Neuropathy-predominant and hyperkinetic-dystonic presentations in two siblings with a homozygous VPS13A variant: long-term follow-up and family-based clinical analysis

Abstract

Background

VPS13A disease, historically known as chorea-acanthocytosis, is a rare autosomal recessive neurodegenerative disorder characterized by variable combinations of chorea, dystonia, orolingual involvement, cognitive or psychiatric changes, acanthocytosis, and peripheral neuromuscular abnormalities. Although phenotypic heterogeneity is well recognized, neuropathy-predominant onset may delay diagnostic recognition, particularly before typical hyperkinetic or orolingual features become apparent.

Case presentation

We describe two affected siblings from a consanguineous family who carried the same homozygous VPS13A missense variant and were followed for more than 10 years. The younger sister developed symptoms at 27 years of age with severe choreiform movements and prominent lingual/orofacial dystonia, which was partially relieved by placing a towel in the mouth and was considered consistent with a possible sensory trick. The older brother developed symptoms at 32 years of age with mild peripheral neuropathic symptoms and later developed facial/orofacial involuntary movements that progressed to more prominent choreiform and orofacial features in the later disease stage. Cognitive decline, acanthocytosis, and mild axonal peripheral neuropathy were documented in both siblings. Brain MRI in the younger sister showed findings suggestive of mild caudate atrophy. Genetic testing identified a homozygous VPS13A c.2964G > C [p.(Lys988Asn)] variant in both affected siblings, whereas family validation showed heterozygous carrier status in the parents. The variant was absent from the gnomAD East Asian population database and remained classified as a variant of uncertain significance by the reporting laboratories.

Conclusions

This family illustrates that a VPS13A disease-like phenotype associated with a plausible candidate VPS13A variant may follow markedly different clinical trajectories even within the same sibship, including neuropathy-predominant onset and a hyperkinetic-dystonic presentation. The findings emphasize the need to reconsider VPS13A disease when peripheral neuropathy is accompanied or followed by progressive choreiform movements, orolingual dystonia, cognitive decline, acanthocytosis, or caudate atrophy. Although functional validation was unavailable, the characteristic phenotype, rarity of the variant, and segregation pattern support its clinical relevance as a plausible candidate variant associated with the phenotype, rather than as definitive proof of pathogenicity.

Background

VPS13A disease, historically known as chorea-acanthocytosis and belonging to the neuroacanthocytosis spectrum, is a rare autosomal recessive neurodegenerative disorder caused by biallelic pathogenic variants in VPS13A [1–3]. It is classically associated with chorea, dystonia, prominent orolingual involvement, cognitive or psychiatric symptoms, seizures in some patients, acanthocytosis, and peripheral neuromuscular abnormalities [3–10]. Although the combination of hyperkinetic movements, orolingual dystonia, caudate atrophy, and acanthocytosis is highly suggestive, diagnosis may be delayed because early manifestations are often incomplete or atypical [3, 5, 6, 8, 9].

Clinical heterogeneity is increasingly recognized in VPS13A disease [3, 5, 6]. Patients may differ substantially in age at onset, initial symptoms, severity of hyperkinetic movements, degree of cognitive or psychiatric involvement, and extent of peripheral neuromuscular abnormalities [3–7, 10]. Reports from different populations, including Chinese families, have further expanded the recognized clinical and genetic spectrum [11, 12]. Peripheral neuropathy or neuromuscular symptoms may precede or overshadow the movement disorder phenotype, shifting the initial diagnostic workup toward peripheral nerve disease rather than hereditary neurodegenerative movement disorders [3–5, 7]. This may be especially challenging when acanthocytosis is mild, neuroimaging findings are subtle, or genetic results remain formally classified as variants of uncertain significance.

Here, we describe two affected siblings from a consanguineous family who carried the same homozygous VPS13A missense variant but followed markedly different long-term clinical trajectories. The younger sister presented with severe choreiform movements and prominent lingual/orofacial dystonia, whereas the older brother initially showed a neuropathy-predominant presentation and developed hyperkinetic features later, which became clinically prominent in the later disease stage. By integrating long-term clinical follow-up with hematologic, electrophysiological, neuroimaging, and family-based genetic evidence, this report highlights the diagnostic importance of recognizing divergent clinical entry points into the clinical spectrum of VPS13A disease.

