Alagille syndrome

Disease Overview

Alagille syndrome is a genetic syndrome that can affect the liver and other parts of the body. The liver problems result from having fewer small bile ducts than normal in the liver. This leads to bile building-up inside the liver, which in turn causes liver scarring and damage.[2141] Signs and symptoms of Alagille syndrome are generally noticed in infancy or early childhood. Type of symptoms and severity varies greatly, even among people in the same family, so that in some cases the symptoms are severe, and in others, very mild. The liver problems may be the first symptoms of the syndrome, and may include yellow color of the skin and whites of the eyes (jaundice); itchy skin; bumps on the skin caused by deposits of cholesterol and fats (xanthomas); pale, loose bowel movements; and poor growth. [2141][2142] Alagille syndrome can also affect other parts of the body including the heart, brain, kidneys, blood vessels, eyes, face, and skeleton. People with Alagille syndrome may have distinctive facial features too, including a broad, prominent forehead, deep-set eyes, and a small, pointed chin.[2141]

Alagille syndrome is caused by changes or mutations in the JAG1 and NOTCH2 genes.  Inheritance is autosomal dominant. However, in about half of cases the mutation occurs as a new change (“de novo”) without being inherited from either parents.[2143] While there is no known cure for Alagille syndrome, there are treatments that can help control symptoms. Possible treatments may include medication that increases the flow of bile and careful management of diet to minimize nutrition and vitamin related problems. In severe cases, a liver transplant may be necessary.[2141]

Synonyms

• Hepatic ductular hypoplasia
• Watson Alagille syndrome
• Alagille-Watson syndrome
• Cholestasis with peripheral pulmonary stenosis
• Arteriohepatic dysplasia
• Paucity of interlobular bile ducts
• Cardiovertebral syndrome
• Watson-Miller syndrome
• Hepatofacioneurocardiovertebral syndrome