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

Alagille syndrome (ALGS) is a multisystem disorder, most often caused by JAG1 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 JAG1 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.