Alagille syndrome diagnosis overview

The diagnosis is primarily clinical .Sequence analysis of JAG1 detects mutation in 90% of individuals with symptoms. Around 7% of affected individuals have microdeletion of 20p12. Mutations in NOTCH2 is found in less than 1%. If family-specific mutation is known, molecular genetic testing is offered to first-degree relatives. Prenatal testing for pregnancies at increased risk is possible if the JAG1 or NOTCH2 disease-causing mutation in an affected family member is known. Prenatal testing cannot predict the occurrence or severity of clinical manifestations.

The severity of the disorder 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. The major clinical feature is due to cholestasis, due to bile duct paucity as seen on liver biopsy. Congenital heart defect, mostly pulmonary stenosis, typical facial features, skeletal features and posterior embryotoxon in the eye are commonly found. Renal and central nervous system abnormalities may occur.