Epilepsy Phenotypic Spectrum of NUS1-Related Disorder: A Case Series

Area of Science:

• Genetics
• Neurology
• Epilepsy Research

Background:

• Epilepsy with myoclonic and atonic seizures (EMAtS), or Doose syndrome, is a rare childhood epilepsy.
• The NUS1 gene, encoding Nogo-B receptor (NgBR), plays a role in cholesterol biosynthesis.
• Pathogenic NUS1 variants are linked to movement disorders and epilepsy, but their epilepsy spectrum and EEG phenotype are not fully understood.

Purpose of the Study:

• To characterize the epilepsy and EEG phenotype in patients with NUS1-related disorder.
• To investigate the association between NUS1 variants and specific epilepsy syndromes like EMAtS.

Main Methods:

• A single-center case series of five patients with NUS1-related disorder was analyzed.
• Clinical data, epilepsy diagnosis, genetic variants, and EEG findings were reviewed.

Main Results:

• Three patients met EMAtS criteria; others had milder generalized epilepsy.
• Four patients had pathogenic NUS1 variants, one had a variant of unclear significance.
• Patients presented with normal to mild developmental delay, normal brain MRIs, and seizure onset between 1-7 years.
• EEG revealed generalized spike-wave discharges and a consistent pattern of invariant monomorphic theta activity in four patients.
• Seizures responded well to levetiracetam and/or valproic acid.

Conclusions:

• NUS1 variants are associated with a generalized epilepsy phenotype.
• An invariant EEG pattern of monomorphic theta activity is characteristic of NUS1-related epilepsy.