VPS13D Movement Disorder

Clinical characteristics: VPS13D movement disorder is a hyperkinetic movement disorder (dystonia, chorea, and/or ataxia) of variable age of onset that can be associated with developmental delay. Onset ranges from birth to adulthood. Individuals can present in childhood with motor delays and gait instability. Cognitive impairment ranging from mild intellectual disability to developmental delay has been reported, and several individuals have normal cognitive function. Individuals have also presented as young adults with gait difficulties caused by spastic ataxia or ataxia. In addition to gait ataxia, affected individuals had limb ataxia, dysarthria, and eye movement abnormalities (macro-saccadic oscillations, nystagmus, and saccadic pursuit). Additional features reported in some individuals include peripheral neuropathy and/or seizures. The disorder progresses to spastic ataxia or generalized dystonia, which can lead to loss of independent ambulation.

Diagnosis: The diagnosis of VPS13D movement disorder is established in a proband by identification of biallelic pathogenic variants in VPS13D on molecular genetic testing.

Management: Treatment of manifestations: Standard treatment for seizures; spasticity treatments include baclofen, tizanidine, benzodiazepines, dantrolene sodium, gabapentin, botulinum toxin injections, and intrathecal baclofen; treatment options for dystonia include trihexyphenidyl, botulinum toxin injections, benzodiazepines, baclofen, and levodopa. A multidisciplinary team including occupational and physical therapists and a physiatrist is important; supportive developmental therapies should be provided as needed.

Surveillance: Monitor for urinary urgency, contractures, and seizures; evaluate fall risk and gait stability; monitor developmental progress and educational needs.

Genetic counseling: VPS13D movement disorder is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for a pregnancy at increased risk are possible if the VPS13D pathogenic variants in the family are known.