Abstracts

Rationale: The dynamin 1-like (DNM1L) gene encodes a member of the dynamin superfamily of GTPases which mediates mitochondrial and peroxisomal fission. Mutations are reported in a neonate with a lethal encephalopathy and in a few infants and children with refractory status epilepticus. We report a new clinical presentation associated with a DNM1L pathogenic mutation. Methods: Case report. Results: A 13 year old boy with mild developmental delays and exercise-induced, paroxysmal limb "dystonia" was evaluated in the outpatient neurology clinic. Investigations revealed a normal brain MRI, mildly low CSF serotonin and dopamine metabolites, and generalized EEG epileptiform discharges. Improvement was noted with levodopa-carbidopa and levetiracetam. One year later, he presented with myoclonic status epilepticus refractory to levetiracetam, piracetam, fosphenytoin, phenobarbital, lacosamide, topiramate, felbamate, and high-dose midazolam and pentobarbital infusions. He developed propylene glycol toxicity secondary to pentobarbital and was transitioned to inhaled isoflurane. Continuous EEG monitoring confirmed a suppression-burst pattern with high-amplitude (1-4Hz) generalized polyspike and wave discharges, often associated with clinical myoclonus (bilateral face and limbs), and focal subclinical seizures. A ketamine infusion, ketogenic diet, methylprednisolone, allopregnanolone, and anakinra were unsuccessful. Trio-based whole exome sequencing revealed a de novo heterozygous c.1207C>T (p.R403C) pathogenic variant of the DNM1L gene. He remained in a high dose phenobarbital (enteral) coma with intermittent clinical myoclonus for several weeks until care was withdrawn. Conclusions: Our case highlights the diagnostic importance of whole exome sequencing and reveals that the current phenotypic spectrum associated with DNM1L mutations is expanding but includes varying degrees of cognitive impairment and refractory epilepsy. Funding: None.