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

Ryan, Conor S. and Fine, Anthony L. and Cohen, Alexander L. and Schiltz, Brenda M. and Renaud, Deborah L. and Wirrell, Elaine C. and Patterson, Marc C. and Boczek, Nicole J. and Liu, Raymond and Babovic-Vuksanovic, Dusica and Chan, David C. and Payne, Eric T. (2018) De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus. Journal of Child Neurology, 33 (10). pp. 651-658. ISSN 0883-0738. http://resolver.caltech.edu/CaltechAUTHORS:20180611-081026318

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 Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy.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


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1177/0883073818778203DOIArticle
ORCID:
AuthorORCID
Ryan, Conor S.0000-0001-5400-3715
Cohen, Alexander L.0000-0001-6557-5866
Additional Information:© 2018 by SAGE Publications. Received: January 03, 2018; Revisions received: April 25, 2018; Accepted: April 30, 2018, First Published June 7, 2018.
Subject Keywords:mitochondrial disease, paroxysmal dyskinesia, rapid whole exome sequencing, refractory status epilepticus
Record Number:CaltechAUTHORS:20180611-081026318
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20180611-081026318
Official Citation:De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus. Conor S. Ryan, MD, Anthony L. Fine, MD, Alexander L. Cohen, MD, PhD, Brenda M. Schiltz, MD, Deborah L. Renaud, MD, Elaine C. Wirrell, MD, Marc C. Patterson, MD, Nicole J. Boczek, PhD, Raymond Liu, PhD, Dusica Babovic-Vuksanovic, MD, David C. Chan, MD, PhD, and Eric T. Payne, MD. Journal of Child Neurology. Vol 33, Issue 10, pp. 651 - 658. First Published June 7, 2018. https://doi.org/10.1177/0883073818778203
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:86957
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:11 Jun 2018 21:02
Last Modified:13 Aug 2018 23:29

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