Aniridia

Aniridia is the absence of the iris. This usually occurs in both eyes. It can be congenital or caused by a penetrant injury. Congenital aniridia is not just an isolated defect in iris development but is a  panocular disorder with macular and optic nerve hypoplasia, cataract,  and corneal changes. Vision is severely compromised with the aniridia and the disorder is frequently  associated with a number of complications with the eye: nystagmus, amblyopia, buphthalmos, and cataract.

PAX6


The AN2 region of the short arm of chromosome 11  (11p13) includes the PAX6  gene (named for its PAired boX status), whose gene product helps  regulate a cascade of other genetic processes involved in the  development of the eye (as well as other nonocular structures). This PAX6 gene is around 95% similar to the pax gene found in zebrafish, a creature whose ancestors diverged from the human ancestry around 400 million years ago. Thus the PAX6 gene is highly conserved across evolutionary  lineages.

Defects in the PAX6 gene cause aniridia-like ocular defects in mice  (as well as Drosophila). Aniridia is a heterozygotic disease, meaning that only one of the two chromosome 11 copies is affected. When both copies are altered (homozygous  condition), the result is a uniformly fatal condition with near  complete failure of entire eye formation. In 2001, two cases of homozygous Aniridia patients were reported; the fetuses died prior to  birth and had severe brain damage. In mice, homozygous Small eye defect (mouse Pax-6) led to loss of eyes and nose and the fetuses suffered severe brain damage.

Types
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 rarer 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 mental retardation (WAGR syndrome).

Several different mutations may affect the PAX6 gene. Some mutations appear to inhibit gene function more than others, with subsequent variability in the  severity of the disease. Thus, some aniridic individuals are only missing a relatively small amount of iris, do not have foveal hypoplasia,  and retain relatively normal vision. Presumably, the genetic defect in these individuals causes less "heterozygous insufficiency," meaning they retain enough gene function  to yield a milder phenotype.


 * AN
 * Aniridia and absent patella
 * Aniridia, microcornea, and spontaneously reabsorbed cataract
 * Aniridia, cerebellar ataxia, and mental deficiency (Gillespie syndrome)