VPS13D-Related Disorders: Description of New Variant and Phenotypic Spectrum Based on Age of Onset

Renata Silva de Mendonça; Ana Beatriz Arruda Santana; Andreia Braga Mota Azzoni; Ana Luiza Viegas de Almeida; Matheus Augusto Araujo Castro; Leandro Tavares Lucato; Fernando Kok; Claudio M de Gusmao

doi:10.1007/s12311-025-01938-4

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VPS13D-Related Disorders: Description of New Variant and Phenotypic Spectrum Based on Age of Onset

Journal article

Peer reviewed

VPS13D-Related Disorders: Description of New Variant and Phenotypic Spectrum Based on Age of Onset

Renata Silva de Mendonça, Ana Beatriz Arruda Santana, Andreia Braga Mota Azzoni, Ana Luiza Viegas de Almeida, Matheus Augusto Araujo Castro, Leandro Tavares Lucato, Fernando Kok and Claudio M de Gusmao

Cerebellum (London, England), Vol.24(6), p.183

11/25/2025

DOI: 10.1007/s12311-025-01938-4

PMID: 41288814

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Abstract

The VPS13 family plays a crucial role in mitochondrial stabilization. Biallelic pathogenic variants in VPS13D are classically associated with autosomal recessive ataxia 4 (OMIM #607317), but phenotypic expression is increasingly recognized in diverse presentations such as early-onset movement disorders. We report on two siblings with childhood onset chorea and ataxia. Neuroimaging disclosed bilateral striatal hyperintensities. Whole-exome sequencing identified compound heterozygous likely pathogenic, novel variants in VPS13D: c.2504G > A (p.Trp835*) and c.9107T > C (p.Val3036Ala). To date, 45 cases of VPS13D-related movement disorders have been reported in the literature. Here, we summarize the main clinical findings and compare key features observed in pediatric and adult presentations. Our results indicate that pediatric cases display a distinct phenotype, with some manifestations, such as epilepsy, occurring exclusively in childhood. This study highlights the heterogeneity of VPS13D-related clinical phenotypes. Pediatric presentations appear to follow a more disabling course, with distinct characteristics according to age of onset. Recognition of these features supports the inclusion of VPS13D variants in the differential diagnosis of early-onset chorea, particularly when accompanied by neuroimaging abnormalities and/or associated epilepsy.

Adolescent

Adult

Age of Onset

Child

Chorea - diagnostic imaging

Chorea - genetics

Female

Humans

Male

Mutation

Phenotype

Proteins

Vesicular Transport Proteins - genetics

Details

Title: Subtitle: VPS13D-Related Disorders: Description of New Variant and Phenotypic Spectrum Based on Age of Onset
Creators: Renata Silva de Mendonça - Hospital Amaral Carvalho
Ana Beatriz Arruda Santana - Child Neurology Division, Department of Neurology, Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil
Andreia Braga Mota Azzoni - Child Neurology Division, Department of Neurology, Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil
Ana Luiza Viegas de Almeida - Child Neurology Division, Department of Neurology, Hospital das Clínicas da Faculdade de Medicina, Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil
Matheus Augusto Araujo Castro - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Leandro Tavares Lucato - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Fernando Kok - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Claudio M de Gusmao - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Resource Type: Journal article
Publication Details: Cerebellum (London, England), Vol.24(6), p.183
DOI: 10.1007/s12311-025-01938-4
PMID: 41288814
NLM abbreviation: Cerebellum
ISSN: 1473-4222
eISSN: 1473-4230
Language: English
Date published: 11/25/2025
Academic Unit: Stead Family Department of Pediatrics
Record Identifier: 9985224413702771

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