PAX6 mutation in association with ptosis, cataract, iris hypoplasia, corneal opacification and diabetes: A new variant of familial aniridia?

Background: We report a family with ptosis, cataract, iris hypoplasia and gradual corneal opacification occurring in association with a PAX6 mutation. Design: Case-series. Participants: Fourteen family members - 8 affected, 6 unaffected controls. Methods: All participants underwent ophthalmological assessment, including best-corrected visual acuity, slit-lamp-examination, pachymetry, endothelial cell-count, tonometry and dilated fundoscopy. All subjects underwent anthropometry and assessment of glycaemic status. Genetic analysis of the PAX6 gene was performed. Main Outcome Measures: Presence of ptosis, corneal, iris and lenticular changes, gycaemic and PAX6 status. Results: All eight affected subjects had ptosis with reduced levator function, anterior polar cataracts, and corneal changes of variable severity - two patients had undergone penetrating keratoplasties, with graft histology revealing conjunctival cells on the cornea and severe fibroinflammatory change. Five patients had iris hypoplasia. One patient had aphakic glaucoma and another had hypoplastic optic discs. Four of the six controls had no ocular features of this syndrome, and two had isolated mild ptosis. There was no difference in height or body mass index between cases and family controls (p>0.05), but Haemoglobin A1c was greater in the cases (median [interquartile range] 5.6(0.8) vs 5.1(0.3), p=0.028). Genetic analysis confirmed a pathogenic PAX6 mutation in exon 12 (c1439delC) in all eight patients, but none of the controls. Conclusion: This is the first report of this particular constellation of ocular signs occurring in association with a PAX6 mutation. There was no association with anthropometric features, but affected subjects had worse glycaemia than controls, which may be related to the known role of PAX6 in development of the pancreas. © 2013 Royal Australian and New Zealand College of Ophthalmologists.