Pediatric Caroli Disease Clinical Presentation

Updated: Oct 20, 2017
  • Author: Mutaz I Sultan, MD, MBChB; Chief Editor: Carmen Cuffari, MD  more...
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The mode of presentation depends on the age of onset and the predominance of renal or hepatic involvement. Children with Caroli syndrome usually have an earlier onset of symptoms and a more progressive disease, given of the effects of both cholangitis and portal hypertension.

Patients with Caroli disease or Caroli syndrome may have a history of intermittent abdominal pain, which reflects episodes of bile stasis or the passage of bile stones. Patients may report pruritus secondary to cholestasis. Patients with cholangitis may report fever and pain in the right upper quadrant.

In Caroli syndrome, portal hypertension may result in hematemesis or melena secondary to bleeding varices. Patients may also develop ascites in association with portal hypertension. Most  (64%) patients who have portal hypertension have autosomal recessive polycystic kidney disease (ARPKD). [3]

Because Caroli syndrome is associated with ARPKD and is inherited in an autosomal recessive manner, the patient may have a family history of kidney or liver disease.



The following may be observed:

  • Hepatomegaly may be present.

  • Splenomegaly may be present if portal hypertension occurs.

  • Tenderness of the right upper quadrant is occasionally present.

  • Abdominal mass or masses occur if large polycystic kidneys are present.

  • Jaundice is rarely present.



A genetic cause is likely, given the association with ARPKD. Mutations in PKHD1 on chromosome 6p21, which is the gene linked to ARPKD, have been identified in patients with Caroli syndrome.

PKHD1 encodes the protein fibrocystin, which is expressed in cortical and medullary ducts in the kidney as well as biliary and pancreatic ducts in a pattern consistent with the histologic patterns seen in ARPKD.

Fibrocystin is one of a larger family of proteins that are present in the primary cilium.

Recent research supports a mechanistic link between ciliary dysfunction and polycystic kidney disease, although this remains controversial. Ciliopathies involving PCK cholangiocytes (cholangiociliopathies) in a rat model appear to be associated with decreased intracellular calcium levels and increased cAMP concentrations, causing cholangiocyte hyperproliferation, abnormal cell matrix interactions, and altered fluid secretion, which ultimately result in bile duct dilatation. [4]

The number of cases of Caroli syndrome caused by PKHD1 mutations is not known.

Caroli syndrome is inherited in an autosomal recessive manner.