Alagille syndrome overview

Overview
Alagille syndrome is a multisystem genetic disorder that affects the liver, heart, eyes,face, skeleton, kidneys and vascular system. Problems associated with the disorder generally become evident in infancy or early childhood. The patients have a characteristic facial appearance. The disorder is inherited in an autosomal dominant pattern, and the estimated prevalence of Alagille syndrome is 1 in every 70,000 live births. The clinical features are highly variable even within the family.

Diagnosis
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.

Treatment
There is no known cure for Alagille's Syndrome. Most of the treatments available are aimed at improving the functioning of the heart, and reducing the effects of impaired liver function.