Case presentation

Family background

The affected siblings were born to consanguineous parents. Two siblings were clinically affected, whereas the parents were reported by family members to be clinically unaffected; however, direct neurological examination of the parents was not available. The younger sister was the proband and had a more severe hyperkinetic-dystonic phenotype. The older brother developed neurological symptoms later and initially showed a milder neuropathy-predominant presentation. The family history and subsequent segregation results were compatible with an autosomal recessive pattern of inheritance (Fig. 1).

Fig. 1.

Pedigree and genetic findings in the consanguineous family carrying a homozygous VPS13A missense variant. A Pedigree of the family showing two affected siblings born to consanguineous parents. Squares indicate males and circles indicate females. Filled symbols indicate affected individuals. The arrow denotes the proband. Double horizontal lines indicate consanguinity. B Sanger sequencing chromatogram from the younger sister, the proband (IV-1), showing the homozygous VPS13A c.2964G > C variant. C Sanger sequencing chromatogram from the affected older brother (IV-2), confirming the same homozygous VPS13A c.2964G > C variant. D Sanger sequencing chromatogram from the father (III-1), demonstrating heterozygous carrier status at the same locus. E Sanger sequencing chromatogram from the mother (III-2), demonstrating heterozygous carrier status at the same locus

Clinical information was collected retrospectively from long-term follow-up records, neurological examinations, peripheral blood smear reports, electrophysiological studies, available brain MRI, and clinical genetic testing reports. Because the two siblings were evaluated and followed over an extended period, not all ancillary investigations were available at identical time points. Nevertheless, the available data allowed direct comparison of their clinical trajectories and supportive diagnostic findings.

Younger sister: hyperkinetic-dystonic presentation

The younger sister developed neurological symptoms at 27 years of age. From the early stage of the disease, her presentation was dominated by severe choreiform movements and prominent lingual/orofacial dystonia. Tongue involvement was particularly disabling in daily life and was partly relieved by placing a towel in the mouth, a feature consistent with a possible sensory trick and supportive of a dystonic component rather than purely choreiform tongue movements.

During follow-up, the movement disorder progressed, and cognitive decline became clinically evident around 2018. Mild distal numbness developed approximately 5 years after symptom onset and remained relatively mild. Peripheral blood smear examination documented acanthocytosis of 8%. Although the original smear image was unavailable because of archival loss, the result had been clearly recorded in the clinical records. Electrophysiological studies performed in 2016, approximately 10 years after symptom onset, showed reduced sensory nerve action potential amplitudes in the left median nerve (3.8 µV), ulnar nerve (4.2 µV), and superficial peroneal nerve (2.1 µV), with an absent sural sensory response. Sensory conduction velocities were in the low-normal range. Motor conduction studies of the median, ulnar, peroneal, and tibial nerves showed preserved or low-normal compound muscle action potential amplitudes, normal conduction velocities, normal distal latencies, and normal F-wave latencies. Needle EMG did not show definite neurogenic changes, except for rare fibrillation potentials in the tibialis anterior muscle. These findings supported mild sensory-predominant axonal peripheral neuropathy without convincing electrophysiological evidence of definite motor axonal neuropathy.

Brain MRI of the younger sister was performed in 2016, approximately 10 years after symptom onset. Although the original clinical report did not highlight major abnormalities, retrospective review of the available axial T2-weighted and coronal FLAIR images showed findings suggestive of mild caudate atrophy, reflected by mild narrowing of the caudate head contour and relative enlargement of the frontal horns (Fig. 2A, B). No obvious cortical atrophy, cerebellar atrophy, major white matter lesions, or other structural abnormalities were evident on the available images. Quantitative volumetric analysis was not possible because original DICOM data were unavailable. Taken together, the combination of severe choreiform movements, lingual/orofacial dystonia, acanthocytosis, mild imaging findings suggestive of caudate atrophy, cognitive decline, and peripheral neuropathy was highly consistent with the clinical spectrum of VPS13A disease.

Fig. 2.

Brain MRI of the younger sister and peripheral blood smear of the older brother. A, B Brain MRI of the younger sister obtained in 2016, approximately 10 years after symptom onset, showing findings suggestive of mild caudate atrophy on axial T2-weighted and coronal FLAIR images. Quantitative volumetric analysis was unavailable. C Peripheral blood smear from the older brother showing acanthocytosis (5%). Acanthocytosis was also documented in the younger sister (8%), although her smear image was unavailable. Scale bar = 14 μm

Older brother: neuropathy-predominant onset

The older brother developed neurological symptoms at 32 years of age, approximately 5 years after his sister. In contrast to the proband, his earliest complaints were mild peripheral neuropathic symptoms rather than obvious hyperkinetic movements. This initial presentation directed clinical attention toward a peripheral nerve disorder. Over time, however, he gradually developed mild facial/orofacial involuntary movements, which were retrospectively reported approximately 8 years after the neuropathic onset. These movements became more prominent during the 2 years before the 2026 evaluation, with worsening orofacial involvement and the emergence of truncal and limb choreiform movements. Although his hyperkinetic-dystonic manifestations were initially much less severe than those of his sister, they became clinically prominent in the later disease stage.

