Aniridia
Aniridia, meaning "without iris," is a rare congenital disorder marked by the partial or complete absence of the iris, the colored part of the eye that surrounds the pupil. This condition can lead to significant visual impairment and is frequently accompanied by secondary symptoms, including light sensitivity, low vision, lens dislocation, and nystagmus (involuntary eye movement). Aniridia is primarily caused by mutations in the PAX6 gene, which is critical for eye development, with about two-thirds of cases being hereditary and the remainder appearing sporadically. The disorder can manifest alongside other conditions, notably as part of WAGR syndrome, which involves additional health challenges.
Diagnosis typically involves various clinical examinations and genetic testing to determine the presence of PAX6 mutations. While no specific treatments exist for aniridia itself, numerous therapies address its associated complications. These may include low-vision aids, light-blocking devices, and surgical options for related issues like cataracts and glaucoma. Ongoing monitoring and genetic counseling can help manage the condition and its potential impacts on affected individuals and their families.
Aniridia
ALSO KNOWN AS: Irideremia
DEFINITION Aniridia, meaning “without iris,” is a rare congenital disorder characterized by the partial or complete absence of the iris (the colored circular part of the eye that surrounds the pupil). The disorder is frequently associated with secondary symptoms contributing to severe visual impairment.
Risk Factors
No known risk factors exist. According to the American Association for Pediatric Ophthalmology and Strabismus, the prevalence of aniridia is between 1 in 50,000 and 1 in 100,000. The disease affects males and females equally.
Etiology and Genetics
Aniridia is most often caused by a mutation of the PAX6 gene located on chromosome 11 on band 11p13. The PAX6 gene and its product, PAX6 protein, play significant roles in the development of the eye. In aniridics, only one functional copy of the PAX6 gene exists, and as such an insufficient amount of PAX6 protein is made (known as haploinsufficiency), stopping eye development too early and ultimately leading to the incomplete development of the iris.
According to the American Association for Pediatric Ophthalmology and Strabismus (AAPOS) in 2023, in about two-thirds of cases, the disease is familial (passed down from parent to offspring genetically), while in one-third of cases, it is sporadic (noninherited and occurring as a single random case). Some sporadic cases of aniridia are caused by larger chromosome deletions that affect not only the PAX6 gene but also adjacent regions on 11p13. In these cases, aniridia is either an isolated symptom or occurs as part of Wilms’ tumor-aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome, in which more extensive deletions affecting the nearby Wilms tumor locus (WT1) occur.
Familial aniridia is usually transmitted as an autosomal dominant trait, meaning that only one defective PAX6 gene on an autosomal chromosome (non-sex chromosome) needs to be passed down for aniridia to be expressed. Very rarely, aniridia is inherited as an autosomal recessive trait, in which two copies of another defective gene are passed down. In these cases, the disorder is inherited as part of an unusual association of aniridia, cerebellar ataxia, and mental deficiency (Gillespie syndrome), and the underlying genetic defect is not linked to a PAX6 gene mutation.
Symptoms
In unaffected individuals, the iris controls the amount of light let into the eye by opening and closing like the lens of a camera. The inability to control light entry because of partial or complete lack of an iris makes aniridics very light-sensitive. Secondary conditions associated with aniridia include low vision (visual acuity of 20/200, considered legal blindness), lens dislocation, nystagmus (constant involuntary movement of the eyeball). Glaucoma (elevated pressure in the eyeball) occurs in as many as two-thirds of cases, usually occurring during the teenage or adult years, according to Hingorani and Moore. Additional secondary conditions include cataracts (clouding in the lens of the eye), corneal disease (a variety of conditions that affect the cornea, the small transparent part of the eye that covers the pupil and iris), and optic nerve disease (conditions that affect the nerve connecting the eye to the brain, making vision possible).
Screening and Diagnosis
Aniridia can be diagnosed by clinical examination techniques including slit-lamp examination, iris fluorescein angiography, fundoscopy, optical coherence tomography (OCT), and high-frequency ultrasound biomicroscopy (UBM). Examination of a patient’s chromosomes (known as "karyotyping") and investigation into other family cases of aniridia can determine whether the disorder is familial or sporadic. If inherited, isolated aniridia (cases not presenting as a part of another syndrome) can also be diagnosed with molecular techniques. Deletion testing (testing the absence of a segment in the PAX6 gene) and sequence analysis (a process by which the sequence is determined for a segment of the PAX6 gene) can be used to identify mutations in or near this gene associated with isolated aniridia and help diagnose patients.
Treatment and Therapy
No specific treatments for aniridia exist. There are, however, treatments available for many of the associated complications. They include but are not limited to low-vision aids such as glasses and magnifiers; computer software elements such as text enhancers and text-to-speech programs; devices that block light such as sunglasses and contact lenses with an artificial iris; and medical and surgical treatments such as cataract extraction, transplants of corneal tissue created from stem cells, antiglaucoma medication, or drainage tube surgery.
Prevention and Outcomes
When available, both genetic counseling and preimplantation genetic diagnosis, a procedure in which embryos created with techniques are screened for genetic disease before being implanted into the woman’s uterus, may prevent the inheritance of genetic diseases by offspring. Ocular testing for offspring at risk of inheriting aniridia and surveillance of secondary conditions (such as glaucoma screening, visual assessment, monitoring for aniridic fibrosis, and renal examination for patients with WAGR syndrome) cannot prevent the disease itself but can help to avoid further complications. While secondary symptoms of aniridia such as cataract, glaucoma, and corneal and optic nerve disease develop in early adulthood, abnormalities such as malformed iris and nystagmus are typically apparent earlier, usually by six weeks of age.
Bibliography
American Association for Pediatric Ophthalmology and Strabismus. "Aniridia." AAPOS. AAPOS, Mar. 2013. Web. 17 July 2014.
Daruich, Alejandra, et al. "Cogenital Aniridia Beyond Black Eyes: From Phenotype and Novel Genetic Mechanisms to Innovative Therapeutic Approaches." Prog Retin Eye Res., July 2023, www.ncbi.nlm.nih.gov/pmc/articles/PMC11062406/. Accessed 9 Sept. 2024.
Hingorani, Melanie, and Anthony Moore. "Aniridia." GeneReviews. U of Washington, Seattle, 14 Nov. 2013. Web. 17 July 2014.
"Isolated Aniridia." National Organization for Rare Disorders, 14 Feb. 2024, rarediseases.org/rare-diseases/aniridia/. Accessed 9 Sept. 2024.
Lee, H., R. Khan, and M. O’Keefe. “Aniridia: Current Pathology and Management.” Acta Ophthalmologica 86.7 (2008): 708–15. Print.
National Human Genome Research Institute. "Learning about WAGR Syndrome." Genome.gov. National Institutes of Health, 14 May 2014. Web. 17 July 2014.
"Rare Eye Disease Leaves People without an Iris." HealthDay. HealthDay News, 1 Aug. 2013. Web. 17 July 2014.
Scriver, C. R., et al., eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill, 2007. Print.
"What Is Aniridia?" American Association for Pediatric Ophthalmology and Strabismus (AAPOS), 29 Mar. 2023, www.aapos.org/glossary/aniridia. Accessed 10 Sept. 2024.