Objective: To report a case of generalized dystonia with a genetic variant in VPS16 gene, possibly related to AD dystonia 30.

Background: Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal movements, postures, or both.  Etiologies are heterogeneous. Despite the fact that more than 250 genes have been associated to dystonia, most patients remain undiagnosed after comprehensive examination.  Recently, novel pathogenic variants in new genes have been described. One of them is VPS16. Its genetic variants are considered the most frequent novel cause of isolated dystonia and are related to dystonia 30 (DYT 30).

Method: We report a 44-year-old female patient who began with a patterned abnormal movement of the right upper limb at age 38. Dystonia progressed over the years to the neck, the trunk, left upper limb and lower limbs. She referred difficulty writing since childhood. Past medical records were not noteworthy. Her current neurological exam shows generalized dystonia with retrocollis, laterocollis to the left and torticollis to the right and dystonic posture of both hands with a twisting movement of the right arm. When walking, there is an inward rotation of both feet. Attention deficit disorder was found. The family history was unremarkable, except for the eldest daughter who states slight tremor when writing.

Results: Routine blood testing and brain MRI were normal. Cervical MRI revealed mild discopathies. Pharmacologic treatment with levodopa elicited a mild benefit. Botulinum toxin injections in the cervical muscles had a good outcome.  Genetic testing for the most frequent forms of dystonia were negative.  In the exome sequencing study a genetic variant was detected in the VPS16 gene (NM_0225753.3:c.2375+1G>T). This variant is thought to disrupt a highly-conserved donor splicing site related to non stop decay, giving more relevance to this finding.

Family segregation studies are ongoing.

Conclusion: For phenotype-genotype correlations, rare variants of unknown clinical significance need to be identified in similarly affected patients and/or supportive functional or segregation studies are required. The relevance of our case is that of trying to help outline the clinical phenotype of VPS-related dystonia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-variant-in-the-vps16-gene-in-a-44-year-old-patient-with-generalized-dystonia/