Cognitive decline was documented in 2026. Peripheral blood smear examination documented acanthocytosis of 5%, and a representative smear image was available (Fig. 2C). Nerve conduction studies performed approximately 1 year after the onset of neuropathic symptoms showed reduced sensory nerve action potential amplitudes in the right median nerve (2.5 µV), ulnar nerve (3.5 µV), and superficial peroneal nerve (1.8 µV), with an absent sural sensory response. Motor studies showed mildly reduced compound muscle action potential amplitudes in the median nerve (3.8 mV), ulnar nerve (4.2 mV), peroneal nerve (2.1 mV), and tibial nerve (3.2 mV). Motor conduction velocities were preserved or in the low-normal range, whereas distal latencies and F-wave latencies were mildly prolonged in the lower-limb motor nerves. Needle EMG showed mild neurogenic changes, predominantly in distal muscles, including rare fibrillation potentials and mildly prolonged motor unit potential durations, suggesting mild chronic motor axonal involvement with partial reinnervation. These findings supported mild axonal sensorimotor peripheral neuropathy. Brain MRI of the older brother had reportedly been performed at an outside hospital approximately 8 years before the 2026 evaluation; however, the images and written report were unavailable for review. Therefore, imaging comparison between the two siblings could not be performed. Taken together, his clinical course suggested a neuropathy-predominant onset followed by later emergence of features clinically compatible with VPS13A disease, including orofacial dystonia, choreiform movements, cognitive decline, and acanthocytosis.

The contrast between the two siblings was clinically striking. The younger sister had an early and severe hyperkinetic-dystonic presentation with prominent lingual involvement, whereas the older brother initially appeared to have mild peripheral neuropathy and only later developed hyperkinetic features that became clinically prominent in the later disease stage. This divergence provided an opportunity to compare two different clinical entry points into the same family-based clinical spectrum of VPS13A disease. The main clinical differences between the two affected siblings are summarized in Table 1.

Table 1.

Clinical comparison and longitudinal features of the two affected siblings

Feature	Younger sister / proband	Older brother
Sex	Female	Male
Family background	Born to consanguineous parents	Born to consanguineous parents
Age at neurological onset	27 years	32 years
Initial presentation	Severe choreiform movements and prominent lingual/orofacial dystonia	Mild peripheral neuropathic symptoms, mainly numbness without weakness
Age at last documented clinical evaluation	Approximately 45–46 years (approximately 2025)	48 years at the 2026 clinical/genetic evaluation
Disease duration at last documented evaluation	Approximately 18–19 years	Approximately 16 years from neuropathic onset
Movement disorder course	Severe hyperkinetic-dystonic manifestations were present from the early disease stage	Peripheral neuropathic symptoms predominated initially. Mild facial/orofacial involuntary movements were retrospectively reported approximately 8 years before the 2026 evaluation; symptoms worsened over the preceding 2 years, with more prominent orofacial movements and truncal/limb choreiform movements becoming severe in 2026
Lingual/orofacial dystonia	Marked lingual/orofacial dystonia	Mild orofacial/oromandibular dystonic or involuntary movements that became more evident later
Possible sensory trick	Partial relief by placing a towel in the mouth	Not reported
Peripheral neuropathic symptoms	Mild distal numbness developed approximately 5 years after onset and remained relatively mild	Present from onset and constituted the initial dominant clinical feature
Timing of electrophysiological study	NCS/EMG performed in 2016, approximately 10 years after neurological onset	NCS/EMG performed approximately 1 year after neuropathic onset
Electrophysiological findings	Mild sensory-predominant axonal peripheral neuropathy; no convincing electrophysiological evidence of definite motor axonal neuropathy	Mild axonal sensorimotor peripheral neuropathy, with mild chronic motor axonal involvement and partial reinnervation in distal muscles
Cognitive decline	Documented around 2018, approximately 12 years after onset	Documented in 2026
Acanthocytosis	8%; original smear image unavailable because of archival loss	5%; representative smear image available
Brain MRI	Available 2016 brain MRI images, reviewed for this report, showed findings suggestive of mild caudate atrophy on axial T2-weighted and coronal FLAIR images; quantitative volumetric analysis was unavailable.	Brain MRI was reportedly performed at an outside hospital approximately 8 years before the 2026 evaluation, but the images/report were unavailable for review.
Genetic testing and family validation	Exome-based sequencing in 2016 identified a homozygous VPS13A c.2964G > C variant; family validation showed that both parents were heterozygous carriers	Earlier targeted family validation/Sanger sequencing confirmed the same homozygous VPS13A c.2964G > C variant; a later 2026 clinical genetic report re-documented the variant and provided updated annotation and ACMG/AMP-based interpretation
Overall clinical interpretation	Severe hyperkinetic-dystonic presentation clinically compatible with the VPS13A disease spectrum	Neuropathy-predominant presentation with later hyperkinetic/orofacial and choreiform features, clinically compatible with the VPS13A disease spectrum

