What is Aniridia
Aniridia is a congenital disease characterized by the complete or partial absence of the iris. The condition can be hereditary, sporadic or be part of a syndrome.
Aniridia is not limited to a developmental defect of the iris, but is often associated with a series of ocular complications present since birth or late onset: reduction of visual acuity, macular hypoplasia and optic nerve, nystagmus, amblyopia, cataracts and corneal changes.
Causes
Aniridia is caused by a genetic alteration affecting the AN2 region of the short arm of chromosome 11 (11p13), which includes the PAX6 gene, or by deletion of the sequences that control its expression. PAX6 provides instructions that regulate a cascade of other events involved in the early development of the eye and other non-ocular structures, such as the brain, spinal cord and pancreas.
The clinical expression of the disease is variable and depends on the type of alteration affecting the 11p13 region (mutation, deletion, translocation, insertion, etc.). Some defects seem to inhibit the function of PAX6 protein products more, while others provide sufficient gene expression to produce a mild phenotype.
Aniridia isolated. The disease can manifest itself, for the first time, in a child born of non-carrier parents. Sporadic mutations, which cause the onset of aniridia, can occur without systemic involvement, due to de novo deletions on chromosome 11p13.
Syndromic aniridia. In a minority of cases, if the genetic defect affects the WT1 region, adjacent to the AN2 region, the disease may present in the context of a syndrome and is associated with other non-ocular abnormalities, such as the nephroblastoma (Wilms tumor) or other defects of development.
Consequences on vision
Aniridia has a variable degree of hypoplasia (incomplete development), up to the absence of the iris in both eyes, associated with other more or less serious ocular characteristics:
- The pupil, very large or deformed, determines hypersensitivity to light and glare.
- The vascularization and opacity of the cornea can cause defects in light refraction.
- Cataract (lens opacity) occurs in 50-80% of patients and can alter vision.
- The crystalline lens can be subluxated (moved from the normal seat).
- Poor development of the fovea (central area of the retina of maximum visual acuity) or of the optic nerve can cause nystagmus and reduced vision.
- Over 50% of people with aniridia develop glaucoma (high intraocular pressure, which can produce permanent damage to the retina and the optic nerve).
Other health problems
Aniridia can occur without implications for other body systems or as part of a syndrome (a group of signs that occur constantly together).
- In Miller syndrome, aniridia is associated with a malignant neoplasm of the kidney: Wilms' tumor (nephroblastoma).
- Gillespie syndrome is a combination of aniridia, mental retardation and balance problems (cerebellar ataxia).
- WAGR syndrome is manifested by aniridia, genital anomalies, mental retardation and Wilms tumor.
Diagnosis and Treatment
The main diagnostic feature of aniridia is the partial or total absence of the iris; foveal hypoplasia, with reduced visual acuity, is almost always present and is associated with the early onset of nystagmus. Other ocular anomalies, generally with late onset, determine further reduction of visual function and must be monitored carefully. These conditions include: cataract, glaucoma and corneal opacification. Once aniridia has been diagnosed, periodic eye exams are therefore required, often for life. The frequency of visits depends on the clinical expression and the extent of the disorder. In children with a deletion of the PAX6 gene, monitoring of renal function and frequent ultrasound checks is recommended.
The therapeutic approach is aimed at improving visual acuity and pharmacologically or surgery to manage any complications associated with aniridia. The prescription of glasses can correct refractive errors. The use of colored or photochromic vision lenses is instead useful to avoid glare and reduce hypersensitivity to light.
