Anterior Segment Dysgenesis (ASD) encompasses a heterogeneous group of congenital ocular malformations resulting from disrupted differentiation of neural crest–derived tissues. These disorders frequently lead to developmental glaucoma, a major cause of childhood blindness. This review summarizes the current clinical, genetic, and management perspectives on ASD associated with glaucoma.
Methods
A comprehensive literature search of PubMed, Scopus, and Web of Science (January 2000–August 2025) identified 186 relevant studies reporting clinical, molecular, and therapeutic findings. Data were synthesized across major ASD subtypes: aniridia, Axenfeld–Rieger anomaly, Peters anomaly, primary aphakia, and related entities.
Results
Mutations in key transcriptional and structural genes—including PAX6, FOXC1, PITX2, CYP1B1, LTBP2, PXDN, and GJA8—account for the majority of ASD cases. Novel associations involving CPAMD8, JAG1, and ADAMTS18 have broadened the known genetic spectrum. Genotype–phenotype correlations explain the variability in glaucoma onset and treatment response among subtypes. Modern diagnostic strategies integrating anterior segment imaging with next-generation sequencing have improved early detection and prognostic accuracy. Management requires individualized surgical and medical approaches based on the underlying genetic mechanism.
Conclusion
ASD-associated glaucoma exemplifies the interface between developmental genetics and clinical ophthalmology. Understanding gene-specific mechanisms aids precision diagnosis, risk stratification, and multidisciplinary care. Continued advances in molecular diagnostics and targeted therapies promise to transform outcomes for children with congenital anterior segment anomalies. Collaborative registries and functional genomics will be pivotal in translating molecular discoveries into targeted therapies and improved lifelong vision outcomes.
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