Objective: To describe a rare case of NUS1 gene mutation related progressive epilepsy myoclonus ataxia syndrome.

Background: Pathogenic variants of NUS1 gene have been associated with multiple cases of progressive myoclonic epilepsy and/or Myoclonus ataxia syndromes. Recessive pathogenic variants of this gene were first described in two siblings presenting with a congenital defect of glycosylation. Patients can present with a spectrum of symptoms ranging from psychomotor retardation, epilepsy, cerebellar ataxia, cortical myoclonus.

Method: We report a case of 25-year-old woman who presented with gradual progression of myoclonus and ataxia. Her history was significant for intellectual disability, primary generalized epilepsy, and psoriatic arthritis. Examination was consistent with positive and negative multifocal myoclonus and gait ataxia. Her presentation was initially attributed to use of methotrexate for psoriasis and was discontinued without any improvement. Her interictal EEG was consistent with bursts of high-amplitude sharply contoured waves at 2.5 Hz per second, associated with small spikes, more prominent in bilateral frontal region, lasting for 3-6 seconds without any clinical correlate. Her myoclonus had no EEG correlate and was thought to be sub-cortical in origin. Further extensive workup with MRI brain, EMG/NCS, Pyruvate, lactate and Anti-folate receptor testing were all negative.

Results: A step wise focused genetic workup has been undertaken and her FLOR1 gene sequencing, epilepsy gene panel and progressive myoclonic epilepsy gene panel were positive for variants of unknown significance. A subsequent whole genome sequencing was positive for de novo pathogenic variant of NUS1:c.571del (p.L191Cfs*11). Valproic acid and levetiracetam failed to suppress her myoclonus. She had symptomatic relief of her myoclonus with clonazepam

Conclusion: There are less than 25 reported cases of NUS1 pathogenic variant associated with myoclonus, epilepsy, ataxia, intellectual disability syndrome (MEAID syndrome) till date. NUS1 gene was not included as part of proband testing until recently, so we wanted to emphasize through this case that NUS1 gene testing should be included in the genetic screening of undiagnosed phenotypes of myoclonus, myoclonus-ataxia, and progressive myoclonus epilepsy.

References: Riboldi, G. M., Monfrini, E., Stahl, C., & Frucht, S. J. (2022). NUS1 and Epilepsy-myoclonus-ataxia Syndrome: An Under-recognized Entity?. Tremor and other hyperkinetic movements (New York, N.Y.), 12, 21. https://doi.org/10.5334/tohm.696

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MDS Abstracts - https://www.mdsabstracts.org/abstract/progressive-myoclonic-epilepsy-ataxia-syndrome-associated-with-nus1-gene-mutation/