View source for Aniridia

{{short description|Absence of the iris, usually involving both eyes}}{{Infobox medical condition (new)
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| caption         = A man with  aniridia
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'''Aniridia''' is a condition characterized by the absence or near absence of the [[Iris (anatomy)|iris]], the colored, muscular ring in the eye that controls the size of the pupil and regulates the amount of light entering the eye. This absence results in a primarily black appearance of the central eye. Aniridia can be [[Birth defect|congenital]], typically affecting both eyes, or caused by a penetrant injury.<ref name="Lang2">{{cite book |last1=Lang |first1=Gerhard K. |title=Ophthalmology: a pocket textbook atlas |last2=Gareis |first2=O. |date=2007 |publisher=Thieme |isbn=978-1-58890-555-0 |edition=2nd |location=Stuttgart ; New York |page=208}}</ref> Congenital aniridia is not simply an iris defect but a more complex condition affecting multiple parts of the eye, with [[macular hypoplasia|macular]] and [[optic nerve hypoplasia]], [[cataract]], and [[cornea]]l changes.<ref name="eMedicine">{{cite web |last=Singh |first=Daljit |author2=Arun Verma |date=17 January 2008 |title=Aniridia |url=http://emedicine.medscape.com/article/1208379-overview |access-date=2 February 2010 |publisher=eMedicine}}</ref> Vision may be severely compromised and the disorder is frequently associated with several other ocular complications, including [[nystagmus]], [[amblyopia]], [[buphthalmos]], and [[cataract]].<ref name="Lang2" /> In some cases, aniridia occurs as part of a broader syndrome, like [[WAGR syndrome]] ([[Wilms tumour|kidney nephroblastoma]], genitourinary anomalies and intellectual disability) or [[Gillespie syndrome]] ([[cerebellar ataxia]]).

==PAX6==

[[File:Human eyeball with phenotypic expression of aniridia with PAX6 gene mutation.jpg|thumb|right|Phenotypic expression of aniridia with [[PAX6]] gene mutation. The aniridic  probands showed typical features of [[sclerocornea]] with nystagmus in proband 28–1 (A); Foveal hypoplasia in  proband 27–1 (B);  Ptosis, microcornea with dislocated cataractous lens in proband 10–1 (C); Ectopia lentis in  proband 16–1 (D).]]

The [[PAX6]] gene, located within the AN2 region on the short arm of [[chromosome 11]] (11p13), plays a crucial role in the development of the eye and other structures. This gene, named for its "PAired boX" sequence, regulates a cascade of other genetic processes involved in eye formation.<ref>{{cite journal |last1=Lee |first1=Helena |last2=Khan |first2=Rizwana |last3=O’Keefe |first3=Michael |date=November 2008 |title=Aniridia: current pathology and management |journal=Acta Ophthalmologica |volume=86 |issue=7 |pages=708–715 |doi=10.1111/j.1755-3768.2008.01427.x |pmid=18937825 |s2cid=2476524 |doi-access=free}}</ref> Remarkably, the PAX6 gene exhibits high evolutionary conservation, sharing approximately 95% similarity with the ''pax'' gene found in [[zebrafish]], a species whose evolutionary lineage diverged from humans around 400 million years ago.

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 sustain severe brain damage.<ref>{{cite journal |last=Gehring |first=W. J. | date= 2001 |title=The genetic control of eye development and its implications for the evolution of various eye-types |journal=Zoology  |volume=104 |issue=3–4 |pages=171–181 |doi=10.1078/0944-2006-00022 |pmid=16351831 }}</ref>

==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 [[Visual perception|vision]]. Presumably, the genetic defect in these individuals causes less "heterozygous insufficiency," meaning they retain enough gene function to yield a milder [[phenotype]].

