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Case Reports
. 2024 Dec 30;19(1):496.
doi: 10.1186/s13023-024-03486-2.

VIPAS39 related arthrogryposis-renal dysfunction-cholestasis syndrome-case report and systematic review

Jan Kafol  1 , Barbara Gnidovec Strazisar  2   3 , Ana Drole Torkar  1   4 , Matjaz Homan  1   5 , Sara Bertok  1   4 , Matej Mlinaric  1   4 , Jaka Sikonja  1   4 , Jernej Kovač  1   6 , Mirjana Perkovic Benedik  1   7 , Tanja Kersnik Levart  1   8 , Mojca Zerjav Tansek  1   4 , Marina Praprotnik  1   9 , Tadej Battelino  1   4 , Maruša Debeljak  1   6 , Urh Groselj  10   11
Affiliations
Case Reports

VIPAS39 related arthrogryposis-renal dysfunction-cholestasis syndrome-case report and systematic review

Jan Kafol et al. Orphanet J Rare Dis. .

Abstract

Background: Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, a rare autosomal recessive disorder, exhibits genetic heterogeneity with the VIPAS39 gene pathological variants being a distinct contributor.

Results: We present two related patients from Kosovo, describing the clinical, genetic, and therapeutic aspects of the syndrome. The identified novel VIPAS39 pathological variants (c.762G > A; c.1064_1082delinsAGTG) emphasize the complex phenotypic expression of ARC syndrome. A systematic literature review identified 8 VIPAS39-related ARC cases with notable variability in clinical features. Prognostically, patients fell into severe and milder groups, with some reaching adolescence. Our report aligns with others noting milder ARC courses and emphasizes the value of genetic testing, especially in atypical presentations. Challenges included incomplete literature data, early mortality affecting diagnostic workup, and limited VIPAS39-related ARC cases. Comparisons with the more prevalent VPS33B pathological variants revealed no distinct clinical differences.

Conclusion: Our study expands understanding of ARC syndrome, highlighting its genetic diversity and clinical variability. Milder presentations underscore diagnostic challenges and the potential prevalence of undiagnosed cases. Increased awareness and comprehensive genetic testing are crucial for early and accurate diagnosis.

Keywords: ARC syndrome; ARCS2; Arthrogryposis–renal dysfunction–cholestasis syndrome; VIPAR; VIPAS39.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Ethical approval was not required for this study as it is a case report, which does not fall under the scope of research requiring ethics committee approval. Consent for publication: Consent for publication was obtained from the parents of the individuals featured in the manuscript using our institutional consent form. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram for systematic literature review
Fig. 2
Fig. 2
Patient 1 A and Patient 2 B, both displayed dysmorphic features (flat occiput, triangular-shaped face, larger protruding ears, a lower hairline, mild hypertelorism)
Fig. 3
Fig. 3
Common clinical features of reported ARCS2 cases
See this image and copyright information in PMC

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References

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