NUS1 Exon 2 Deletion: A Crossover Between Epilepsy and Movement Disorders (P12-1.009)

Abstract

<h3>Objective:</h3> We present two cases of patients presenting with epilepsy and a concomitant movement disorder found to have a heterozygous pathogenic variant in NUS1 with a deletion in exon 2. <h3>Background:</h3> The NUS1 gene is associated with autosomal dominant developmental and epileptic encephalopathy. Movement disorders such as tremor, ataxia, and myoclonus have been reported, though this clinical phenotype is not well defined. <h3>Design/Methods:</h3> Case Series <h3>Results:</h3> <h3>Case 1:</h3> A 54-year-old man with a history of schizophrenia and moderate intellectual disability presented to Movement Disorders Clinic with debilitating ataxia and multifocal myoclonus involving limbs and facial muscles and to Epilepsy Clinic for generalized epilepsy. Seizure semiology was generalized tonic-clonic. The patient’s father reportedly had tremor and seizures; however, patient was under guardianship of a caregiver with limited familial information. MRI brain was unremarkable. EEG captured myoclonic jerks without a cortical correlate. Seizures were well controlled on Keppra and Depakote. <h3>Case 2:</h3> A 25-year-old woman presented to Epilepsy Clinic for Lennox Gastaut Syndrome and to Movement Disorders Clinic for an action tremor with action-induced myoclonus. Epilepsy started at age 2 and was refractory shortly after onset with concurrent global developmental delay. Seizure semiologies included atonic, clonic, absence, and generalized tonic-clonic. Her epilepsy was well controlled on Epidiolex, lamotrigine, and clobazam. MRI brain was unremarkable. Interictal EEG showed background slowing, paroxysmal beta frequency activities, and generalized slow spike and wave discharges. Depakote was previously weaned with no improvement in tremor or myoclonus. A genetic panel (INVITAE™) revealed a heterozygous pathogenic variant in NUS1 with a deletion in exon 2 in both cases. <h3>Conclusions:</h3> Despite epilepsy being well controlled, our cases had an ongoing debilitating movement disorders. In patients with epilepsy who present with subcortical myoclonus, ataxia, or tremor, a genetic panel should be considered as well as referral to Movement Disorders for interdisciplinary management. <b>Disclosure:</b> Dr. Terpak has nothing to disclose. Dr. Schuck has nothing to disclose. Dr. Culpepper has nothing to disclose. Dr. Shneyder has nothing to disclose. Dr. Krishnaiengar has nothing to disclose. Dr. Zarroli has nothing to disclose.