VPS16-related dystonia is an autosomal dominant neurological condition characterized by manifestation of dystonic features in one or more parts of the body; the most common type of dystonia observed in the context of heterozygous pathogenic VPS16 variants is a progressive early-onset dystonia (median age at onset 12 years, range 3-50 years), with prominent oromandibular, bulbar, cervical, and upper limb involvement. Most affected individuals develop generalized dystonia over time, but only a minority of cases were found to lose the ability to walk. Additional clinical symptoms may include mild-to-moderate intellectual impairment and neuropsychiatric features. Brain MR imaging can reveal symmetrical signal changes of the basal ganglia reminiscent of brain iron accumulation in some patients. There is marked intra- and interfamilial heterogeneity in clinical presentations and disease penetrance. Generally, VPS16-related dystonia can be regarded as a condition with incomplete penetrance, although exact penetrance estimates have not yet been determined. The prevalence of the condition remains currently unknown, but VPS16 variants appear to account for a substantial number of monogenic subtypes in larger isolated dystonia cohorts.
VPS16