To describe a case of immune responsive new onset refractory status epilepticus in a post-partum TBC1D24 variant carrier.

TBC1D24 variants demonstrate marked phenotypic-pleiotropy including DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures), intellectual disability, developmental and epileptic encephalopathy, multifocal myoclonus or epilepsia partialis continua, with ictal events often triggered by fatigue or febrile episodes.  

Case report and review of literature.

A 32-year-old woman presented at day 15 post-partum with status epilepticus refractory to multiple anti-seizure medications (Levetiracetam, Lacosamide, Phenytoin, Phenobarbital, Clobazam). MRI brain showed cerebellar atrophy and extensive cerebellar high signal without clinical correlate. EEG captured complex focal hypermotor seizure, beginning in the right central parietal region, then evolving to involve bilateral parietal regions, with later bifrontal involvement. Seizure control was achieved with initiation of a 5-day course of high-dose parenteral corticosteroids and intravenous immunoglobulin, but extensive autoimmune investigations did not reveal any abnormal findings.   

Additional history revealed intermittent episodes of focal myoclonus involving her right upper limb since infanthood, with no prior response to Levetiracetam, Lamotrigine, Carbamazepine and Sodium Valproate. Multiple prior EEGs were normal, with bursts of sharp waves from left hemisphere evident on one occasion. Genetic testing revealed a homozygous likely pathogenic TBC1D24 gene variant (c.680G>A; p.Arg227Gln), without evidence of other associated cognitive, auditory or cutaneous features.

This case demonstrates a novel presentation of familial epilepsy with variable foci associated with TBC1D24 c.680G>A variant. This variant has been reported in one other non-related heterozygous carrier who presented in infanthood with prolonged tonic-clonic seizures during febrile episodes. While this individual showed a dramatic improvement in seizure control associated with less frequent febrile episodes, no prior response to immunomodulatory therapies have been previously described in TBC1D24 variants.