Alagille syndrome

Alagille syndrome (AGS) was described more than 35 years ago as a genetic entity characterised by five major features: chronic cholestasis owing to paucity of interlobular bile ducts; peripheral pulmonary stenosis; butterfly like vertebral arch defect; posterior embryotoxon and peculiar facies. AGS has long been said to have a relative good prognosis but overall survival at twenty years averages 70%. Complex congenital heart disease and hepatic disease with or without liver transplantation contribute significantly to mortality. JAGGED1 has been identified as a responsible gene by demonstration of mutations in AGS patients. Studies of JAGGED1 expression pattern demonstrate that minor features and almost all the elements in the long list of manifestations described in AGS patients are not coincidental. This suggests that Alagille syndrome definition may be revisited in the light of JAGGED1 mutations.