Timelines are based on retrospective clinical review and available clinical/genetic reports; approximate wording is used where exact onset dates could not be reliably determined

ACMG/AMP American College of Medical Genetics and Genomics/Association for Molecular Pathology, EMG electromyography, FLAIR fluid-attenuated inversion recovery, MRI magnetic resonance imaging, NCS nerve conduction studies, VPS13A vacuolar protein sorting 13 homolog A

Genetic findings and family validation

Clinical genetic testing identified the same homozygous VPS13A variant in both affected siblings. In the proband, exome-based sequencing performed in 2016 identified a homozygous VPS13A c.2964G > C variant, reported as p.K988N according to the transcript used by the testing laboratory, and family validation showed that both parents were heterozygous carriers. Targeted family validation confirmed the same homozygous variant in the affected older brother. A later clinical genetic report in the older brother annotated the variant according to the reference transcript NM_033305.3 as VPS13A c.2964G > C [p.(Lys988Asn)], located in exon 28, with the genomic coordinate chr9:77281926 on GRCh38/hg38. The variant was detected in the homozygous state with an allelic ratio of 1.00. Maternal validation again showed heterozygous carrier status.

The variant was reported as absent from the gnomAD East Asian population database and had not been reported in PubMed according to the later clinical report. The earlier report also stated that the variant had not been reported in HGMDpro. Computational predictions were mixed: REVEL was 0.108, which did not support a deleterious missense effect, whereas SpliceAI was 0.800, suggesting a possible splicing effect. No RNA analysis was available to confirm a splicing effect. Thus, although the variant was annotated at the protein level as p.(Lys988Asn), the high SpliceAI score raises the possibility that any potential biological effect, if present, may involve aberrant splicing rather than a simple missense effect alone.

The variant remained classified as a variant of uncertain significance by the reporting laboratories. The ACMG/AMP evidence documented in the later report was PM2_Supporting and PM3_Supporting. These criteria were reported as documented in the clinical report and were treated as supportive evidence only; they were not used to upgrade the variant beyond a variant of uncertain significance in the present manuscript. In the present family, the segregation pattern and highly compatible phenotype were considered clinically supportive; however, because functional validation, such as chorein expression or RNA analysis, was unavailable, the variant was interpreted as a plausible candidate variant associated with the phenotype rather than as a proven pathogenic variant.

Overall, the genetic data were interpreted in the context of the clinical phenotype rather than as standalone proof of pathogenicity. Taken together, the same homozygous VPS13A variant in both affected siblings, heterozygous carrier status in the parents, and concordance with characteristic clinical, hematologic, electrophysiological, and imaging findings supported the clinical relevance of this plausible candidate variant, while definitive pathogenicity could not be established. Detailed genetic and variant interpretation data are summarized in Table 2.

Table 2.

