Aniridia (OMIM 106210) is a Panocular developmental malformation with complete or partial Iris hypoplasia being major feature of spectrum.(1) The prevalence of Aniridia (AN) is 1:40,000 to 1:100,000 without any known predilections for sex or gender.(1-3) The spectrum involves not only iris, but also the cornea, lens, optic nerve and fovea.(4)
AN can be familial with Autosomal Dominant Inheritance (AD) in two third of cases, while sporadic in rest of the patients. It can occur as an Isolated Ocular malformation without any systemic involvement or as part of Wilms tumor, Aniridia, Genital Anomalies, Retardation (WAGR) syndrome.(4, 5) AN results from mutations in the Paired Box gene-6 (PAX-6) located on chromosome 11p13, which encodes a highly conserved transcriptional regulator with two DNA binding and a transcriptional trans-activation domain.(6, 7) It is essential for oculogenesis, Central Nervous System (CNS), olfactory system(7) and endocrine glands.(8) Further, it plays multiple roles in development of the cornea, iris, lens and retina during ocular morphogenesis(7, 8) by regulating PAX6 itself, PAX2 , SRY -box 2 (SOX2) gene and a series of retinal transcription factors and structural proteins including crystallins of lens.(9-13) The PAX6 database currently documents 826 total variants and 357 unique DNA sequence changes.(14) Documented mutations in PAX6 include Premature Termination Codon (PTC), C-terminal extensions (CTE) and missense mutations.(14, 15)
Aniridia may be the initial manifestation of WAGR syndrome where deletion of (Wilms tumor 1) WT1 gene deletion in chromosome 11p13 gives rise to the phenotype.(16) WAGR syndrome results from a constitutional complete or partial deletion of 11p13 leading to concurrent deletion of PAX6 gene. This mutation is responsible for the development of Aniridia in association with Wilms tumor.(17) The constellation of features typical of WAGR syndrome includes Wilms tumor (WT), Aniridia, Genitourinary abnormalities and mental retardation.(2, 5)
Visual acuity is reduced in patients with Aniridia and usually ranges between 20/80 to Hand motion.(18) Later, cataract development, glaucoma and progressive keratopathy contribute towards progressive visual deterioration. In addition, Optic nerve hypoplasia and Foveal Hypoplasia, the later causing nystagmus, have been well reported.(1, 6, 18, 19) Myopia is commonest of all refractive errors among Aniridia patients, however; Hypermetropia and Astigmatism may also be seen.(18, 20, 21)
Iris hypoplasia is the key feature of Aniridia however the term Aniridia is a misnomer as the iris is reduced to small stumps, which may be seen on gonioscopy.(18, 22)
In Aniridia patients, congenital lens opacities are commonly seen. Cataracts are rare in infancy but, develop in up to 85% of patients in teens and are associated with a fragile lens capsule. Congenital Aphakia and Lens subluxation are rarely described features in such patients.(1, 6, 18, 23, 24)...