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SpecialtyAniridia_header_cell_0_1_0 Medical genetics Q548719?uselang=en#P1995Aniridia_cell_0_1_1

Aniridia is the absence of the iris, usually involving both eyes. Aniridia_sentence_0

It can be congenital or caused by a penetrant injury. Aniridia_sentence_1

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. Aniridia_sentence_2

Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications: nystagmus, amblyopia, buphthalmos, and cataract. Aniridia_sentence_3

Aniridia in some individuals occurs as part of a syndrome, such as WAGR syndrome (kidney nephroblastoma (Wilms tumour), genitourinary anomalies and intellectual disability), or Gillespie syndrome (cerebellar ataxia). Aniridia_sentence_4

PAX6 Aniridia_section_0

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 non-ocular structures). Aniridia_sentence_5

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. Aniridia_sentence_6

Thus the PAX6 gene is highly conserved across evolutionary lineages. Aniridia_sentence_7

Defects in the PAX6 gene cause aniridia-like ocular defects in mice (as well as Drosophila). Aniridia_sentence_8

Aniridia is a heterozygous disorder, meaning that only one of the two chromosome 11 copies is affected. Aniridia_sentence_9

When both copies are altered (homozygous condition), the result is a uniformly fatal condition with near complete failure of entire eye formation. Aniridia_sentence_10

In 2001, two cases of homozygous aniridia patients were reported; the fetuses died prior to birth and had severe brain damage. Aniridia_sentence_11

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. Aniridia_sentence_12

Types Aniridia_section_1

Aniridia may be broadly divided into hereditary and sporadic forms. Aniridia_sentence_13

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. Aniridia_sentence_14

Sporadic aniridia mutations may affect the WT1 region adjacent to the AN2 aniridia region, causing a kidney cancer called nephroblastoma (Wilms tumor). Aniridia_sentence_15

These patients often also have genitourinary abnormalities and intellectual disability (WAGR syndrome). Aniridia_sentence_16

Several different mutations may affect the PAX6 gene. Aniridia_sentence_17

Some mutations appear to inhibit gene function more than others, with subsequent variability in the severity of the disease. Aniridia_sentence_18

Thus, some aniridic individuals are only missing a relatively small amount of iris, do not have foveal hypoplasia, and retain relatively normal vision. Aniridia_sentence_19

Presumably, the genetic defect in these individuals causes less "heterozygous insufficiency," meaning they retain enough gene function to yield a milder phenotype. Aniridia_sentence_20


Mutational analysis Aniridia_section_2

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. Aniridia_sentence_21

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. Aniridia_sentence_22

Treatment Aniridia_section_3

In May 2018, the U.S. Food and Drug Administration approved the CustomFlex Artificial Iris, the first synthetic iris for use in adults and children with congenital aniridia or iris defects related to other conditions, such as albinism, traumatic injury, or surgical removal due to ocular melanoma. Aniridia_sentence_23

The artificial iris is a surgically implanted device made of thin, foldable, medical-grade silicone and is custom-sized and colored for each individual patient. Aniridia_sentence_24

The prosthetic iris is held in place by the anatomical structures of the eye or, if needed, by sutures. Aniridia_sentence_25

See also Aniridia_section_4


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