Recurrent intrahepatic cholestasis of pregnancy in conjuntion with a frameshift deletion in FGFR4

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease in pregnant women. ICP usually becomes apparent in the third trimester of pregnancy. The condition resolves usually after delivery, and clinical signs and symptoms disappear. ICP is caused by a multifactorial etiology with hormonal, environmental and genetic factors contributing to the development of the disease. To date, causal variants in hepatobiliary ATP-binding cassette transporters for phosphatidylcholine (ABCB4) and bile acids (ABCB11) have been identified. Here, we present the case of a 29-year old women with recurrent ICP and severe pruritus in two consecutive pregnancies. Exome sequencing (NGS) revealed a previously not described deletion (c.393_delG) in the Fibroblast growth factor receptor 4 (FGFR4) gene causing a frameshift and a dysfunctional protein. Pathogenic ABCB4 and ABCB11 mutations were not detected. FGFR4 is the hepatic receptor for the enterokine FGF19 that represses bile acid synthesis. Hence, we speculate that the FGFR4 variant interferes with the enterohepatic FGF19 feedback loop and thus predisposes to ICP. This is the first ICP case due to an FGFR4 mutation described to date.

Publication History

Article published online:
04 January 2021