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Aniridia is both the name of a disease and a group of disorders. This because aniridia is both an isolated ocular disease and a feature of several malformation syndromes. Absence of the iris was first reported in the early 19th century. The hallmark of the disease is bilateral iris hypoplasia which may consist of minimal loss of iris tissue with simple radial clefts, colobomas, pseudopolycoria, and correctopia, to nearly complete absence. Goniosocopy may be required to visualize tags of iris root when no iris is visible externally. Glaucoma is frequently present (~67%) and often difficult to treat. It is responsible for blindness in a significant number of patients. About 15% of patients are diagnosed with glaucoma in each decade of life but this rises to 35% among individuals 40-49 years of age. Hypoplasia and dysplasia of the fovea are likely responsible for the poor vision in many individuals. Nystagmus is frequently present. The ciliary body may also be hypoplastic.
Visual acuity varies widely. In many families it is less than 20/60 in all members and the majority have less than 20/200. Photophobia can be incapacitating. Posterior segment OCT changes suggest that outer retinal damage suggestive of a phototoxic retinopathy may also be a factor in the reduced acuity. Cataracts (congenital in >75%), ectopia lentis (bilateral in >26%), optic nerve hypoplasia, variable degrees of corneal clouding with or without a vascularized pannus, and dysgenesis of the anterior chamber angle are frequently present.
Increased corneal thickness (>600 microns) has been found in some series and should be considered when IOP measurements are made. In early stages of the disease, focal opacities are present in the basal epithelium, associated with sub-basal nerves. Dendritic cells can infiltrate the central epithelium and normal limbal palisade architecture is absent. The tear film is often unstable.
Attempts have been made to divide aniridia into several types based upon the type and degree of ocular abnormalities but modern genotyping allows more specific determination of classification, especially when systemic features are also considered.
In addition to ‘pure’ aniridia in which no systemic features are found, at least six disorders have been reported in which systemic anomalies do occur. Three of these have associated renal anomalies, including Wilms tumor with other genitourinary anomalies and mental retardation, sometimes called WAGR (194072) syndrome, another (612469) with similar features plus obesity sometime called WAGRO (612469) syndrome reported in isolated patients, and yet another with partial aniridia (206750) and unilateral renal agenesis and psychomotor retardation reported in a single family. Aniridia with dysplastic or absent patella (106220) has been reported in a single three generation family. Cerebellar ataxia and mental retardation with motor deficits (Gillespie syndrome; 206700) has been found in other families. Another 3 generation family has been reported in which aniridia, microcornea and spontaneously resorbed cataracts occured (106230).
About one-third of patients with aniridia also have Wilms tumor and many have some cognitive deficits..
The majority of cases have a mutation in the paired box gene (PAX6) complex, or at least include this locus when chromosomal aberrations such as deletions are present in the region (11p13). This complex (containing at least 9 genes) is multifunctional and important to the tissue regulation of numerous developmental genes. PAX6 mutations, encoding a highly conserved transcription regulator, generally cause hypoplasia of the iris and foveal hypoplasia but are also important in CNS development. It has been suggested that the PAX6 gene may be the only gene defect associated with aniridia. More than 300 specific mutations, most causing premature truncation of the polypeptide, have been identified. Associated abnormalities may be due to a second mutation in the WT1 gene in WAGR (194072) syndrome, a deletion syndrome involving both WT1 and PAX6 genes at 11p13. The WAGRO syndrome (612469) is caused by a contiguous deletion in chromosome 11 (11p12-p13) involving three genes: WT1, PAX6, and BDNF. All types are likely inherited as autosomal dominant disorders although nearly one-third of cases occur sporadically.
Treatment is directed at the associated threats to vision such as glaucoma, corneal opacities, and cataracts. Glaucoma is the most serious threat to vision and difficult to treat although good results have been reported with glaucoma drainage devices. All patients should have eye examinations at appropriate intervals throughout life, focused on glaucoma screening. It is well to keep in mind that foveal maldevelopment often precludes significant improvement in acuity and heroic measures must be carefully evaluated. Specifically, corneal transplants frequently fail.
Low vision aids are often helpful. Tinted lenses can minimize photophobia. Occupational and vocational training should be considered for older individuals.
Young children with aniridia should have periodic examinations with renal imaging as recommended by a urologist.
In mice, postnatal topical ocular application of ataluren-based eyedrop formulations can reverse malformations caused by PAX6 mutations.