Arthrogryposis–renal dysfunction–cholestasis (ARC) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in vacuolar protein sorting 33 homologue B (VPS33B) and VPS33B interacting protein, apical–basolateral polarity regulator (VIPAR). Cardinal features of ARC include congenital joint contractures, renal tubular dysfunction, cholestasis, severe failure to thrive, ichthyosis, and a defect in platelet alpha-granule biogenesis. Most patients with ARC do not survive past the first year of life. We report two patients presenting with a mild ARC phenotype, now 5.5 and 3.5 years old. Both patients were compound heterozygotes with the novel VPS33B donor splice-site mutation c.1225+5G>C in common. Immunoblotting and complementary DNA analysis suggest expression of a shorter VPS33B transcript, and cell-based assays show that c.1225+5G>C VPS33B mutant retains some ability to interact with VIPAR (and thus partial wild-type function). This study provides the first evidence of genotype–phenotype correlation in ARC and suggests that VPS33B c.1225+5G>C mutation predicts a mild ARC phenotype. We have established an interactive online database for ARC (https://grenada.lumc.nl/LOVD2/ARC) comprising all known variants in VPS33B and VIPAR. Also included in the database are 15 novel pathogenic variants in VPS33B and five in VIPAR. Hum Mutat 33:1656–1664, 2012. © 2012 Wiley Periodicals, Inc.

Congenital portosystemic shunts (CPSS) are rare vascular malformations that create an abnormal connection between portal and systemic veins resulting in complete or partial diversion of the portal flow away from the liver to the systemic venous system. Different anatomic types exist and several classifications have been proposed. They can be associated with other malformations especially cardiac and heterotaxia. The main complications include hepatic encephalopathy, liver tumors, portopulmonary hypertension, and pulmonary arteriovenous shunts. Diagnosis relies on imaging, and prenatal diagnosis is possible. Spontaneous closure of the CPSS is possible in some anatomic forms during the first year of life. When the CPSS remains patent, radiologic or surgical closure of the CPSS may prevent, resolve, or stabilize complications. Interventional radiology plays a key role for both the preoperative evaluation with occlusion test to assess the exact anatomy and to measure portal pressure after occlusion of the CPSS. Endovascular closure is the first option for treatment when possible.

No abstract