Genetic and variant interpretation data for the VPS13A c.2964G > C [p.(Lys988Asn)] variant

Item	Result
Gene	VPS13A
Reference transcript	NM_033305.3
Exon	Exon 28
Nucleotide change	c.2964G > C
Protein change	p.(Lys988Asn); reported as p.K988N in the earlier 2016 laboratory report
Genomic coordinate	chr9:77281926, GRCh38/hg38
Earlier genomic coordinate	chr9:79896842 in the 2016 report; the genome build was not specified. The later report annotated the same nucleotide/protein change as chr9:77281926 on GRCh38/hg38
Zygosity in the younger sister/proband	Homozygous
Zygosity in the older brother	Homozygous
Parental validation	Both parents were heterozygous carriers in the 2016 family validation; maternal heterozygosity was reconfirmed in the later report
Population frequency	gnomAD East Asian frequency: 0
ClinVar	No exact ClinVar entry for this variant was identified at the time of revision
Literature/database information	Not reported in PubMed according to the later clinical report; not reported in HGMDpro according to the earlier report
REVEL	0.108
SpliceAI	0.800
CNV analysis	No clinically relevant exon-level CNV was detected in the proband; no clinically significant CNV was detected in the older brother’s later report
STR analysis	No clinically significant repeat expansion was detected in the older brother’s later report among the tested STR panel
ACMG/AMP evidence documented by the later report	PM2_Supporting + PM3_Supporting
Laboratory classification	Variant of uncertain significance
Interpretation in this manuscript	Plausible candidate variant associated with the phenotype; definitive pathogenicity could not be established without functional validation

The earlier 2016 report used p.K988N and chr9:79896842 without specifying the genome build, whereas the later report annotated the same nucleotide/protein change as p.(Lys988Asn) and chr9:77281926 on GRCh38/hg38. Computational predictions were considered supportive only and were not used as proof of pathogenicity

Abbreviations: ACMG/AMP American College of Medical Genetics and Genomics/Association for Molecular Pathology, CNV copy-number variant, gnomAD Genome Aggregation Database, STR short tandem repeat, VUS variant of uncertain significance

Discussion

The main finding of this family is not merely intrafamilial phenotypic heterogeneity, which has been previously recognized in VPS13A disease, but the presence of two distinct clinical entry points into the same disease spectrum [3, 5, 6]. The younger sister presented with a severe hyperkinetic-dystonic syndrome dominated by choreiform movements and prominent lingual/orofacial dystonia, whereas the older brother initially showed a neuropathy-predominant presentation and developed hyperkinetic and dystonic features later, which became clinically prominent in the later disease stage. The long-term follow-up of these siblings therefore illustrates how VPS13A disease may be recognized through different clinical pathways even within the same sibship.

The older brother’s early presentation is clinically important because mild axonal peripheral neuropathy may direct the diagnostic workup toward peripheral nerve disease and away from hereditary neurodegenerative movement disorders. In VPS13A disease, peripheral neuromuscular involvement may coexist with, precede, or be overshadowed by hyperkinetic manifestations [3–5, 7]. When neuropathic symptoms are followed by or accompanied by choreiform movements, orofacial dystonia, cognitive decline, acanthocytosis, or striatal atrophy, clinicians should reconsider a broader neurogenetic diagnosis rather than treating the neuropathy as an isolated disorder. This diagnostic perspective may be particularly relevant in patients from consanguineous families or in families with more than one affected sibling.

The differential diagnosis in this family included other neuroacanthocytosis-spectrum disorders, Huntington disease and Huntington disease-like disorders, and hereditary neuropathies associated with movement disorders. McLeod syndrome and other neuroacanthocytosis-spectrum disorders may share chorea, acanthocytosis, and neuropsychiatric manifestations, but the autosomal recessive inheritance pattern, consanguineous background, affected siblings of both sexes, and the shared homozygous VPS13A variant supported a clinical diagnosis compatible with VPS13A disease in the present family. Huntington disease and Huntington disease-like disorders may present with chorea and caudate atrophy, but prominent orolingual dystonia, acanthocytosis, peripheral neuropathy, and recessive segregation were less typical. Hereditary neuropathies with superimposed movement disorders were also considered, particularly in the older brother; however, the later emergence of orofacial dystonia, choreiform movements, cognitive decline, acanthocytosis, and the shared homozygous VPS13A variant favored a unified diagnosis within the clinical spectrum of VPS13A disease.

The younger sister’s orolingual phenotype also provides a useful bedside clue. Orolingual and orofacial involvement is among the most recognizable clinical features of VPS13A disease [3–5, 7]. Abnormal tongue movements may be described nonspecifically as chorea in routine practice, but in this patient, the marked lingual involvement and partial improvement after placing a towel in the mouth supported a dystonic component and resembled a possible sensory trick. Recognizing this feature is clinically relevant because it may help distinguish dystonic orolingual involvement from nonspecific hyperkinetic tongue movements and may prompt targeted evaluation for VPS13A disease and related neuroacanthocytosis-spectrum disorders.

