Comparison of Anterior Segment Abnormalities in Individuals With FOXC1 and PITX2 Variants

Mallika Prem Senthil, Lachlan S.W. Knight, Deepa Taranath, David A. Mackey, Jonathan B. Ruddle, Mark Y. Chiang, Owen M. Siggs, Emmanuelle Souzeau, Jamie E. Craig

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Axenfeld-Rieger syndrome encompasses a group of developmental disorders affecting the anterior chamber structures of the eye, with associated systemic features in some cases. This study aims to compare the difference in anterior segment phenotypes such as those involving the cornea, iris, lens, and anterior chamber angle between cases with disease-causing sequence variations in FOXC1 and PITX2 . METHODS: This cross-sectional study involved 61 individuals, from 32 families with pathogenic FOXC1 or PITX2 variants, who were registered with the Australian and New Zealand Registry of Advanced Glaucoma. RESULTS: The median age of the cohort was 39 years at the time of last assessment (range 3-85 years; females, 54%). Thirty-two patients had pathogenic variants in the FOXC1 gene, and 29 patients had pathogenic variants in the PITX2 gene. Corneal abnormalities were more common in individuals with FOXC1 variants (18/36, 50%) than those with PITX2 variants (4/25, 16%; P = 0.007). Iris abnormalities such as hypoplasia ( P = 0.008) and pseudopolycoria ( P = 0.001) were more common in individuals with PITX2 variants than those with FOXC1 variants. Glaucoma was present in 72% of participants. Corneal decompensation was positively associated with corneal abnormalities ( P < 0.001), glaucoma surgery ( P = 0.025), and cataract surgery ( P = 0.002). CONCLUSIONS: Corneal abnormalities were more common in individuals with FOXC1 than in those with PITX2 variants and were often associated with early onset glaucoma. These findings highlight that patients with FOXC1 variations require close follow-up and monitoring throughout infancy and into adulthood.

Original languageEnglish
Pages (from-to)1009-1015
Number of pages7
JournalCornea
Volume41
Issue number8
Early online date31 Mar 2022
DOIs
Publication statusPublished - 1 Aug 2022

Keywords

  • Corneal abnormalities
  • Axenfeld–Rieger syndrome
  • anterior segment phenotypes
  • FOXC1 variant
  • PITX2 variant

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