NUS1 Variants Lead to Epilepsy with Myoclonic Atonic Seizures
Abstract number :
1.536
Submission category :
18. Case Studies
Year :
2024
Submission ID :
1393
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Saumel Ahmadi, MD, PhD – Washington University in St Louis
Natalie Fulton, BA – Washington University in St Louis
Michael Morrissey, PhD – Washington University in St Louis
Rebekah Landre, MS – Washington University in St Louis
Stuart Tomko, MD – Washington University in St Louis
Fumihiko Urano, MD, PhD – Washington University in St Louis
Réjean Guerriero, DO – Washington University in St Louis
Rationale: Epilepsy with myoclonic and atonic seizures (EMAts), also known as Doose syndrome, accounts for 1-2% of childhood epilepsies, and various genes have been implicated in causing this epilepsy syndrome. NUS1 gene encodes for Nogo-B receptor (NgBR) which stabilizes the dehydrodolichyl-diphosphate synthase complex in the endoplasmic reticulum, promoting its enzymatic activity (cis-IPTase) and thereby regulating cholesterol biosynthesis. Pathogenic variants in NUS1 have been associated with movement disorder and/or epilepsy, however the spectrum of epilepsy and EEG phenotype has not been described.
Methods: This is a single center case series where we identified 5 patients with NUS1 gene variants, and also had a diagnosis of epilepsy. Four of these patients had a pathogenic variant in NUS1, and one patient had a VUS. We did clinical, imaging and EEG characterization of these patients.
Results: All patients bearing the pathogenic variants in NUS1 had developmental delay with a normal brain MRI. Age of seizure onset in these patients was 1-7 years, and patients responded to levetiracetam. The EEG findings for these patients included presence of spike and slow wave discharges, as well as presence of abundant generalized invariant monomorphic theta range activity, which was seen in 4 out of the 5 patients.
Conclusions: NUS1 gene variants are associated with a Doose Syndrome phenotype, characterized by myoclonic and atonic seizures and an invariant EEG pattern.
Funding: NIH T32: 5T32GM139799-04
Case Studies