Adult Congenital Hepatic Fibrosis and Autosomal Dominant Polycystic Kidney Disease with PAX2 and PKD1 Variants: A Case Report

Purpose Congenital hepatic fibrosis (CHF) is a rare ductal plate malformation typically associated with autosomal recessive polycystic kidney disease. Its co-occurrence with autosomal dominant polycystic kidney disease (ADPKD) in adults is exceptionally rare and poses diagnostic challenges. This study reports a case of a 39-year-old female diagnosed with CHF and ADPKD and investigate its genetic underpinnings. Methods The patient underwent a comprehensive diagnostic evaluation, including laboratory testing, abdominal imaging (computed tomography/ultrasonography), transient elastography (FibroScan), and histopathological analysis of a liver biopsy. Genetic analysis was performed using targeted next-generation sequencing (NGS) to identify potential mutations and pedigree analysis was conducted. Results The 39-year-old patient presented with thrombocytopenia and hepatosplenomegaly. Imaging revealed multiple renal cysts and intrahepatic bile duct dilatation with evident signs of portal hypertension, including splenorenal shunts and varices, despite preserved liver synthetic function. Liver biopsy confirmed CHF through characteristic histology. Targeted NGS identified a heterozygous PKD1 mutation (c.2534T > C, p.Leu845Ser) and a maternally inherited PAX2 mutation (c.95C > G, p.Pro32Arg). Notably, the patient lacked ocular anomalies typical of PAX2 -related syndromes. She is currently stable under conservative management. Conclusions This case suggests that the PAX2 variant may act as a genetic modifier, influencing the phenotypic expression of PKD1 -mediated disease to include hepatic fibrosis. Our findings underscore the phenotypic variability of hepatorenal fibrocystic diseases and highlight the utility of genetic profiling in diagnosing atypical presentations in adult patients.