Aniridia

Synonyms

1

Overview

Aniridia is an eye disorder characterized by a complete or partial absence of the colored part of the eye (the iris). These iris abnormalities may cause the pupils to be abnormal or misshapen. Aniridia can cause reduction in the sharpness of vision (visual acuity) and increased sensitivity to light (photophobia).

People with aniridia can also have other eye problems. Increased pressure in the eye (glaucoma) typically appears in late childhood or early adolescence. Clouding of the lens of the eye (cataracts), occur in 50 percent to 85 percent of people with aniridia. In about 10 percent of affected people, the structures that carry information from the eyes to the brain (optic nerves) are underdeveloped. Individuals with aniridia may also have involuntary eye movements (nystagmus) or underdevelopment of the region at the back of the eye responsible for sharp central vision (foveal hypoplasia). Many of these eye problems contribute to progressive vision loss in affected individuals. The severity of symptoms is typically the same in both eyes. Rarely, people with aniridia have behavioral problems, developmental delay, and problems detecting odors.

Aniridia may occur either as an isolated eye abnormality or as part of the Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome, genitourinary anomlies and intellectual disability), or Gillespie syndrome (cerebellar ataxia).

Aniridia may be broadly divided into hereditary and sporadic forms. Hereditary aniridia is usually transmitted in an autosomal dominant manner (each offspring has a 50% chance of being affected), although rare autosomal recessive forms (such as Gillespie syndrome) have also been reported. Sporadic aniridia mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called nephroblastoma (Wilms tumor). These patients often also have genitourinary abnormalities and intellectual disability (WAGR syndrome).

Symptoms

• Abnormality of the macula
• Aplasia/Hypoplasia of the iris
• Nystagmus
• Visual impairment

Causes

Aniridia may be caused by mutations in the PAX6 gene and is inherited in an autosomal dominant pattern. The PAX6 gene provides instructions for making a protein that is involved in the early development of the eyes, brain and spinal cord (central nervous system), and the pancreas.

Mutations in the PAX6 gene result in the production of a nonfunctional PAX6 protein that is unable to bind to DNA and regulate the activity of other genes. A lack of functional PAX6 protein disrupts the formation of the eyes during embryonic development.

Diagnosis

Molecular (DNA) testing for PAX6 gene mutations (by sequencing of the entire coding region and deletion/duplication analysis) is available for isolated aniridia and the Gillespie syndrome. For the WAGR syndrome, high-resolution cytogenetic analysis and fluorescence in situ hybridization (FISH) can be utilized to identify deletions within chromosome band 11p13, where both the PAX6 and WT1 genes are located.

Treatment

In childhood, treatment for aniridia focuses on regular eye examinations including necessary corrective lenses, tinted lenses to reduce light sensitivity, and occlusion therapy to address vision abnormalities. Children with Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome require regular renal ultrasounds, hearing tests and evaluation by a pediatric oncologist. Additional treatment is adapted to each individual depending on the associated complications.

Resources

• NIH
• Genetics Home Reference