*{{OMIM|106210}} AN
*{{OMIM|106220}} Aniridia and absent patella
*{{OMIM|106230}} Aniridia, microcornea, and  spontaneously reabsorbed cataract
*{{OMIM|206700}} 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.<ref>{{cite journal |last1=Neethirajan |first1=Guruswamy |last2=Solomon |first2=Abraham |last3=Krishnadas |first3=Subbaiah Ramasamy |last4=Vijayalakshmi |first4=Perumalsamy |last5=Sundaresan |first5=Periasamy |title=Genotype/phenotype association in Indian congenital aniridia |journal=The Indian Journal of Pediatrics |date=May 2009 |volume=76 |issue=5 |pages=513–517 | pmid = 19390808 | doi = 10.1007/s12098-009-0075-4 | s2cid = 29062682}}</ref>

== Symptoms ==
Aniridia can cause many symptoms, such as:

* Poor vision (not always present)
* More sensitivity to light
* Fast, uncontrolled, shaking "to and from" eye movements ([[nystagmus]])
* Eyes do not line up ([[strabismus]])<ref>{{Cite web|title=Articles|url=https://www.cedars-sinai.org/health-library/articles.html|access-date=2022-02-10|website=Cedars-Sinai|language=en-US|archive-date=2020-05-30|archive-url=https://web.archive.org/web/20200530132825/https://www.cedars-sinai.org/health-library/articles.html|url-status=dead}}</ref>

==Treatment==
In May 2018, the U.S. Food and Drug Administration approved the CustomFlex Artificial Iris, the first [[artificial iris|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]]. 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. The prosthetic iris is held in place by the anatomical structures of the eye or, if needed, by sutures.<ref>{{Cite web|url=http://www.medscape.com/viewarticle/897386|title=FDA OKs First Artificial Iris for Aniridia, Other Iris Defects|website=Medscape}}</ref>

==See also==
*[[WAGR syndrome]]
*[[Scleral lenses]]

==References==
{{Reflist}}
8. Neethirajan G, Hanson IM, Krishnadas SR, Balasubramanian D, Sowdhamini R, Radha V, et al. A novel PAX6 gene mutation in an Indian aniridia patient. Mol Vis. 2003;9:205-9.

9. Neethirajan G, Vijayalakshmi P, Krishnadas SR, Balasubramanian D, Shashikant S, Shashikant C, et al. PAX6 gene variations associated with aniridia in South India. BMC Med Genet. 2004;5:37.

10. Neethirajan G, Collinson JM, Krishnadas SR, Vijayalakshmi P, Soni R, Hanson IM. De novo deletions in the paired domain of PAX6 in south Indian aniridic patients. J Hum Genet. 2004;49(12):647-9.

11. Neethirajan G, Krishnadas SR, Vijayalakshmi P, Anupkumar AN, Balasubramanian D, Hanson IM. Identification of novel mutant PAX6 alleles in Indian cases of familial aniridia. BMC Ophthalmol. 2006;6:28.

12. Neethirajan G, Krishnadas SR, Vijayalakshmi P, Shetty S, Sundaresan P. Semi-Quantitative Analysis of PAX6 Gene in Ocular and Non-Ocular Tissues. New Vis Med Med Sci. 2024;3:47–59

== External links ==
{{Medical resources
|   DiseasesDB      = 723 
|   ICD10          = {{ICD10|Q|13|1|q|10}}  
|   ICD9            = {{ICD9|743.45}} 
|   ICDO            = 
|   OMIM           = 106200 
|   OMIM_mult       = {{OMIM|106210||none}} 
|   MedlinePlus     = 
|   eMedicineSubj  = oph 
|   eMedicineTopic  = 43 
|   MeshID         = D015783 
|   GeneReviewsNBK    = NBK1360 
|   GeneReviewsName = Aniridia
}}

* [https://www.ncbi.nlm.nih.gov/books/NBK1360/  GeneReviews/NCBI/NIH/UW entry on Aniridia]
* [https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=aniridia/  NCBI/Molecular diagnosis of aniridia]
* [https://omim.org/search?index=entry&start=1&limit=10&search=106210+194070+194072+607102+607108+106210+194070+194072+607102+607108&sort=score+desc&field=number  OMIM entries on Aniridia]
* [https://www.ncbi.nlm.nih.gov/books/NBK1294/  GeneReviews/NIH/NCBI/UW entry on Wilms Tumor Overview]
{{Eye pathology}}
{{Congenital malformations and deformations of eye,  ear, face and neck}}

{{commons category|Aniridia}}

[[Category:Congenital disorders of eyes]]