Ocular Findings in Siblings With Alagille Syndrome: A Report of Two Cases

Alagille syndrome (ALGS) is a multisystem disorder, most often caused by <i>JAG1</i> variants. Ocular features classically include posterior embryotoxon and optic disc anomalies, but glaucoma is uncommonly reported. We report two Latino siblings with ALGS and glaucoma. They share the previously described <i>JAG1</i> c.925G>C (p.Gly309Arg) variant, classified as a variant of uncertain significance (VUS). One sibling exhibited a posterior embryotoxon, accompanied by retinal nerve fiber layer (RNFL) thinning and elevated intraocular pressure (IOP), which responded to topical therapy. The other had a microcornea, as well as iris and chorioretinal colobomas, with asymmetric cupping and elevated IOP, which was also responsive to topical treatment. The concordant phenotype and shared genotype in these siblings highlight a potential clinical significance, suggesting that disruption of the Notch pathway may increase the risk of anterior-segment (mesodermal) dysgenesis and predispose individuals with ALGS to glaucoma. These cases broaden the recognized spectrum of ALGS phenotypes and underscore the importance of targeted glaucoma screening and longitudinal follow-up, particularly in underrepresented populations.