Aniridia is the absence of the iris, a muscular structure that opens and closes the pupil to allow light into the eye. It is also responsible for eye color. Without it, the central eye appears all black. It can be congenital, in which both eyes are usually involved, or caused by a penetrant injury.[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.[2] Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications: nystagmus, amblyopia, buphthalmos, and cataract.[1] 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).
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 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).[3] 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 sustain severe brain damage.[4]
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.
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. [5]
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)
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. 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.[7]
^ abLang, K (2007). Ophthalmology: A Pocket Textbook Atlas (2nd ed.). Thieme. p. 208. ISBN978-1-58890-555-0.
^Singh, Daljit; Arun Verma (17 January 2008). "Aniridia". eMedicine. Retrieved 2 February 2010.
^Lee H, Khan R, O'Keefe M (November 2008). "Aniridia: current pathology and management". Acta Ophthalmol. 86 (7): 708–15. doi:10.1111/j.1755-3768.2008.01427.x. PMID 18937825. S2CID 2476524.
^Gehring, W. J. (2001). "The genetic control of eye development and its implications for the evolution of various eye-types". Zoology. 104 (3–4): 171–181. doi:10.1078/0944-2006-00022. PMID 16351831.
^Neethirajan G, Solomon A, Krishnadas SR, Vijayalakshmi P, Sundaresan P (2009). "Genotype/phenotype association in Indian congenital aniridia". Indian J Pediatr. 76 (5): 513–517. doi:10.1007/s12098-009-0075-4. PMID 19390808. S2CID 29062682.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^"FDA OKs First Artificial Iris for Aniridia, Other Iris Defects". Medscape.
External links
GeneReviews/NCBI/NIH/UW entry on Aniridia
NCBI/Molecular diagnosis of aniridia
OMIM entries on Aniridia
GeneReviews/NIH/NCBI/UW entry on Wilms Tumor Overview
Wikimedia Commons has media related to Aniridia.
March 08, 2023
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This article may be too technical for most readers to understand Please help improve it to make it understandable to non experts without removing the technical details February 2015 Learn how and when to remove this template message Aniridia is the absence of the iris a muscular structure that opens and closes the pupil to allow light into the eye It is also responsible for eye color Without it the central eye appears all black It can be congenital in which both eyes are usually involved or caused by a penetrant injury 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 2 Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications nystagmus amblyopia buphthalmos and cataract 1 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 AniridiaA man with aniridiaSpecialtyMedical genetics Contents 1 PAX6 2 Types 3 Mutational analysis 4 Symptoms 5 Treatment 6 See also 7 References 8 External linksPAX6 Edit 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 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 3 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 sustain severe brain damage 4 Types EditAniridia 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 Online Mendelian Inheritance in Man OMIM 106210 AN Online Mendelian Inheritance in Man OMIM 106220 Aniridia and absent patella Online Mendelian Inheritance in Man OMIM 106230 Aniridia microcornea and spontaneously reabsorbed cataract Online Mendelian Inheritance in Man OMIM 206700 Aniridia cerebellar ataxia and mental deficiency Gillespie syndrome Mutational analysis EditMolecular 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 5 Symptoms EditAniridia 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 don t line up strabismus 6 Treatment EditIn 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 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 7 See also EditWAGR syndrome Scleral lensesReferences Edit a b Lang K 2007 Ophthalmology A Pocket Textbook Atlas 2nd ed Thieme p 208 ISBN 978 1 58890 555 0 Singh Daljit Arun Verma 17 January 2008 Aniridia eMedicine Retrieved 2 February 2010 Lee H Khan R O Keefe M November 2008 Aniridia current pathology and management Acta Ophthalmol 86 7 708 15 doi 10 1111 j 1755 3768 2008 01427 x PMID 18937825 S2CID 2476524 Gehring W J 2001 The genetic control of eye development and its implications for the evolution of various eye types Zoology 104 3 4 171 181 doi 10 1078 0944 2006 00022 PMID 16351831 Neethirajan G Solomon A Krishnadas SR Vijayalakshmi P Sundaresan P 2009 Genotype phenotype association in Indian congenital aniridia Indian J Pediatr 76 5 513 517 doi 10 1007 s12098 009 0075 4 PMID 19390808 S2CID 29062682 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Articles Cedars Sinai Retrieved 2022 02 10 FDA OKs First Artificial Iris for Aniridia Other Iris Defects Medscape External links EditGeneReviews NCBI NIH UW entry on Aniridia NCBI Molecular diagnosis of aniridia OMIM entries on Aniridia GeneReviews NIH NCBI UW entry on Wilms Tumor Overview Wikimedia Commons has media related to Aniridia Retrieved from https en wikipedia org w index php title Aniridia amp oldid 1136108910, wikipedia, wiki, book, books, library,
