Dominant VPS16 Pathogenic Variants: Not Only Isolated Dystonia

Mov Disord Clin Pract. 2024 Jan;11(1):87-93. doi: 10.1002/mdc3.13927. Epub 2023 Dec 12.

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.

Keywords: GPi-DBS; HOPSANDs; choreoathetosis; freezing; myoclonus; pharyngeal spasm.

Publication types

  • Case Reports

MeSH terms

  • Deep Brain Stimulation* / methods
  • Dystonia* / diagnosis
  • Dystonic Disorders* / diagnosis
  • Gait Disorders, Neurologic*
  • Humans
  • Parkinson Disease*
  • Vesicular Transport Proteins

Substances

  • VPS16 protein, human
  • Vesicular Transport Proteins