ORIGINAL PAPER
A novel form of intrahepatic cholestasis: neonatal sclerosing cholangitis due to DCDC2 pathogenic variants. Clinical recognition and diagnostic approach
1
Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children’s Memorial Health Institute, Warsaw, Poland
2
Maria Skłodowska Curie Medical Academy, Warsaw, Poland
3
Department of Nephrology, Kidney Transplantation and Hypertension, Children’s Memorial Health Institute, Warsaw, Poland
4
Department of Medical Genetics, Children’s Memorial Health Institute, Warsaw, Poland
5
Department of Pathology, Children’s Memorial Health Institute, Warsaw, Poland
Submission date: 2025-06-30
Acceptance date: 2025-07-28
Publication date: 2025-09-24
Pediatr Pol 2025;61(3):236-242
KEYWORDS
cholestasisneonatal sclerosing cholangitispathogenic variantsDCDC2liver fibrosisliver transplantation
TOPICS
ABSTRACT
Introduction:
Neonatal sclerosing cholangitis (NSC) caused by pathogenic variants in the DCDC2 gene is a rare and severe form of cholangiopathy, classified as a ciliopathy. The aim of this study was to analyze the clinical features of seven patients diagnosed with NSC treated in our center and to compare them with previously reported cases in the literature. Particular attention was paid to the similarities and differences between DCDC2-related NSC and biliary atresia, as they can present with overlapping features in early infancy. So far, no description of this disease has been found in the Polish literature.
Material and methods:
We reviewed clinical, biochemical, and imaging data from seven patients with genetically confirmed NSC caused by biallelic pathogenic variants in the DCDC2 gene. These data were compared with descriptions of patients diagnosed with NSC published in the literature, taking into account the course of the disease, diagnostic methods, and treatment strategies.
Results:
Most patients with NSC present in early infancy with cholestatic jaundice with high g-glutamyl transpeptidase activity, which usually resolves at the age of 12 months. Subsequently, symptoms such as hepatomegaly and splenomegaly and features of portal hypertension with hypersplenism and gastrointestinal varices begin to dominate. Patients require systematic endoscopic surveillance and repeated sessions of ligation of esophageal varices. So far, one of our own patients and more than half of the patients described in the literature have required liver transplantation.
Conclusions:
NSC caused by a biallelic pathogenic variants in the DCDC2 gene is a rare ciliopathy that can mimic the course of biliary atresia in the neonatal period. In later life, liver fibrosis becomes the predominant manifestation, often leading to the development of portal hypertension. With the development and availability of molecular tests, it should be expected that the group of DCDC2-related NSC confirmed by genetic testing will systematically grow.
Neonatal sclerosing cholangitis (NSC) caused by pathogenic variants in the DCDC2 gene is a rare and severe form of cholangiopathy, classified as a ciliopathy. The aim of this study was to analyze the clinical features of seven patients diagnosed with NSC treated in our center and to compare them with previously reported cases in the literature. Particular attention was paid to the similarities and differences between DCDC2-related NSC and biliary atresia, as they can present with overlapping features in early infancy. So far, no description of this disease has been found in the Polish literature.
Material and methods:
We reviewed clinical, biochemical, and imaging data from seven patients with genetically confirmed NSC caused by biallelic pathogenic variants in the DCDC2 gene. These data were compared with descriptions of patients diagnosed with NSC published in the literature, taking into account the course of the disease, diagnostic methods, and treatment strategies.
Results:
Most patients with NSC present in early infancy with cholestatic jaundice with high g-glutamyl transpeptidase activity, which usually resolves at the age of 12 months. Subsequently, symptoms such as hepatomegaly and splenomegaly and features of portal hypertension with hypersplenism and gastrointestinal varices begin to dominate. Patients require systematic endoscopic surveillance and repeated sessions of ligation of esophageal varices. So far, one of our own patients and more than half of the patients described in the literature have required liver transplantation.
Conclusions:
NSC caused by a biallelic pathogenic variants in the DCDC2 gene is a rare ciliopathy that can mimic the course of biliary atresia in the neonatal period. In later life, liver fibrosis becomes the predominant manifestation, often leading to the development of portal hypertension. With the development and availability of molecular tests, it should be expected that the group of DCDC2-related NSC confirmed by genetic testing will systematically grow.
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