5 Arteriohepatic dysplasia (Alagille syndrome; Watson-Alagille syndrome)

Alagille syndrome (AS) (arteriohepatic dysplasia, Alagille-Watson syndrome) is a multisystem disorder with hepatic, skeletal, eye, cardiac and renal manifestations. It results from mutation of the JAGI gene, located on chromosome 20, which encodes a ligand for Notch receptor(s). The interactions of Notch receptors and their ligands are crucial in controlling cell fate decisions in a variety of developmental processes. AS varies in its severity, even in the same family, from asymptomatic gene carriers through to lethality due to inoperable cardiac or end-stage liver disease. However, advances in medical and surgical therapy have improved the prognosis at the severe end of the spectrum. It is hoped that the enhanced understanding of the biology of AS resulting from the cloning of the JAGI gene will enable us to develop additional strategies for more effective treatments.