An 8-year-old boy with generalized myoclonic epilepsy followed by progressive cognitive decline presented with worsening myoclonus despite being compliant with prescribed clobazam. The movements (Video 1) in conjunction with a worsening cognitive status over time were concerning for a progressive myoclonic epilepsy. Initial EEG captured frequent myoclonic seizures time-locked with spike-wave activity (Figure). Overnight EEG revealed normal sleep architecture. His seizures stopped with valproic acid load. Genetic testing revealed a heterozygous pathogenic variant in NEXMIF (c.2478_2479dup), which is associated with NEXMIF encephalopathy. NEXMIF encephalopathy is characterized by mild to severe intellectual disability and includes myoclonic seizures, absence seizures, and atonic seizures.1
Figure. Longitudinal Bipolar Montage EEG With Diffuse Spike Wave Associated With Myoclonus.
Video of myoclonus.Download Supplementary Video 1 (4.7MB, mov) via http://dx.doi.org/10.1212/201722_Video_1
Traditionally, the differential diagnosis of progressive myoclonic epilepsy entails diseases such as Lafora body disease, Unverricht-Lundbord disease, NCL, type 1 sialidosis, and MERRF.2 This case emphasizes the consideration of NEXMIF variants in the differential diagnosis of a suspected progressive myoclonic epilepsy.
Supplementary Material
Appendix. Authors
Author Contributions
L.E. Chorny and D.R. Nordli: drafting/revision of the article for content, including medical writing for content; major role in the acquisition of data; literature review. F. Galan: drafting/revision of the article for content, including medical writing for content.
Study Funding
The authors report no targeted funding.
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References
- 1.Stamberger H, Hammer TB, Gardella E, et al. , NEXMIF encephalopathy: an X-linked disorder with male and female phenotypic patterns. Genet Med. 2021;23(2):363-373. doi: 10.1038/s41436-020-00988-9 [DOI] [PubMed] [Google Scholar]
- 2.Girard JM, Turnbull J, Ramachandran N, Minassian BA. Progressive myoclonus epilepsy. Handbook Clin Neurol. 2013;113:1731-1736. doi: 10.1016/b978-0-444-59565-2.00043-5 [DOI] [PubMed] [Google Scholar]
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Supplementary Materials
Video of myoclonus.Download Supplementary Video 1 (4.7MB, mov) via http://dx.doi.org/10.1212/201722_Video_1