Aniridia

Aniridia is a congenital, hereditary, bilateral, extreme form of iris hypoplasia that may be associated with other ocular defects. ^{[1, 2, 3, 4]} 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. ^[5]

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. ^[6] Since the condition has a dominant transmission, proper genetic counseling should be obtained.

Aniridia is shown in the images below.

Aniridia with a vascularized corneal opacity in a young patient.

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Centrally placed cataractous lens and aniridia in a pediatric patient.

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Clinical manifestations

See the list below:

• Aniridia alone

• Aniridia in association with systemic defects

  • Wilms tumor (20% of cases) ^{[7, 8, 9]}

  • Genitourinary abnormalities

  • Mental retardation ^[10]

• 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%)

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 ^[11]

• An identifiable chromosome deletion of the short arm of chromosome 11, including band p13 ^[12]

• 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. ^{[13, 14, 15]}

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

Aniridia has no racial predisposition.

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.

The prognosis of aniridia varies from patient to patient.

Unmonitored and untreated elevated intraocular pressure may damage vision.

Cataract may require surgery.

Progressive corneal opacification may need corneal grafting.

Thoroughly educating the patient and parents about aniridia and the associated ocular anomalies and systemic problems is mandatory.