T. / De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus. In: Journal of Child Neurology. 2018.
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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.",
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AU - Renaud, Deborah L.

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AU - Patterson, Marc C.

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