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 Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy.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 language | English (US) |
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Pages (from-to) | 651-658 |
Number of pages | 8 |
Journal | Journal of child neurology |
Volume | 33 |
Issue number | 10 |
DOIs | |
State | Published - 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