Alagille syndrome is a genetic disorder that can affect the liver, heart, and other parts of the body.

In more than 90 percent of cases, mutations in the JAG1 gene cause Alagille syndrome. Another 7 percent of individuals with Alagille syndrome have small deletions of genetic material on chromosome 20 that include the JAG1 gene. A few people with Alagille syndrome have mutations in a different gene, called NOTCH2. The JAG1 and NOTCH2 genes provide instructions for making proteins that fit together to trigger interactions called Notch signaling between neighboring cells during embryonic development. This signaling influences how the cells are used to build body structures in the developing embryo. Changes in either the JAG1 gene or NOTCH2 gene probably disrupt the Notch signaling pathway. As a result, errors may occur during development, especially affecting the bile ducts, heart, spinal column, and certain facial features.

The estimated prevalence of Alagille syndrome is 1 in 70,000 newborns. This figure is based on diagnoses of liver disease in infants, and may be an underestimation because some people with Alagille syndrome do not develop liver disease during infancy.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered or deleted gene in each cell is sufficient to cause the disorder.

Published Date: December 01, 2014
Published By: National Institutes of Health