Alagille syndrome is a multisystem disorder possibly affecting :
- liver: chronic cholestasis due to paucity of intrahepatic bile ducts,
- heart: peripheral pulmonary artery stenosis and/or other heart defects,
- vertebrae: minor vertebral segmentation anomalies,
- face: characteristic facies,
- eye: posterior embryotoxon /anterior segment abnormalities of the eye, pigmentary retinopathy, and
- kidney: dysplastic kidneys.
The cause is an abnormality in components of the Notch signalling pathway, most commonly due to a mutation in JAG1 (ALGS type 1), and in a small proportion of cases mutation in NOTCH2 (ALGS type 2). It follows autosomal dominant inheritance, but reduced penetrance and variable expression are common in this disorder, and somatic/germline mosaicism may also be relatively frequent.