Arthrogryposis–renal dysfunction–cholestasis (ARC) syndrome: from molecular genetics to clinical features

ABSTRACT: Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare but fatal autosomal recessive multisystem disorder caused by mutations in the VPS33B or VIPAR gene. The classical presentation of ARC includes congenital joint contractures, renal tubular dysfunction, and cholestasis. Additional features include ichthyosis, central nervous system malformation, platelet anomalies, and severe failure to thrive. Diagnosis of ARC syndrome relies on clinical features, organ biopsy, and mutational analysis. However, no specific treatment currently exists for this syndrome. CONCLUSION: This is an overview of the latest knowledge regarding the genetic features and clinical manifestations of ARC syndrome. Greater awareness and understanding of this syndrome should allow more timely intervention with potential for improving long-term outcome.