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MINI REVIEW article

Front. Neurosci.

Sec. Neurogenomics

This article is part of the Research TopicAdvances in epilepsy research: exploring biomarkers, brain stimulation, and neurosurgical interventions - Volume IIView all 3 articles

Novel NPRL3 variant associated with Sleep-Related Hypermotor Epilepsy - a case report and educational review

Provisionally accepted
Serena BroggiSerena Broggi1*Kai-Nicolas PoppertKai-Nicolas Poppert2Matthias MauritzMatthias Mauritz2Gudrun KalssGudrun Kalss2Markus LeitingerMarkus Leitinger2Angela AbichtAngela Abicht3,4Eugen TrinkaEugen Trinka2Fabio RossiniFabio Rossini2,5
  • 1Neurology and Stroke Unit, ASST Sette Laghi, Varese, Italy, Varese, Italy
  • 2Uniklinikum Salzburg - Christian-Doppler-Klinik, Salzburg, Austria
  • 3Medizinisch Genetisches Zentrum, Munich, Germany
  • 4LMU Klinikum Friedrich-Baur-Institut, Munich, Germany
  • 5UMIT TIROL Private Universitat fur Gesundheitswissenschaften und -technologie GmbH, Hall in Tirol, Austria

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Introduction: Sleep-related hypermotor epilepsy (SHE) is a rare epilepsy syndrome characterized by nocturnal seizures that predominantly arise from sleep, featuring complex motor behaviours. Pathogenic variants in the NPRL3 gene and other regulators of the mTOR pathway have been linked to diverse epilepsy phenotypes, including SHE. SHE is challenging to diagnose due to its diverse presentations, overlap with non-epileptic sleep disorders and semiological similarities with functional/dissociative seizures (FDS). Case Report: We present the case of a 61-year-old woman with a lifelong history of nocturnal paroxysmal events and focal epilepsy. She experienced stereotyped nocturnal episodes of focal motor seizures with retained consciousness, hyperkinetic, with asymmetric posturing. Despite multiple antiseizure medications (ASMs), only carbamazepine (CBZ) provided long-term seizure freedom. Genetic testing revealed a novel heterozygous mutation in the NPRL3 gene. Discussion: This case highlights the diagnostic challenges of SHE and the importance of genetic testing in drug-resistant epilepsy. The identified NPRL3 mutation underscores the genetic complexity of SHE and its implications for treatment.

Keywords: Paroxysmal nocturnal dystonia, Nocturnal seizures, Nocturnal frontal lobe epilepsy, Personalised medicine, mTOR, Hyperkinetic seizure

Received: 09 Aug 2025; Accepted: 24 Nov 2025.

Copyright: © 2025 Broggi, Poppert, Mauritz, Kalss, Leitinger, Abicht, Trinka and Rossini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Serena Broggi

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material