User:Ehubbard3/aniridia

Aniridia is the absence of the iris, usually involving both eyes. It can be congenital or caused by a penetrant injury. Isolated aniridia is a congenital disorder which is not limited to a defect in iris development, but is a  panocular condition with macular and optic nerve hypoplasia, cataract,  and corneal changes. Vision may be severely compromised and the disorder is frequently  associated with a number of ocular complications: nystagmus, amblyopia, buphthalmos, and cataract. Aniridia in some individuals is associated with kidney nephroblastoma (Wilms tumor), genitourinary anomalies, or intellectual disability and cerebellar ataxia (Gillespie syndrome), resulting in the WAGR syndrome.

Signs and symptoms
Because aniridia is characterized by complete or partial absence of the iris, many symptoms relate to eye and vision problems. Symptoms includes misshapen pupils, reduction in vision sharpness, increased sensitivity to light, increased pressure in the eye (glaucoma), clouding of the eyes (cataracts), underdeveloped optic nerves, and involuntary eye movements (nystagmus).

Many individuals affected by aniridia display one or more symptoms mentioned above, but rarely do they display all the symptoms. Cataracts occur in about 50-85% of individuals, while about 10% of people have underdeveloped optic nerves. Visual acuity usually falls between 20/80 and 20/200, with some individuals with good enough vision to drive while others being legally blind. Rarely behavioral and developmental issues are also present.

Aniridia is usually diagnosed through clinical examination and confirmed through genetic testing.

Treatment and Prognosis
Aniridia is a nonlethal disease, and is usually treated by treating the symptoms of the disease. Aniridia is treated with spectacle correction of refractive errors, tinted or photochromic lenses to reduce light sensitivity, occlusion therapy for amblyopia, and low-vision aids such as closed-circuit television. In children, care is taken to increase visual contract in their surrounding to ensure proper eye development.

Other indirect symptoms can also be treated. Cataract extraction may improve visual acuity in those with dense cataracts. Glaucoma is initially treated with topical anti-glaucoma medication; refractory cases may require surgery (trabeculectomy or drainage tube surgery) or cyclodiode treatment. Corneal disease is treated with lubricants, mucolytics, and punctal occlusion. For severe disease corneo-limbal transplant surgery can be undertaken but carries a high risk of failure and may require lifelong systemic immunosuppression. The rare aniridic fibrosis syndrome is treated with surgery.

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 human evolutionary development 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 heterozygous disorder, 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) leads to loss of the eyes and nose and the murine fetuses suffer 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 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).

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)

Mutational Analysis
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.

Epidemiology
Aniridia occurs in 1 in 50,000 to 100,000 newborns worldwide.

History
The disorder has been known since the early 19th century.