Aniridia in the Newborn Clinical Presentation

Updated: Apr 06, 2017
  • Author: Sophie Bakri, MD; Chief Editor: Donny W Suh, MD, FAAP  more...
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Presentation

History

An infant may come to medical attention with nystagmus or photophobia. Patients may present with strabismus and amblyopia. The family may notice an abnormal pupil, or they may describe a fixed, dilated pupil.

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Physical

Visual acuity is reduced, usually to around the 20/100 level. Pendular nystagmus, strabismus, and amblyopia may be present. Nystagmus occurs in 85-92% of patients. Ocular examination reveals absence of the irides or dilated unresponsive pupils. Other findings may include small anterior polar cataracts, pupillary membrane remnants, ectopia lentis (in 18-35%), corneal pannus, progressive keratopathy, and optic nerve or foveal hypoplasia.

Poor vision in infancy often is due to foveal or optic nerve hypoplasia and secondary nystagmus. Acquired vision loss may be due to cataract (present in 85% of cases), glaucoma (present in 70%), keratopathy, or amblyopia.

Some have considered aniridia a misnomer because a rudimentary stump of tissue usually can be found behind the limbal sclera by gonioscopy. The diagnosis can be very difficult to make in patients with a substantial amount of iris tissue. However, characteristic absence of the pupillary rim, iris sphincter muscle, and central iris tissue is noted.

Syndromes associated with aniridia

Miller syndrome (WAGR complex, 11p- syndrome)

Approximately 30% of patients with sporadic aniridia develop Wilms tumor, usually before age 5 years. The association between aniridia and Wilms tumor is referred to as Miller syndrome, after his 1964 report of 6 cases of aniridia among 440 cases of Wilms tumor. It was reported that 1.4% of patients with Wilms tumor have aniridia compared to 1 in 64,000 to 1 in 100,000 of the general population.

Affected children have other genitourinary abnormalities, craniofacial dysmorphism, hemihypertrophy, and severe mental retardation. They also may have poorly lobulated low-set ears, prominent noses, and long narrow facies. The acronym WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) describes some of the features of Miller syndrome.

Miller syndrome has been attributed to a deletion of band 11p13. Patients with sporadic aniridia should undergo a thorough physical examination and workup by a family practitioner or pediatrician.

Gillespie syndrome

Gillespie syndrome is the association of aniridia, cerebellar ataxia, and mental retardation. It is autosomal recessive, occurring in approximately 2% of patients with aniridia. These patients have anatomical defects in the cerebellum and other parts of the brain, and they are not predisposed to developing Wilms tumor.

A study of the PAX6 gene in Gillespie syndrome failed to find a mutation, suggesting that abnormalities in the PAX6 gene are not responsible for this syndrome.

Glaucoma

Glaucoma is one of the major causes of visual loss in patients with aniridia, with a reported incidence of 6-75%. This variation is explained by the referral patterns of the various institutions, the variable phenotypic expression of aniridia, and the definitions of glaucoma. Glaucoma in aniridia is rare in infants and newborns and typically is acquired in early adulthood. As a result of its delayed onset, the clinical findings of megalocornea, buphthalmos, and Haab striae typically are not found.

Progressive apposition of the rudimentary stump of iris to the trabecular meshwork is believed to occur during the first 2 decades of life. In patients without glaucoma, the structures of the anterior chamber angle appear normal by gonioscopy. In older patients with aniridic glaucoma, the severity of the glaucoma is related to the proportion of the filtration angle covered by the iris stump. The periphery of the hypoplastic stump of iris may insert anteriorly, and even where it is more open, the scleral spur and ciliary body band may be defined poorly. In the rare cases of infants with aniridic glaucoma, filtration-angle defects are present at birth. In these cases, the angle usually is covered by vascularized sheets extending from the iris, rather than being blocked by the iris stump.

Cataracts

Cataracts occur in 50-85% of patients with aniridia, usually acquired during the first 2 decades of life. At birth, small lens opacities may be noted, but these typically are not visually significant. Types of cataracts described include anterior polar, pyramidal, nuclear, lamellar, and cortical.

Visually significant cataracts in neonates require prompt surgical extraction to prevent amblyopia. However, in patients whose cataracts develop later, the factor most strongly limiting visual acuity is the presence of foveal hypoplasia, not the cataract. Areas of clear space may be present in the cataractous lens, which allows for relatively good vision. In these patients, surgery is best delayed, since the risks of glaucoma developing or progressing in aniridic eyes outweighs the small potential for visual improvement.

Ectopia lentis

Some investigators have reported lens subluxations in as many as 56% of eyes with aniridia, while others have reported none. This finding may be due to failure to detect mild cases. The zonules are believed to be histologically normal, but their molecular structure is not understood clearly.

Corneal defects

Progressive corneal opacification and pannus occur in most patients, developing as early as age 2 years. Initially, fine radial vessels invade the superficial layers of the peripheral cornea at the 6- and 12-o'clock positions and, then, involve the whole circumference. This process may progress to involve the entire cornea, requiring corneal transplantation.

Pathologically, the pannus seen in aniridic keratopathy is quite unusual; the corneal epithelium may harbor ectopic conjunctival goblet cells, and inflammatory cells are usually present. The pathogenesis is uncertain, but many theories have been proposed. It has been attributed to a total absence of the limbal girdles of Vogt and corneal epithelial limbal stem cells. PAX6 has been found in corneal and conjunctival epithelia, and it is believed that this gene may play a role in the activity of corneal stem cells.

Microcornea also has been found in most cases of aniridia.

Optic nerve and foveal hypoplasia

Posterior segment abnormalities include both macular and optic nerve hypoplasia. Approximately 75% of patients with aniridia have some degree of optic nerve hypoplasia. The macula and optic nerve are usually normal in patients with Gillespie syndrome. Mild cases may be difficult to detect because of nystagmus and corneal or lens opacities. Poor macular or retinal development may be responsible for the optic nerve hypoplasia. Because the retina is derived from neuroectoderm, as are the iris epithelium and musculature, foveal hypoplasia often is associated with aniridia.

Decreased vision and nystagmus in patients with aniridia result from faulty development of the macula, not the iris. There appears to be no correlation between the degree of iris hypoplasia and foveal hypoplasia. In some patients, foveal hypoplasia may be so subtle that fluorescein angiography may be necessary to demonstrate lack of the foveal avascular zone.

Strabismus

This is a common finding in patients with aniridia, and esotropia most frequently is found. A full cycloplegic refraction is warranted because amblyopia may occur from anisometropia or strabismus.

Nystagmus

This is commonly pendular secondary to poor vision from foveal hypoplasia. It may improve with visual maturation.

Other findings

Peripheral retinal lipoidal deposits have been reported in at least 3 patients.

Electroretinogram (ERG) amplitudes are low in patients with worse than 20/60 vision, while patients with better vision may have high a:b wave ratios.

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Causes

Aniridia may be familial or sporadic. It is caused by a mutation in the PAX6 gene on chromosome 11.

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