The genetic interpretation of this family requires caution. The identified VPS13A c.2964G > C [p.(Lys988Asn)] missense variant remained classified as a variant of uncertain significance by the reporting laboratories and was interpreted according to ACMG/AMP-based criteria [13]. Nevertheless, several lines of evidence support its clinical relevance: the variant was absent from the gnomAD East Asian population database, both affected siblings carried the variant in the homozygous state, and parental testing showed heterozygous carrier status consistent with autosomal recessive inheritance. The later clinical report documented PM2_Supporting and PM3_Supporting. Computational predictions were mixed, with a low REVEL score but a high SpliceAI score suggesting a possible splicing effect; however, no RNA analysis was available to confirm this predicted effect. Importantly, these findings should not be interpreted as definitive proof of pathogenicity, because computational and segregation evidence must be interpreted in conjunction with validated functional and phenotypic evidence [13–16]. Rather, the clinical phenotype, segregation pattern, acanthocytosis, electrophysiological findings, and imaging findings suggestive of caudate atrophy together support a clinically meaningful association between the phenotype and this plausible candidate VPS13A variant, while functional validation remains unavailable.

This report has several strengths and limitations. The strengths include long-term follow-up, direct comparison of two affected siblings, family-based genetic validation, and multimodal supportive evidence including hematologic, electrophysiological, neuroimaging, and clinical genetic findings. The main limitations are the small family-based design, lack of standardized longitudinal motor and cognitive rating scales, archival loss of the younger sister’s peripheral blood smear image, and absence of erythrocyte chorein expression or other functional assays. Imaging evidence was also limited because quantitative volumetric analysis was not available for the younger sister and the older brother’s outside-hospital MRI could not be retrieved. In addition, raw sequencing data were not available to the authors because genetic testing was performed by third-party clinical laboratories. Despite these limitations, this family emphasizes that VPS13A disease should be considered not only in patients with a classic hyperkinetic, orolingual, and acanthocytosis-associated phenotype, but also in those with neuropathy-predominant onset who later develop progressive orolingual dystonia, choreiform movements, cognitive decline, acanthocytosis, or caudate atrophy.

Conclusions

This family highlights that a VPS13A disease-like phenotype associated with a plausible candidate VPS13A variant may present through different clinical entry points even within the same sibship. Neuropathy-predominant onset should not exclude VPS13A disease, particularly when progressive orolingual dystonia, choreiform movements, cognitive decline, acanthocytosis, or caudate atrophy subsequently emerge. The combination of long-term follow-up, hematologic and electrophysiological findings, neuroimaging features, and family-based genetic validation supports the clinical relevance of the identified homozygous VPS13A variant as a plausible candidate associated with the phenotype, although functional validation remains unavailable and definitive pathogenicity could not be established. Recognition of such divergent clinical trajectories may help clinicians avoid delayed diagnosis in patients with atypical or initially neuropathy-predominant presentations.

Abbreviations

ACMG/AMP

American College of Medical Genetics and Genomics/Association for Molecular Pathology

FLAIR

fluid-attenuated inversion recovery

MRI

magnetic resonance imaging

VUS

variant of uncertain significance

WES

whole-exome sequencing

Authors' contributions

YL conceived the study, collected and interpreted the clinical data, drafted the manuscript, and revised the manuscript critically for important intellectual content. JC contributed to clinical interpretation and manuscript revision. TL contributed to data collection and clinical follow-up. XN contributed to clinical data organization and figure preparation. YX contributed to genetic data interpretation and manuscript revision. All authors read and approved the final manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

The clinical data supporting the findings of this study are available from the corresponding author upon reasonable request, subject to institutional approval and patient privacy restrictions. Genetic testing was performed by third-party clinical laboratories, and the authors had access to clinical genetic reports and report-level variant information. De-identified report-level genetic information relevant to the reported VPS13A variant can be made available from the corresponding author upon reasonable request, subject to institutional approval and patient privacy restrictions. Raw sequencing files, including FASTQ, BAM, and VCF files, were not provided to the authors and are therefore not publicly available.

Declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of Jinhua Municipal Central Hospital. No specific approval number was assigned by the ethics committee. Written informed consent to participate was obtained from the older brother and from an authorized family representative of the younger sister.

Consent for publication

Written informed consent for publication of anonymized clinical, imaging, hematologic, electrophysiological, and genetic information was obtained from the older brother and from an authorized family representative of the younger sister.

Competing interests

The authors declare no competing interests.