New Clinical Features and a Novel DCDC2 Variant in Neonatal Sclerosing Cholangitis: A Case Report of Two Patients

BackgroundThe DCDC2 gene encodes a protein containing two doublecortin domains, which is localized to cilia and affects ciliary structure. It plays a regulatory role in microtubule protein binding and polymerization. DCDC2 variants are associated with neonatal sclerosing cholangiopathy (NSC), nephronophthisis 19 (NPHP19), and autosomal recessive deafness 66 (DFNB66). The clinical manifestations of DCDC2-related NSC are nonspecific and diverse, including jaundice, acholic stools, hepatomegaly, and splenomegaly, which may progress to end-stage liver disease in childhood. Novel clinical manifestations remain to be discovered.Case presentationIn this study, we present two jaundice-free patients with DCDC2-associated NSC from a consanguineous Chinese family. Patient 1 presented with a sudden onset of upper gastrointestinal bleeding accompanied by hepatosplenomegaly, elevated hepatic transaminases, and elevated gamma-glutamyl transferase (GGT). Patient 2 also lacked jaundice and presented with language developmental delay, autism spectrum disorder, and transient elevation of hepatic enzymes due to EVU virus infection. Additionally, we identified a novel homozygous deletion in exons 3 to 7 of the DCDC2 gene.ConclusionsThe clinical manifestations of DCDC2-associated NSC exhibits significant heterogeneity. Our findings demonstrate that DCDC2-associated NSC may manifest in the absence of jaundice, presenting primarily with upper gastrointestinal hemorrhage, while also being associated with neurodevelopmental features including language delay and autism spectrum disorder. The identification of novel variants in this study extends the variant spectrum of the DCDC2 gene. Our literature analysis suggests that there may be no definitive genotype-phenotype correlation between specific DCDC2 variants and their clinical manifestations, though further research is needed to confirm this observation.