Brittle Cornea Syndrome Type 1 in Siblings: Severe Presentation in One and Misdiagnosis as Primary Congenital Glaucoma in the Other.

Abstract

Purpose: The purpose of this study was to present two cases of brittle cornea syndrome (BCS) in siblings, one with severe corneal perforation and the other misdiagnosed as primary congenital glaucoma, emphasizing clinical, histopathological, and genetic findings.

Methods: This was a case report involving a 4-year-old boy and his 8-year-old brother, both presenting with thin, steep corneas. Clinical examination, Pentacam imaging, genetic analysis, systemic evaluation, and corneal histopathology were performed.

Results: The younger sibling presented with corneal perforation after trauma, and histopathology revealed a markedly thinned corneal stroma with disrupted collagen architecture. Genetic testing confirmed a zinc finger protein (ZNF)469 mutation, consistent with brittle cornea syndrome type 1 (BCS1). Sanger sequencing of the older sibling, who was previously misdiagnosed with primary congenital glaucoma, identified the same ZNF469 mutation. He exhibited corneal thinning, bluish sclera, and healthy optic discs.

Conclusions: These cases highlight the variability in BCS presentations, the risk of misdiagnosis as glaucoma, and the importance of early genetic testing and protective measures. Histopathological findings provide additional insights into the structural abnormalities in BCS corneas.