Alagille Syndrome - Pathophysiology

Pathophysiology

Microdeletion of the 20p12 gene corresponding to JAG1 results in Alagille syndrome, similar to the inheritance pattern of Williams syndrome. The JAG1 gene is involved in signaling between adjacent cells during embryonic development. This signaling influences how the cells are used to build body structures in the developing embryo. Mutations in JAG1 disrupt the signaling pathway, causing errors in development, especially of the heart, bile ducts in the liver, spinal column, eyes, blood vessels and certain facial features.

NOTCH2 is also associated with Alagille syndrome.

Narrowed and malformed bile ducts in the liver produce many of the health problems associated with Alagille syndrome. Bile is produced in the liver and moves through the bile ducts into the small intestine, where it helps to digest fat. In Alagille syndrome, the bile builds up in the liver and causes scarring that prevents the liver from working properly to eliminate wastes from the bloodstream.