Alagille syndrome is a rare genetic disorder that affects multiple systems in the body. The five major signs and symptoms associated with Alagille syndrome are problems with the bile ducts, which carry bile from the liver to the gallbladder and small intestine to help digest fats, narrowing of the main artery from the heart to the lungs, abnormal vertebrae, eye problems, and characteristic facial features. People with three of these five main signs are considered to have the syndrome. Additional signs and symptoms may involve the veins, bones, ears, pancreas, kidney, and intestine. Symptoms may vary widely among patients, even among members of the same family.
Alagille syndrome is caused by mutations or defects in the JAG1 and NOTCH2 genes. Mutations in the JAG1 gene cause the majority of cases, while mutations in the NOTCH2 gene cause fewer than 1% of cases. These genes provide the instructions for making proteins that play a role in communication between cells during fetal development. The mutations disrupt this communication and cause errors in development.
Alagille syndrome is inherited, or passed down from parent to child. The syndrome follows an autosomal dominant pattern of inheritance, meaning that only one copy of the defective gene is necessary for the disease to appear. There are about 226 genetic mutations, or abnormalities, associated with Alagille syndrome. About 70% of cases of Alagille syndrome are associated with known mutations. About 30% of cases of Alagille syndrome, however, have unknown causes. In about 30-50% of cases of Alagille syndrome, a person inherits the disorder from a parent. The remaining cases appear to result from a spontaneous mutation in the egg or sperm cells or in the developing embryo.
The incidence of Alagille syndrome is estimated to be about one in 70,000 live births worldwide. Some researchers state that the incidence may be higher due to unreported cases of the disease. Others estimate that the prevalence may be as high as one in 20,000 live births. Alagille syndrome appears to affect males and females in equal numbers. No particular race or ethnic group appears to be affected more than any other.
People are often diagnosed with Alagille syndrome early in life, when symptoms are first apparent. About 10% of people with Alagille syndrome die from complications of the disease. This may be caused by severe heart or liver disease early in life, or by heart attack or stroke later in life.
There is no cure for Alagille syndrome. Treatment focuses on reduction of symptoms and prevention and management of complications. If managed properly, most people with Alagille syndrome can have normal life spans.
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