NORD gratefully acknowledges Bryan C. Mak, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Summary
Aniridia is a rare condition characterized by abnormal development of the iris of the eye. The iris is the circular, colored part in the middle of the eyeball. The center of the iris is known as the pupil. The iris can control the size of the pupil, which regulates the amount of light that enters the eye. Aniridia is a condition in which the iris is either partly or completely missing. Various forms of aniridia have been identified. Each form can be determined by what additional symptoms are present.
Aniridia is marked by partial or complete absence of the iris of the eye. Vision is preserved in some patients with mild cases of aniridia. This condition occurs when the iris fails to develop normally before birth in one or both eyes. Typically, aniridia can be seen from birth. Aniridia can occur as a single abnormality or can be one of many symptoms in an underlying condition.
Isolated aniridia: Isolated aniridia is the partial or complete absence of the iris from birth. Some people with this type of aniridia may be unaware of any eye problems because pupils appear normal and usually only one eye is mildly affected. In more severe cases, isolated aniridia can cause vision problems later in life. Accompanying symptoms may include clouding of the crystalline lens of the eye (cataracts), gradual loss of vision due to increased pressure inside the eyeball which may be accompanied by varying degrees of pain (glaucoma) or superficial clouding of the cornea (corneal pannus). Rapid involuntary movement of the eyeball (nystagmus) and underdevelopment of the fovea area of the retina (which controls acute vision) may also occur. These accompanying symptoms can make vision cloudy or blurry.
Gillespie syndrome: Symptoms of Gillespie syndrome include aniridia, intellectual disability, and ataxia (lack of coordination of muscle movements). (For more information choose “Gillespie” as your search term in the Rare Disease Database.)
WAGR syndrome: WAGR stands for Wilms’ tumor (a type of kidney tumor), Aniridia, Genitourinary abnormalities, and Retardation (now called “Intellectual disability”). WAGR syndrome can also be associated with obesity. WAGR syndrome can present with some or all of these symptoms. (For more information choose “Wilms” as your search term in the Rare Disease Database.)
Most forms of isolated aniridia are caused by harmful changes (mutations) in the PAX6 gene causing it to not work normally. This condition typically follows an autosomal dominant pattern. Most people with aniridia have a parent with aniridia. Some patients appear to have a spontaneous, new genetic variant.
Gillespie syndrome is a caused by harmful gene changes in in the ITPR1 gene. Gillespie syndrome follows an autosomal dominant pattern, or it can occur as a new genetic change.
WAGR syndrome is mainly caused by missing genetic information along chromosome 11. This missing genetic information sometimes encompasses the PAX6 and WT1 genes. WAGR syndrome gene deletions can occur in a dominant pattern. WAGR syndrome gene deletions can also occur for the first time in the affected individual.
We all have two copies of every gene. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a new changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
Sometimes a genetic cause for aniridia cannot be identified.
All types of aniridia affect males and females in equal numbers. This disorder is thought to occur in approximately 1 in 40,000 to 96,000 live births in the United States.
Treatment
Treatment of aniridia is usually directed at improving and preserving vision. Drugs or surgery may be helpful for glaucoma and/or cataracts. Contact lenses may be beneficial in some cases. When a genetic cause cannot be identified, patients should be evaluated for the possibility of the development of Wilms’ tumor. (For more information on this disorder, please choose “Wilms” as your search term in the Rare Disease Database.)
In 2018, the FDA approved the first artificial iris, a surgically implanted device to treat adults and children with aniridia. This device may help to reduce light sensitivity and glare and improve the cosmetic appearance of the eye.
Genetic counseling is recommended. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected].nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact:
http://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Lauderdale JD. Aniridia. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:640.
REVIEW ARTICLES
Wawrocka A, Krawczynski MR. The genetics of aniridia – simple things become complicated. J Appl Genet. 2018;59(2):151‐159.
Lim H, Kim D, Kim H. PAX6 aniridia syndrome. Curr Opin Ophthalmol. 2017;28(5):436-447.
Hingorani M, Hanson I, van Heyningen V. Aniridia. Eur J Hum Genet. 2012;20(10):1011-1017. doi:10.1038/ejhg.2012.100
JOURNAL ARTICLES
Hall HN, Williamson KA, FitzPatrick DR. The genetic architecture of aniridia and Gillespie syndrome. Hum Genet. 2019;138(8-9):881-898. doi:10.1007/s00439-018-1934-8.
Saying aye to the artificial iris. Nat Biotechnol. 2018;36(7):565.
Sannan NS, Gregory-Evans CY, Lyons CJ, et al. Correlation of novel PAX6 gene abnormalities in aniridia and clinical presentation. Can J Ophthalmol. 2017;52(6):570-577. doi:10.1016/j.jcjo.2017.04.006
Weissbart SB, Ayres BD. Management of aniridia and iris defects: an update on iris prosthesis options. Curr Opin Ophthalmol. 2016;27(3):244-249. doi:10.1097/ICU.0000000000000253
Laghmari M, et al. Bilateral congenital aniridia: 5 case reports. J Fr Ophthalmol. 2004;27:385-91.
Zumkeller W, Orth U, Gal A. Three novel PAX6 mutations in patients with aniridia. Mol Pathol. 2003;56:180-3.
Churchill AJ, et al. Prenatal diagnosis of aniridia. Ophthalmology. 2000;107:1153-56.
Chao LY, et al. Mutation in the PAX6 gene in twenty patients with aniridia. Hum Mutat. 2000;15:332-39.
Hartmann RW Jr, et al. Picture of the month. Congenital aniridia. Arch Pediatr Adolesc Med. 2000;154:525-26.
Tanzer DJ, et al. Black iris-diaphragm intraocular lens for aniridia and aphakia. J Cataract Refract Surg. 1999;25:1548-51.
Osher RH, et al. Cataract surgery combined with implantation of an artifical iris. J Cataract Refract Surg. 1999;25:1540-47.
Chen TC, et al. Goniosurgery for prevention of aniridic glaucoma. Arch Ophthalmol. 1999;117:1144-48.
INTERNET
Moosajee M, Hingorani M, Moore AT. PAX6-Related Aniridia. 2003 May 20 [Updated 2018 Oct 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1360/ Accessed July 22, 2020.
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 106210; Last Update: 10/4/2016. https://www.omim.org/entry/106210# Accessed Jul 22, 2020.
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