Aniridia

Abstract

Aniridia is a rare congenital disorder in which there is a variable degree of hypoplasia or the absence of iris tissue associated with multiple other ocular changes, some present from birth and some arising progressively over time. Most cases are associated with dominantly inherited mutations or deletions of the PAX6 gene. This article will review the clinical manifestations, the molecular basis including genotype-phenotype correlations, diagnostic approaches and management of aniridia.

Figure 1

Heterozygous PAX6 mutations cause a range of eye phenotypes. (a) Total absence of iris tissue with surgical aphakia (removal of natural lens) and remnant of opaque lens capsule (CTE mutation). (b) Almost complete absence of iris tissue obscured by peripheral corneal changes with opacification and neovasularisation, and unusual partly pigmented cortical lens opacities (PTC mutation). (c) Partial absence of iris tissue (missense mutation). (d) Severe aniridic keratopathy with total loss of transparency and neovasularisation of the cornea (PTC mutation). (e) Full iris demonstrating substantial area of abnormal iris architecture (missense mutation). Panels (c) and (e) are reproduced from Hingorani et al. Association for Research in Vision and Ophthalmology.

Figure 2

Flow-chart illustrating a suggested strategy for molecular analysis of aniridia cases. The priority is to determine whether there is an underlying WAGR deletion (involving both the PAX6 and WT1 loci), which strongly predisposes to Wilms tumour. In cases where WT1 is not deleted, detection of a PAX6 mutation is less urgent but provides a sound basis for genetic counselling. This diagram is intended to show general principles only – molecular techniques are evolving quickly and the specific approaches mentioned here may be superseded by more efficient and cost-effective methods.