Arthrogryposis, renal dysfunction, and cholestasis 2

Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VIPAS39 gene that disrupts vesicle‑trafficking pathways required for apical–basolateral polarity in epithelial tissues. Affected individuals present with congenital joint contractures, renal tubular dysfunction, and neonatal cholestasis, often accompanied by ichthyosis, severe failure to thrive, central nervous system anomalies, and variable platelet abnormalities. The phenotype reflects impaired function of the VIPAR–VPS33B complex in polarized liver and kidney cells, leading to widespread epithelial and secretory dysfunction.