Alagille syndrome is a multisystemic, autosomal dominant disorder caused by a defect in the notch signalling pathway leading to intrahepatic bile duct paucity and resulting in significant cholestasis.1
The prevalence of Alagille syndrome is approximately 1 in 70,000, although the incidence may actually be closer to 1 in 30,000.2Features of the syndrome include characteristic facies, bile duct paucity, chronic cholestasis, and cardiac, renal, vascular, skeletal and ocular system abnormalities.2,3
Diagnosis
- Diagnosis is based on histological evidence of intrahepatic bile duct paucity leading to chronic cholestasis and at least two other clinical features2,4
- Cardiac disease (stenosis of the branches of the pulmonary artery or other malformations)
- Ocular abnormalities (a posterior embryotoxon: white retrocorneal ring parallel to the limbus, identified by slit-lamp examination)
- Skeletal abnormalities (butterfly vertebrae on a dorsal spine X-ray)
- Characteristic facial features (prominent forehead, small pointed chin, hypertelorism)
- Imaging (abdominal ultrasound, cholangiography) helps to identify biliary anatomy3
- Screening should be performed for ophthalmic, skeletal, cardiac, vascular and endocrine (thyroid) abnormalities3
- DNA sequencing of the JAG1 and NOTCH2 genes confirms the diagnosis in more than 90% of cases4
1. Jesina D. Alagille syndrome: an overview. Neonatal Netw 2017;36:343-7.
2. Mitchell E, Gilbert M, Loomes KM. Alagille syndrome. Clin Liver Dis 2018;22:625-41.
3. INSERM. Orphanet. European Union: The portal for rare diseases and orphan drugs. 2021 (accessed 09/2021 at https://www.orpha.net/consor/cgi-bin/Disease.php?lng=EN.)
4. Protocole national de diagnostic et de soins : Déficits de synthèse des acides biliaires primaires. Centre de Référence Coordonnateur de l’Atrésie des Voies Biliaires et des Cholestases Génétiques; 2019.
