Objective: To provide a description of a young patient with atypical onset and presentation of rare DYT30-VPS16 dystonia.

Background: To date, 44 patients from 31 families with DYT-VPS16 and have been reported. Onset of dystonia was classically in childhood or young adulthood with a focal onset [1,2].

Method: Clinical description and laboratory testing.

Results: We saw a 20-year-old patient who could only walk with assistance, had impaired fine motor skills and significant difficulties with self-care. He exhibited mild dystonia in the arms and legs when walking, with severe speech impairment, short-term memory impairment, and mild episodes of urinary incontinence.

The birth was on time, with double umbilical cord entanglement. At birth, his feet were deformed and the hands were clenched. Head MRI was normal at birth. He started talking and walking at age 5. A variety of orthopedic surgeries were performed on his hands and feet. His walking had worsened in the last 2 years.

On examination: myopia, astigmatism, partial atrophy of the optic nerves of both eyes. He had severe dysarthria. Masking of facies and mild bradykinesia as seen in the arms and legs. There was no tremor. Muscle power was decreased in the distal parts of the legs with severe atrophy of the muscles of the lower legs and feet. He walked only with support, and had a dystonic posture of the legs and arms. At rest, dystonic posturing of the feet and hands was seen. He had severe deformation of the hands and feet (fig.1).

A trial of 250 mg of levodopa t.i.d. did not provide any effect.

History on the paternal side was unknown (his father reportedly had “disabling disease”).

EMG showed severe axonopathy of the peripheral nerves of both legs. Brain MRI showed signs of developmental anomalies of the corpus callosum in the form of hypoplasia of its posterior sections. Exome sequencing showed a likely pathogenic heterozygous canonical splice-site variant in VPS16. His mother did not carry the variant.

Conclusion: In addition to the more typical features of VPS16 dystonia including generalized dystonia, peripheral neuropathy and dysarthria, this patient exhibited camptodactyly and foot deformities, partial atrophy of the optic nerves and anomaly of the corpus callosum. This could represent expansion of the VPS16 phenotype. At the same time, the patient had hypoxic injury at birth and was born with bone anomalies, which significantly affected his cognitive and motor functions, including walking.

Congenital camptodactyly of the long fingers

References: 1. Desjardins, C., Delorme, C., Méneret, A., Flamand, C., Leveque, N., De Sainte Agathe, J. M., … & Vidailhet, M. (2024). A Novel Pattern of Dystonia in DYT-VPS16: “Speaking in Tongues”. Neurology: Genetics, 10(4), e200154.
2. Steel, D., Zech, M., Zhao, C., Barwick, K. E., Burke, D., Demailly, D., … & Genomics England Research Consortium. (2020). Loss‐of‐function variants in HOPS complex genes VPS16 and VPS41 cause early onset dystonia associated with lysosomal abnormalities. Annals of neurology, 88(5), 867-877.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/atypical-onset-and-presentation-of-rare-dyt30-vps16-dystonia/