Alagille Syndrome

What is Alagille syndrome?

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

Signs and symptoms arising from liver damage in Alagille syndrome may include a yellowish tinge in the skin and the whites of the eyes (jaundice), itching, and deposits of cholesterol in the skin (xanthomas). A liver biopsy may indicate too few bile ducts (bile duct paucity). These ducts carry bile (which helps to digest fats) from the liver to the gallbladder and small intestine.

Other signs of Alagille syndrome include congenital heart problems and an unusual butterfly shape of the bones of the spinal column that can be seen in an x-ray.

Facial features characteristic of Alagille syndrome include a broad, prominent forehead, deep-set eyes, and a small pointed chin. The disorder may also affect the kidneys and central nervous system.

Problems associated with Alagille syndrome generally become evident in infancy or early childhood. The severity of the disorder, however, can vary within the same family, with symptoms ranging from so mild as to go unnoticed to severe heart and/or liver disease requiring transplantation.

Some people with Alagille syndrome may have only the characteristic facial features or isolated problems such as a heart defect called tetralogy of Fallot. These individuals do not have liver disease or other features typical of the disorder.

How common is Alagille syndrome?

The estimated prevalence of Alagille syndrome is 1 in every 70,000 people. This figure is based on diagnoses of liver disease in infancy, and may be an underestimation due to the varying severity and symptoms of the disorder.

What genes are related to Alagille syndrome?

Mutations in the JAG1 gene cause Alagille syndrome.

The JAG1 gene is involved in signaling between adjacent cells during embryonic development. This signaling influences how the cells are used to build body structures in the developing embryo. Mutations in JAG1 disrupt the signaling pathway, causing errors in development, especially of the heart, bile ducts in the liver, spinal column, and certain facial features.

Narrowed and malformed bile ducts in the liver produce many of the health problems associated with Alagille syndrome. Bile is produced in the liver and moves through the bile ducts into the small intestine, where it helps to digest fat. In Alagille syndrome, the bile builds up in the liver and causes scarring that prevents the liver from working properly to eliminate wastes from the bloodstream.

How do people inherit Alagille syndrome?

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

In approximately 30 percent to 50 percent of cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.

What other names do people use for Alagille syndrome?

  • Alagille-Watson Syndrome
  • arteriohepatic dysplasia (AHD)
  • cardiovertebral syndrome
  • cholestasis with peripheral pulmonary stenosis
  • hepatic ductular hypoplasia
  • hepatofacioneurocardiovertebral syndrome
  • paucity of interlobular bile ducts
  • Watson-Miller syndrome

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