Alagille syndrome is predominately caused by changes in a gene called Jagged1 located on chromosome 20. In 3 to 5 percent of cases, the entire gene is deleted (missing) from one copy of chromosome 20. In the majority of cases of Alagille syndrome, there are changes or mutations in the DNA sequence that makes up the Jagged1 gene. In a very small number of cases, less than 1 percent, changes in another gene, Notch 2, result in Alagille Syndrome.
About one-third of children with Alagille syndrome inherit the change in Jagged1 from a parent. In the remaining two-thirds of cases, the mutation in Jagged1 is a new one in that child. Alagille syndrome is an autosomal dominant disorder, which means someone who carries the Jagged1 gene mutation has a 50 percent chance of passing on that mutation to their child.
The effect of having a mutation in Jagged1 can vary widely. Some individuals who inherit a mutation have severe Alagille syndrome, involving heart and liver disease, while others experience only minor manifestations, such as posterior embryotoxon or characteristic facial features.
Reviewed by: Binita M. Kamath, MD
Date: January 2009