Patients with aniridia show a bilateral nearly complete or partial absence of iris (▶ Fig. 6.1). Estimated incidence varies between 1 in 40,000 and 100,000 people. It is caused by a mutation of the transcription factor PAX6 gene, which is located on chr11p13. PAX6 is the “master control gene” for eye development. Therefore, disruption of this gene’s function results in abnormal expression of many downstream genes potentially causing abnormalities in virtually every part of the eye, including nystagmus, corneal pannus (▶ Fig. 6.2) ranging from peripheral avascular pannus due to limbal stem cell deficiency to severe pancorneal vascularization, strabismus, refractive error, glaucoma, cataract (especially anterior pyramidal; ▶ Fig. 6.3), foveal/macular hypoplasia (▶ Fig. 6.4 and ▶ Fig. 6.5) that results in varying degrees of visual impairment, and optic nerve hypoplasia.


Fig. 6.1 Patient with “partial” aniridia due to PAX6 gene mutation.


Fig. 6.2 Keratopathy in a patient with aniridia.


Fig. 6.3 Anterior pyramidal cataract in a patient with aniridia.


Fig. 6.4 Macular hypoplasia in a patient with aniridia. Note the absence of foveal reflex and vessels coursing through the central macula.


Fig. 6.5 Optical coherence tomography demonstrating foveal hypoplasia in a patient with aniridia.

6.2 Molecular Genetics

Aniridia is an autosomal dominant (AD) disorder. Most PAX6 mutations (40%) are premature termination codons (nonsense). Missense mutations (25%) result in less severe forms of aniridia. Intragenic deletions may also occur and usually result in more severe disease. Some mutations in the gene will be expressed only as isolated parts of the disorder without iris malformation: AD macular hypoplasia, cataract, or keratitis. Homozygous or compound heterozygous disruption of PAX6 function results in anophthalmia, brain malformation, and often death.

If a heterozygous contiguous gene deletion occurs within the 11p13 region, encompassing PAX6 as well as the nearby WT1 gene, WAGR syndrome results, with a prevalence of 1 in 500,000. Patients with deletion of PAX6 and WT1 have a 45 to 50% risk of developing Wilms’ tumor. These deletions vary in size from those large enough to be detected by karyotype to submicroscopic deletions requiring FISH (fluorescence in situ hybridization) or chromosomal microarray to detect. Even smaller deletions may not encompass WT1 but still result in the other manifestations. Deletions may occur de novo or as a result of parental translocations. Very small deletions can rarely result in a history of familial aniridia with minimal associated systemic manifestations.

6.2.1 Differential Diagnosis

Axenfeld–Rieger spectrum (OMIM 180500)

Axenfeld–Rieger spectrum (OMIM 180500) may be distinguished from aniridia by the presence of posterior embryotoxon and the absence of corneal vascularization or foveal hypoplasia. Rarely, an aniridic variant may occur due to deletion or duplication of 6p25, but these patients also have posterior embryotoxon and normal foveae.

Iris coloboma.

Iris coloboma is often accompanied by posterior coloboma. It may be unilateral. In the absence of fundus coloboma, there is no macular hypoplasia. Cornea is normal.

Albinism (OMIM 203100)

Albinism typically presents in early infancy with nystagmus but a structurally complete iris and the presence of iris transillumination, fundus hypopigmentation, gray optic nerve, and, in the case of oculocutaneous albinism, skin and hair hypopigmentation. In addition, a three-lead VEP (visual evoked potential) may show pattern reversal in albinism patients. Iris transillumination does not occur in aniridia.

Peters anomaly (OMIM 604229)

The most common manifestation is corneal opacification at birth with posterior corneal scalloped defect seen on optical coherence tomography (OCT) or ultrasound biomicroscopy (UBM), often with iridocorneal adhesions. Various iris anomalies may occur, but foveae are usually normal, though other posterior segment anomalies can occur. This can be unilateral.


It is usually unilateral with other findings of trauma and a positive history. It may also occur as a result of surgery.

Other anterior segment Dysgenesis

A wide variety of anterior segment dysgenesis may have aniridia variants, but these patients often have microphthalmia, other anterior segment findings atypical for aniridia, and normal foveae.

Persistent Fetal Vasculature (OMIM 221900)

It is typically unilateral, and usually associated with posterior cataract. It can be accompanied by significant retinal abnormalities. It may be seen in true aniridia as it is a developmental defect of the eye, but is usually seen in isolation or with many other anterior segment dysgenesis.

Gillespie syndrome (OMIM 206700).

This is an AR condition characterized by aniridia, mental retardation, and cerebellar ataxia. Although it has been associated with PAX6

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Apr 7, 2019 | Posted by in OPHTHALMOLOGY | Comments Off on Aniridia

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