20.500.12556/DiRROS-27846 VIPAS39 related arthrogryposis-renal dysfunction-cholestasis syndrome case report and systematic review 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. ARC syndrome ARCS2 Arthrogryposis–renal dysfunction–cholestasis syndrome VIPAR VIPAS39 sindrom ARC artrogripoza–ledvična disfunkcija–holestazni sindrom true false true Angleški jezik Slovenski jezik Neznano 2026-02-26 11:30:06 2026-02-26 11:30:06 2026-02-27 03:58:36 0000-00-00 00:00:00 2024 0 0 Nasl. z nasl. zaslona; Opis vira z dne 7. 3. 2025; str. 1-12 no. 1, [article no.] 496 Vol. 19 Dec, 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.4-053.2 1750-1172 10.1186/s13023-024-03486-2 228354819 RAZ_Kafol_Jan_2024.pdf RAZ_Kafol_Jan_2024.pdf 1 ACD8FE1C8E05B88BF6D2D82F29277229 3dbec6fcf92731fc25bfc8d1a1e589a204d8b928642c576faf10c755f5df0e46 5d2fd5c7-12fe-11f1-9cb0-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=40975 https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03486-2 1 2155bee6-12fe-11f1-9cb0-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=40974 Univerzitetni klinični center Ljubljana 0 0 0