Alagille Syndrome

Background and History: 

Alagille syndrome has been recognized since the 1970's and was first reported as a syndromic form of liver disease.  Cases have been found from around the world although it is a relatively rare inherited disorder.  The facial features are considered by some to be sufficiently characteristic to enable a presumptive visual diagnosis.

Clinical Correlations: 

The clinical combination of liver disease, eye abnormalities, a characteristic facial appearance, and vascular disease suggests the presence of this disorder.  The liver disease results in jaundice as the bile ducts do not develop normally. Changes in the pigmentation of the retina and sometimes pupil abnormalities in the eye may be associated with a broad forehead, a pointed chin and a large nose.  Fingers and toes may appear short and short stature is common as well.  The vertebrae may have a distinctive 'butterfly' appearance on X-ray.  The major blood vessels are often abnormal as well with enlargements and blockages and these are among the most serious health threats.  Heart murmurs are common.

The eye changes generally do not cause a vision problem.

Genetics: 

Alagille syndrome is caused by a mutation in a gene located on chromosome 20, called JAG1.  It is an autosomal dominant disorder, meaning it can be inherited from a parent with the same disease.  The clinical features, though, are highly variable from one person to the next.

Diagnosis and Prognosis: 

The diagnosis requires a thorough evaluation of multiple organs including the liver, eye, bones, and heart system.  Ultimately, a gene test is required to obtain a precise confirmation.  The greatest threat to good health results from blood vessel and heart disease.  Liver failure can be treated with a liver transplant in some cases.  Most individuals with this syndrome live to at least 20 years of age and the prognosis is improving as better organ treatments are developed.

Additional Information