Case series: NUS1 deletions cause a progressive myoclonic epilepsy with ataxia

<h3>Background</h3> <i>NUS1</i> gene mutations result in a neurological disorder which encompasses developmental encephalopathy and epilepsy, and congenital disorders of glycosylation. So far, 19 patients with <i>NUS1</i> deletions have been reported that display varying phenotypical features including epilepsy, intellectual disability, and myoclonus. <h3>Case Presentation</h3> We report a patient with a novel heterozygous 5.0 Mb deletion in the region 6q22.1q22.31 involving the <i>NUS1</i> gene. We present clinical information with EEG, MRI and video. Along with the 19 reported patients, we identified 37 other <i>NUS1</i> variants through ClinVar, of which 25 are genetically similar and 15 of these have sufficient clinical data. Our patient presented with features of progressive myoclonic tremor, generalised absence and tonic-clonic seizures, intellectual disability, and cerebellar ataxia, which overlaps with the case series we present. <h3>Conclusion</h3> The identification of <i>NUS1</i> gene deletion disorder does not lead to a change in treatment but predicts a progressive clinical trajectory. Recognition of this helps differentiate neurological progression from the impact of anti-seizure medicine. We also describe novel features of psychosis, spasticity, and sleep behaviour abnormalities and suggest that these may also be due to the <i>NUS1</i> deletion, expanding the literature that exists on the phenotype of this very rare genetic disorder.