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

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. What is Known Mutations in doublecortin domain‐containing protein (DCDC2) lead to infantile onset cholangiopathy referred to as neonatal sclerosing cholangitis, characterized by cholestasis, pale stools, and high gamma‐glutamyl transpeptidase. Extrahepatic manifestations like nephronophthisis, renal cysts, neurological manifestations, vascular malformations, and sensorineural hearing loss have been described in previous case series. What is New Children with DCDC2 variants have rapidly progressive portal hypertension, and a high incidence of variceal bleed (57.1%) in the first 5 years of life. Variceal eradication is often difficult (eradicated in only 27.3%) and rebleed rates are high. Response to endotherapy is the only predictor of long‐term native liver survival with only 12.5% of responders listed for liver transplantation.