Dominant <scp><i>VPS16</i></scp> Pathogenic Variants: Not Only Isolated Dystonia
Edoardo Monfrini, Laura Avanzino, Giovanni Palermo, Giulia Bonato, Gloria Brescia, Roberto Ceravolo, Giovanna Cantarella, Paola Mandich, Holger Prokisch, Karin Storm van’s Gravesande, Giulia Straccia, Antonio Emanuele Elia, Chiara Reale, Celeste Panteghini, Giovanna Zorzi, Roberto Eleopra, Roberto Erro, Miryam Carecchio, Barbara Garavaglia, Michael Zech, Luigi Romito, Alessio Di Fonzo
Abstract
BACKGROUND: VPS16 pathogenic variants have been recently associated with inherited dystonia. Most patients affected by dominant VPS16-related disease display early-onset isolated dystonia with prominent oromandibular, bulbar, cervical, and upper limb involvement, followed by slowly progressive generalization. CASES: We describe six newly reported dystonic patients carrying VPS16 mutations displaying unusual phenotypic features in addition to dystonia, such as myoclonus, choreoathetosis, pharyngospasm and freezing of gait. Response to bilateral Globus Pallidus Internus Deep Brain Stimulation (GPi-DBS) is reported in three of them, associated with significant improvement of dystonia but only minor effect on other hyperkinetic movements. Moreover, five novel pathogenic/likely pathogenic variants are described. CONCLUSIONS: This case collection expands the genetic and clinical spectrum of VPS16-related disease, prompting movement disorder specialists to suspect mutations of this gene not only in patients with isolated dystonia.