JAG1 and congenital heart disease: ALGS is defined clinically by the association of at least three of the five major features: chronic cholestasis, congenital heart disease, skeletal anomalies (typically butterfly vertebra), ocular abnormalities (primarily posterior embryotoxon), and distinct facial features, and genetically by heterozygous mutations in JAG1, or rarely, in NOTCH2 [16–18].