variants in childhood glaucoma: Phenotypic expansion and clinical experience.

PURPOSE

This study describes a distinct spectrum of latent transforming growth factor-β-binding protein 2 ()-related ocular phenotypes in pediatric glaucoma with supporting genetic evidence and highlights our clinical experiences in its management.

METHODS

A total of 189 children with childhood glaucoma underwent whole-exome sequencing-based genetic testing. Of these, 24 children displayed -related phenotypes, among whom 18 cases who tested positive for variants were included in the study. The identified variants were confirmed through Sanger sequencing whenever possible and analyzed using in silico tools. The clinical presentation, genetic variants, and management of these 18 cases were thoroughly reviewed and presented.

RESULTS

All 36 eyes of the 18 children with biallelic variants exhibited megalocornea without Descemet break, iridodonesis, and ectopia lentis. Pupillary changes were noted in all eyes, with persistent pupillary membrane in 78% (28/36) and ectropion uveae in 19% (7/36) eyes. Secondary glaucoma was observed in 72% (26/36) eyes, requiring surgery in 13 of these. Retinal pathology was noted in 47% (17/36) eyes. Lensectomy was performed in 94% (34/36) eyes with a mean age of 4.09 ± 3.5 years. Logistic regression analysis suggested that older age at lensectomy increased the risk of secondary glaucoma (hazard ratio, 1.69; [95% Confidence Interval: 1.00, 2.86], < 0.05). The identified variants included five stop-gain variations, six frameshift variations, and one substitution variation, with five being novel and seven classified as rare variants.

CONCLUSIONS

The study expands the classic -related phenotype spectrum in an Indian pediatric glaucoma cohort, highlighting additional features such as persistent pupillary membrane, ectropion uveae, and associated retinal pathology. These ocular manifestations were predominantly linked to nonsense variants. From a management standpoint, early lensectomy can help prevent secondary glaucoma, while timely identification and treatment of peripheral retinal pathology can reduce the risk of sight-threatening complications.