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<p>The <i>VPS13</i> family plays a crucial role in mitochondrial stabilization. Biallelic pathogenic variants in <i>VPS13D</i> 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.&#xa0;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 <i>VPS13D</i>: c.2504G &gt; A (p.Trp835*) and c.9107T &gt; C (p.Val3036Ala). To date, 45 cases of <i>VPS13D</i>-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.&#xa0;This study highlights the heterogeneity of <i>VPS13D</i>-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 <i>VPS13D</i> variants in the differential diagnosis of early-onset chorea, particularly when accompanied by neuroimaging abnormalities and/or associated epilepsy.</p>

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

  • 期刊论文

  • 发表日期：

    2025年11月25日

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  • 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

摘要

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.