[Case report: VPS16 - a new cause of generalized dystonia]

Introduction - Dystonia is the third most common movement disorder, which is highly diverse, both clinically and genetically. With the rise of next-generation sequencing, the number of genes associated with dystonia is increasing. Genetic testing is particularly important to predict the effectiveness of widely used therapeutic approaches (e.g., deep brain stimulation/DBS).Case report - The symptoms of a 69-yearold female patient began at the age of 18 years. Her symptoms developed gradually, i.e., cervical abnormal postures and movements first, followed by tongue movement problems, writer's cramp and speech difficulty. At the age of 38, she became severely disabled. During the neurological examination, generalized dystonia as well as occasional choreoathetoid movement elements on the upper limbs were observed. We noticed dysphagia, dysarthria and occasional oro-facial and cervical dyskinesia. Brain magnetic resonance imaging demonstrated minimal cortical atrophy. The whole exome sequencing analysis detected a heterozygous pathogenic nonsense mutation in the VPS16 gene. The patient is currently receiving clonazepam therapy with moderate symptom relief. Trihexyphenidyl treatment has not been attempted because the significant side effects of the previously tried anticholinergic drug. Although DBS was offered, the patient refused this treatment.Conclusion - Dystonia caused by mutation of the VPS16 gene (autosomal dominant) is a recently recognized new form of hereditary dystonia. The disease is characterized by early-onset progressive, generalized dystonia, with the predominant involvement of orofacial, bulbar, cervical and upper limb regions. Currently there is no clear recommendation for treatment, however, beneficial effects of DBS as well as botulinum toxin have been reported.