Alagille syndrome

Alagille syndrome is a genetic disorder that primarily damages the liver and heart, though it can also affect the skeleton, eyes, kidneys, and facial structure. It is caused most often by loss-of-function mutations in the JAG1 gene and less often by mutations in the NOTCH2 gene, both of which are essential to the Notch signaling pathway that guides how organs form during embryonic development. In the liver, the syndrome leads to a shortage of small bile ducts, which causes bile to back up and can result in jaundice, itching, and progressive liver damage; the heart is commonly affected by narrowing of the pulmonary arteries or other structural defects. The condition follows an autosomal dominant inheritance pattern, meaning one altered copy of the gene is enough to cause it, and about forty percent of cases are inherited from an affected parent while the rest arise from new mutations. The French pediatrician Daniel Alagille first described the syndrome in 1969, and it is now estimated to occur in about one in every 30,000 to 40,000 live births. With modern medical care roughly ninety percent of affected children survive to adulthood, though the remainder face life-threatening complications, most often from heart or liver failure.