Alagille syndrome is clinically highly variable with symptoms in several organ systems, mainly due to intrahepatic bile duct hypoplasia and the resulting cholestasis in the liver. Congenital heart defects, especially pulmonary artery stenosis, as well as vertebral anomalies in the form of butterfly-shaped vertebrae and a posterior embryotoxon in the eye are also seen. Characteristic facial features are found. Morbidity and mortality are mainly determined by the cardiological and hepatic symptoms. A (suspected) diagnosis is primarily made clinically on the basis of a typical combination of characteristics; it can be confirmed by molecular genetic methods by detecting pathogenic variants in the JAG1 or NOTCH2 genes. The vast majority of patients carry pathogenic variants in JAG1, 5-10% of which are caused by microdeletions of all or part of the gene in 20p12. Only about 1-2% of patients carry pathogenic variants in NOTCH2. Familial occurrence is observed in 30-50% of those affected; inheritance is autosomal dominant and the frequency is estimated at 1:30,000.
Spinner et al. 2000 May 19 [Updated 2019 Dec 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020 / Mitchell et al. 2018, Clin Liver Dis 22(4):625 / Jesina 2017, Neonatal Netw 36(6):343 / Saleh et al. 2016, Appl Clin Genet 9:75