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Review
. 2025 Sep 19.
doi: 10.1002/mdc3.70362. Online ahead of print.

VPS16-Related Dystonia: Expanding the Clinical Spectrum and Therapeutic Insights

Baikuntha Panigrahi  1 , Divya Madathiparambil Radhakrishnan  2 , Arti Saini  2 , Divyani Garg  2 , Chaitra Rajanna  2 , Aminu Aliyar  3 , Govinda Siripurapu  4 , Animesh Das  2 , A Elavarasi  2 , Ayush Agarwal  2 , Anu Gupta  2 , Awadh Kishor Pandit  2 , Venugopalan Yamuna Vishnu  2 , Mamta Bhushan Singh  2 , Rohit Bhatia  2 , Rajinder Kumar  5 , Achal Kumar Srivastava  2 , Roopa Rajan  2
Affiliations
Review

VPS16-Related Dystonia: Expanding the Clinical Spectrum and Therapeutic Insights

Baikuntha Panigrahi et al. Mov Disord Clin Pract. .

Abstract

Background: DYT-VPS16 is a rare monogenic form of dystonia caused by pathogenic variants in the vacuolar protein sorting 16 homolog (VPS16) gene. Although increasingly recognized, the clinical spectrum and therapeutic responsiveness, particularly to deep brain stimulation (DBS), remain incompletely defined.

Cases: We report six affected individuals (5 males, 1 female) from five unrelated Indian families harboring VPS16 variants. The median age at onset was 16.5 years (range, 8-18 years). Dystonia began in the cervical (n = 2), upper limb (n = 2), or laryngeal (n= 2) regions. Additional features included tremor (n = 2) and sleep disturbances (n = 1).

Literature review: A structured literature review identified 34 previously reported DYT-VPS16 cases treated with DBS. Pooled analysis revealed a responder rate (defined as ≥30% improvement in BFMDRS-M) of 0.57 (95% CI: 0.31-0.81; I2 = 22.9%) suggesting a favorable therapeutic response in this subgroup.

Conclusion: Our findings broaden the genotypic and phenotypic landscape of DYT-VPS16, suggesting a more motor-predominant and potentially milder expression in South Asian patients. DBS appears to confer meaningful clinical benefit in selected cases, highlighting the importance of early genetic diagnosis in guiding treatment.

Keywords: DYT‐30; DYT‐VPS16; deep brain stimulation; dystonia.

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References

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