De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus. (September 2018)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Journal of child neurology. Volume 33:Number 10(2018:Oct.)
• Page Start: 651
• Page End: 658
• Publication Date: 2018-09
• Subjects: mitochondrial disease -- paroxysmal dyskinesia -- rapid whole exome sequencing -- refractory status epilepticus; Nervous system -- Diseases -- Periodicals; 618.928
• DOI: 10.1177/0883073818778203
• Languages: English
• ISSNs: 0883-0738

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 Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy.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