Introduction
Background
Aniridia is a congenital, hereditary, bilateral, extreme form of iris hypoplasia that may be associated with other ocular defects. It describes an extreme form of iris hypoplasia in which the iris appears absent on superficial clinical examination. However, gonioscopy shows the presence of the iris root. Aniridia is not just an isolated defect in iris development but is a panocular disorder with macular and optic nerve hypoplasia, cataract, and corneal changes that are other anomalies that lead to decreased vision and nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time.
Patients with aniridia usually lack a foveal reflex, indicating poor macular development. True aplasia of the optic nerve also can occur. All these patients need specialized management of each individual problem. Because of poor visual acuity and nystagmus, low vision aids are very helpful. Lifelong regular follow-up care is necessary for the early detection of any new problems, especially glaucoma, lens, and systemic problems, so that timely treatment is given. Since the condition has a dominant transmission, proper genetic counseling should be obtained.
Clinical manifestation
- Aniridia alone
- Aniridia in association with systemic defects
- Wilms tumor (20% of cases)
- Genitourinary abnormalities
- Mental retardation
- Aniridia in association with ocular defects
- Albinism
- Ectopia lentis (50%)
- Spontaneous lens dislocation
- Arcus juvenilis
- Keratoconus
- Cataract (50-85%)
- Glaucoma (30-50%)
- Nystagmus
- Strabismus
- Optic nerve hypoplasia (75%)
Pathophysiology
The pathogenesis of aniridia is attributed to a primary developmental arrest of the neuroectoderm and a secondary alteration of all 3 neural crest waves of the mesenchyme. The functional development of the anterior segment is a complex interrelationship between the neural ectoderm and the neural crest waves of the mesenchyme. The pathogenesis may involve defective formation or excessive regression of various layers of the anterior segment caused by cellular or biochemical aberrations. This explains the combined anterior and posterior segment neural ectodermal and mesenchymal defects. The iris stroma is hypoplastic, indicating an altered third neural crest wave of mesenchyme.
Aniridia occurs as the following:
- Autosomal disorder
- An identifiable chromosome deletion of the short arm of chromosome 11, including band p13
- Sporadic case
The exact defect in iris morphogenesis giving rise to aniridia is unknown. Because the iris pigment epithelium, the iris musculature, the retina, and the optic nerve are derived from neuroectoderm, there may be a common embryologic origin for these anomalies. As an isolated ocular malformation, aniridia is an autosomal dominant disorder, which is caused by a mutation in the PAX6 (paired box gene family) gene.
Patients with aniridia who have a positive family history are not at an increased risk for Wilms tumor. Two genetic loci for aniridia have been identified: one (AN1) on chromosome arm 2p and one (AN2) on chromosome 11.
Patients with aniridia without a positive family history have a 30% chance of developing Wilms tumor, and they represent new mutations for the autosomal dominant gene. About one third of such patients have a mutation that affects the WT and AN2 loci, causing the patient to develop Wilms tumor; the other two thirds of patients have a mutation of just the AN2 locus. Because of the high mortality from Wilms tumor, those patients with the WT and AN2 mutations have a low probability of reproducing, whereas those with just AN2 mutations have normal fertility and, hence, a 50% risk to pass the aniridia gene mutation to each child.
Frequency
United States
At present, aniridia strikes 1 in 60,000 individuals; in Canada, this would represent only 475 individuals based on a present population of 28.5 million. In the United States, studies have shown the incidence to be 1 in 90,000. Based on a population of 265 million, this would represent 2945 people.
International
Aniridia is rare and has an incidence of 1 per 64,000 to 1 per 96,000 live births. About two thirds of these cases are familial.
Mortality/Morbidity
All patients with aniridia are visually handicapped for a lifetime. This already reduced vision is threatened further by such complications as cataract and glaucoma. Those patients with Wilms tumor have a reduced span of life.
Race
No racial predisposition exists.
Age
- Congenital glaucoma and aniridia usually are not associated at birth. The glaucoma develops at either the preteen or the teenage level.
- Significant cataracts may occur before puberty. The risk for cataract increases with age, with lens opacities observed in 50-85% of patients during the first 2 decades of life.
Clinical
History
- The history is straightforward. The condition is discovered early in life, especially in whites. In blacks, the condition might remain undiscovered for a long time until an ophthalmologist examines the eyes for visual problems. The patient presents with the following problems:
- Absence of iris
- Nystagmus
- Strabismus
- Reduced vision
- Thorough family history
- Specific inquiry about any ocular abnormality and/or low vision
- Dental anomaly
- Protruding umbilicus
- Genitourinary abnormalities (Wilms tumor)
- Mental retardation
- Thorough systemic examination of the patient
Physical
A detailed ocular examination is sometimes difficult because of photophobia and nystagmus. If slit lamp flash pictures are taken, they can provide detailed information on corneal opacities and blood vessels, the depth of the anterior chamber, the edge of a transparent dislocated lens, the presence or absence of zonular fibers, and the presence of lenticular opacities. Photographs are useful to observe changes in the tissues with the passage of time. A picture session is especially important in children.
The patient might show the following findings:
- Nystagmus
- Strabismus
- Photophobia
- Cornea
- Pannus
- Epithelial ulcers
- Aniridic keratopathy
- Arcus juvenilis
- Microcornea
- Anterior chamber
- Best judged with a slit lamp microscope
- Configuration dependent upon the position of the crystalline lens
- Iris
- Complete absence of iris on oblique illumination
- Hypoplasia with irregular pupillary margins (atypical coloboma of pupil)
- Root of the iris visible on gonioscopy
- Angle of the anterior chamber - Trabecular meshwork may be partially or completely covered by the iris stump.
- Crystalline lens
- Transparent or opaque
- Ectopia lentis
- Completely dislocated lens
- Vitreous - Usually normal
- Fundus
- Optic nerve hypoplasia
- Macular reflex dull
- Glaucomatous cupping
- Intraocular pressure
- Normal
- Increased
- Vision - Usually about 20/200 or less
Causes
Aniridia is caused by the following:
- An identifiable chromosome deletion of the short arm of chromosome 11, including band p13.
- Patients with aniridia who have a positive family history: Two genetic loci for aniridia have been identified, one (AN1) on chromosome arm 2p and one (AN2) on chromosome 11.
- As an isolated ocular malformation, aniridia is an autosomal dominant disorder, which is caused by a mutation in the PAX6 (paired box gene family) gene.
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Further Reading
Keywords
absence of iris, partial or complete absence of iris, congenital aniridia, iridemia, iris hypoplasia, panocular disorder, cataract
