Background: Caroli disease is a rare ductal plate malformation. While most polycystic kidney and hepatic disease 1 (PKHD1)-related biliary phenotypes arise from compound-heterozygous variants, the prenatal implications of homozygous variants remain unclear. Reporting the first prenatal diagnosis linked to a homozygous PKHD1 variant, along with the diagnostic workflow, has direct implications for genetic counseling and recurrence prevention strategies. Case: A 25-year-old woman, gravida 2, presented with isolated fetal intrahepatic bile duct dilatation at 22+5 weeks of gestation. Ultrasound showed arborizing, avascular tubular channels; and fetal magnetic resonance imaging (MRI) confirmed diffuse intrahepatic involvement with normal renal anatomy. Karyotype analysis and chromosomal microarray were normal. Trio-exome sequencing identified a homozygous PKHD1 c.2507T>C (p.Val836Ala) variant, and Sanger sequencing confirmed parental heterozygosity. Interval surveillance documented enlargement to 47 × 37 × 24 mm. Following multidisciplinary counseling, the pregnancy was electively terminated, and no autopsy was performed. The early, isolated hepatobiliary presentation contrasts with previously reported compound-heterozygous cases. Conclusions: Combined ultrasound, fetal MRI, and trio-exome sequencing established an etiologic prenatal diagnosis and refined the differential diagnosis from choledochal cyst and cystic biliary atresia. The homozygous c.2507T>C variant likely confers a dosage-dependent, more severe fetal phenotype, thereby expanding the PKHD1-associated spectrum and strengthening genotype–phenotype correlations. These findings provide direct clinical utility and educational value by highlighting key imaging features, outlining a stepwise genomic diagnostic workflow, and emphasizing the utility of preimplantation genetic testing to prevent recurrence.
Wang et al. (Wed,) studied this question.