PKD1 – Caroli Disease

Caroli disease is a rare congenital disorder characterized by cystic dilatation of the intrahepatic bile ducts and increased risk of cholangiocellular carcinoma (PMID:10517920). Familial clustering in association with autosomal dominant polycystic kidney disease (ADPKD) has been observed, notably a single patient heterozygous for a large deletion encompassing exons 1–44 of PKD1 who developed ADPKD and Caroli disease with hepatosplenomegaly and recurrent cholangitis (PMID:21470545). No molecularly defined PKD1 variants have been reported in isolated Caroli disease, and there is no segregation or experimental data linking PKD1 to biliary duct pathology, supporting a Limited clinical validity rating.

Genetic evidence is limited to one proband with a PKD1 deletion in the context of ADPKD and Caroli disease; no additional unrelated cases or segregation data are available. Functional studies of PKD1 have focused on renal cystogenesis in ADPKD and have not addressed biliary epithelium or ductal dilatation. Further case ascertainment and targeted functional models are needed to clarify any direct role of PKD1 in Caroli disease.

Key take-home: While PKD1 mutations can co-occur with Caroli disease in ADPKD patients, evidence remains Limited and does not support routine PKD1 testing for isolated Caroli disease.

References

• Gut • 1999 • Clonal chromosomal abnormalities in congenital bile duct dilatation (Caroli's disease). PMID:10517920
• Canadian Urological Association journal • 2011 • Nephrectomy in patients with Caroli's and ADPKD may be associated with increased morbidity. PMID:21470545

Evidence Based Scoring (AI generated)