Portal hypertension in doublecortin domain-containing protein 2 (DCDC2) related neonatal sclerosing cholangitis.

Abstract

Mutations in doublecortin domain-containing protein 2 (DCDC2) lead to neonatal sclerosing cholangitis (NSC), and portal hypertension (PHTN). The objective of the study was to systematically evaluate PHTN, variceal bleeding, and outcomes of patients with DCDC2-related NSC. The study included children with homozygous or compound heterozygous variants in DCDC2. All 14 children with DCDC2-related NSC had PHTN. Eight (57.1%) developed variceal bleed at a median age of 3 years (range: 1.9-5 years). Eleven (78.6%) children with high-risk varices underwent endotherapy. Varices were completely eradicated in three, downstaged to low-risk in five, and there was no response with endotherapy in three. All three children with failure to eradicate/downstage varices had rebleed, and required listing for liver transplantation (LT). The study shows that children with variants in DCDC2 have a high incidence of variceal bleed at a very young age. Variceal eradication may often be difficult and rebleed rates are high; often necessitating LT.