Objective: To highlight clinical manifestations of VPS13A disease

Background: VPS13A disease causes motor and neuropsychiatric symptoms including dystonia, chorea, tics, and cognitive decline, but can be underrecognized due to its rarity and gradual onset

Method: A 34-year-old male with a past medical history of congenital hydrocephalus without developmental delay presented with a first-time seizure. Although he graduated from college and was previously independent, he started to decline cognitively after his first seizure. Over the next 2 years, he developed worsening balance leading to falls and eventual wheelchair dependence. By age 36, he developed orofacial dystonic movements and tics like self-slapping, spitting, and involuntary vocalizations. By age 41, he developed dysphagia with associated feeding dystonia as well as dysarthric speech. Exam was significant for length-dependent vibratory deficit; reduced reflexes; frequent vocal and motor tics consisting of slapping his face; chorea of the face, jaw, trunk, and upper extremities; dystonic jaw movements and dystonic posturing of the hands. Cranial nerves and strength were normal. There was no family history, and consanguinity was denied.

Results: MRI Brain revealed his known congenital Dandy-Walker variant and ventriculomegaly. Nerve Conduction Study/Electromyography revealed sensorimotor neuropathy. Peripheral smear revealed acanthocytes. Genetic testing identified a homozygous variant in VPS13A (p.(Arg267Ter)(CGA>TGA):c.799 C>T in exon 11). The patient’s mother is heterozygous for the p.(R267*) variant in the VPS13A gene, father’s genetic status is unknown. His seizures are well controlled with levetiracetam and topiramate. Treatment with risperidone resulted in noticeable improvement in his chorea and tics.

Conclusion: This case highlights the clinical complexity and phenotypic heterogeneity of VPS13A-related neurodegenerative diseases. Although in retrospect the clinical presentation is consistent with VPS13A, there was a 10-year delay in diagnosis from the time of initial symptom onset. Due to its insidious, gradual onset, rarity, and phenotypic variability, VPS13A disease can be difficult to recognize and diagnose. In patients with seizures, movement disorders, and cognitive/behavioral changes, VPS13A disease should be considered. Early recognition and genetic testing are crucial for the diagnosis, enabling timely management, improving quality of life.

References: 1. Peikert K, Dobson-Stone C, Rampoldi L, Miltenberger-Miltenyi G, Neiman A, De Camilli P, Hermann A, Walker RH, Monaco AP, Danek A. VPS13A Disease. 2002 Jun 14 [updated 2023 Mar 30]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301561.
2. Peikert K, Danek A, Hermann A. Current state of knowledge in Chorea-Acanthocytosis as core Neuroacanthocytosis syndrome. Eur J Med Genet. 2018 Nov;61(11):699-705. doi: 10.1016/j.ejmg.2017.12.007. Epub 2017 Dec 16. PMID: 29253590.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/choreadystonia-and-ticslessons-learned-from-the-clinical-pattern-associated-with-vps13a-disease/