Marked Improvement after Globus Pallidus Deep Brain Stimulation in Dystonia-24 with a Novel ANO3 Variant: A Case Report and Literature Review

Running title: GPi-DBS for DYT24 and Novel ANO3 Mutation Dystonia-24 (DYT-24, previously known as DYT-ANO3) is a rare autosomal dominant movement disorder caused by mutation in the anoctamin 3 (ANO3) gene, often presenting with craniocervical involvement. 1 Pharmacological interventions and botulinum toxin injections are conventional management strategies; however, DYT-24 frequently shows marked resistance to these conservative therapies, necessitating more invasive neuromodulation. [1][2]2][3][4][5][6][7] Although a few studies have suggested the efficacy of deep brain stimulation (DBS), detailed clinical outcomes remain limited. [1][2]2][3][4][5][6][7] Here, we report a Japanese man with DYT-24 in whom genetic testing identified a novel ANO3 variant (c.1705G>T, p.V569L), and who showed marked clinical improvement after GPi-DBS.A 53-year-old man was admitted to our department with progressively worsening dystonic symptoms.At the age of 18 years, the patient first presented with craniocervical dystonia, without significant interference in daily activities.At 45 years of age, the patient developed oral dystonia, resulting in dysarthria.At the age of 51 years, the patient was referred to another neurology clinic because of truncal flexion, which prompted him to LETTER TO THE EDITOR transition from working in the foundry industry to employment as a forklift driver.Pharmacological therapy, including trihexylphenidyl, clonazepam, tizanidine hydrochloride, and diazepam, was initiated along with botulinum injections; however, these treatments were ineffective.Family history suggested that his father, who had passed away, exhibited similar symptoms of craniocervical dystonia and dysarthria but did not seek medical attention.The patient had no contact with his paternal relatives, and detailed information regarding the paternal family history was unavailable.No history of consanguinity existed.On admission, neurological examination revealed generalized dystonia, including craniocervical dystonia, blepharospasm, oral dystonia, dystonia of both upper limbs and the trunk, and tremor in both upper limbs.Dystonia of the neck and bilateral upper limbs worsened during walking (Video 1).Blood and cerebrospinal fluid analyses were normal.Magnetic resonance imaging and single-photon emission computed tomography findings were unremarkable.Considering the positive family history, early onset, and generalized dystonia with predominant craniocervical involvement, an inherited form of dystonia was suspected.Genetic analysis identified a novel ANO3 variant (c.1705G>T, p.V569L), classified as a variant of uncertain significance according to ACMG/AMP criteria.At 53 years of age,