Case Report: Novel

Background: Juvenile-onset open-angle glaucoma (JOAG) is a heterogeneous early-onset glaucoma subtype. Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder caused by Methods: A 15-year-old male proband and his family members received detailed ophthalmic and systemic evaluations. Whole-exome sequencing was performed in the proband, and candidate variants were verified by Sanger sequencing. Bioinformatic tools were used to evaluate variant pathogenicity. Results: The proband and his elder sister initially presented with severe early-onset glaucoma and were diagnosed with JOAG at an outside hospital. After systemic evaluation, they were found to have anterior segment dysgenesis and characteristic facial features, including midface hypoplasia, hypertelorism, and saddle nose deformity, supporting a revised diagnosis of ARS. A novel heterozygous missense variant c.311T>G (p.Ile104Ser) in Conclusion: We identified a novel FOXC1 variant responsible for ARS in a Chinese family. ARS-associated glaucoma can closely mimic JOAG, leading to initial misdiagnosis. The observation of incomplete penetrance in an unaffected carrier father underscores the phenotypic complexity of this disorder. Our findings expand the genotypic spectrum of FOXC1-related disorders and highlight the importance of systemic evaluation and genetic testing in patients with early-onset glaucoma.