Congenital glaucoma associated with high hyperopia, an ophthalmic phenotypical manifestation for GLIS3 deletion: case report and review of literature.

Background: GLI-Similar 3 (GLIS3) gene plays a critical role in the regulation of several biological processes and is implicated in the development of various diseases. However, documentation regarding congenital glaucoma and other ophthalmic features in patients with GLIS3 variants is lacking. We aimed to expand the ophthalmological features related to GLIS3 deletion.

Methods: We present a case report of two Saudi Arabian siblings with congenital glaucoma, congenital diabetes mellitus, and congenital hypothyroidism. Full ophthalmological examination, medical evaluation, and genetic testing of all family members were conducted.

Results: In both patients, ophthalmic assessments revealed congenital glaucoma, high hyperopia, and short axial length of the globe. Genetic testing confirmed the presence of a large homozygous deletion, including the non-coding exon 1 and the entire coding exon 2 of the GLIS3 gene. Endocrine abnormalities included neonatal diabetes, congenital hypothyroidism, along with characteristic facial features that shows a long philtrum and thin and tight upper lip. Genetic testing of other siblings showed a heterozygous deletion of the GLIS3 gene. Although their ophthalmic examinations were unremarkable, all carriers presented with juvenile hypothyroidism.

Conclusion: Congenital glaucoma is commonly associated with myopia. We report an association between congenital glaucoma and high hyperopia related to GLIS3 partial deletion, which to our knowledge, has not been previously reported. We recommend that pediatric patients with neonatal diabetes and hypothyroidism to be evaluated for congenital glaucoma. Additionally, we suggest screening carriers for hypothyroidism.