Aniridia is a congenital ocular disorder characterized by partial or complete absence of the iris. The most obvious manifestation of the condition is iris hypoplasia. However, this can also be accompanied by many other clinical features, including corneal degeneration, cataracts, nystagmus, and foveal and optic nerve hypoplasia. Aniridia typically causes severe visual impairment.
The incidence of congenital aniridia ranges from 1:64,000 to 1:96,000. Aniridia generally occurs in isolation. Rarely, it may be accompanied by other ocular malformations or as part of the rare WAGR (Wilms' Tumor Aniridia Genitourinary Abnormalities and Mental Retardation) Syndrome. Several treatment options are available for managing the glaucoma associated with the condition. These include the use of miotics to improve the aqueous outflow, adrenergic agonists, beta blockers, or carbonic anhydrase inhibitors. Patients may require spectacles to correct refractive errors, and tinted glasses to guard against photophobia. No surgical procedure has been convincingly found to be the treatment of choice for the glaucoma associated with Aniridia.
Aniridia is generally inherited in an autosomal dominant manner with almost complete penetrance and variable expressivity. However, in a third of the cases, it may occur sporadically. In most patients with aniridia, causal mutations have been found in the PAX6 (Paired Box 6) gene, located on chromosome 11. PAX6 codes for a transcription factor that is involved in several development pathways and is expressed early in the development of the eye, numerous regions of the brain, and the pancreas. Within the brain, PAX6 is also involved in the development of the olfactory bulb.
Abouzeid et al. (2009) studied 10 patients with aniridia from three families of Egyptian origin. Two novel PAX6 mutations (c.170-174delTGGGC and c.475delC) and a previously reported one (c.718C>T) were identified in the patients.
Al Nassar et al. (1996) described a 2.5-year old female with bilateral aniridia together with some dysmorphic features. Sequencing of exon 10 of the PAX6 gene did not reveal any mutation. However, the patient was found to have a de novo balanced translocation t[6;18] [q16;q23].
(Al Nassar KE, Murthy SK, Verghese L. De novo balanced translocation t[6;18] [q16;q23] in a female with bilateral aniridia. Med Princ Pract. 1996; 5(3):163-6.)
Jastaneiah & Al-Rajhi (2005) conducted a study among 20 patients (36 eyes) with congenital aniridia to evaluate the association between congenital aniridia and dry eyes. Stenosed meibomian orifices, reduction in tear breakup time and tear meniscus levels were found in majority of the cases (77.8%, 90.7% and 88.6% of cases respectively). In addition, 8 of 23 eyes (35%) had early limbal stem cell deficiency, and 15 of 23 eyes (65%) had advanced limbal stem cell deficiency.
Khan & Aldahmesh (2006) described a 13-year-old female of normal karyotype (46, XX) suffering from bilateral Duane syndrome and bilateral aniridia. She had inward deviation of the eyes since birth and developed deafness in early childhood. Patient was reported to have no family history of strabismus or any kind of congenital abnormalities.
Khan and Aldahmesh (2008) reported two unrelated Saudi Arabian families with classic familial aniridia. Both pedigrees were consistent with an autosomal dominant or pseudodominant mode of inheritance. All affected individuals had documented low vision, pendular nystagmus, lack of iris tissue, lenticular opacity, foveal hypoplasia, and moderate corneal panus. Aniridia was confirmed in both families by PAX6 gene sequencing.
Khan et al. (2008) performed an ophthalmic evaluation on a Saudi infant girl and her first cousin consanguineous parents. The 1-month old girl presented with congenital glaucoma and aniridia. She had almost complete lack of iris tissue, along with corneal haze, clinical aniridia and glaucoma. Her mother had prominent Schwabe line, subtle iris hypoplasia, iris stands bridging the angle, increased intraocular pressure, and glaucomatous optic nerve cupping. The father had a normal ocular examination. The infant and her mother were diagnosed with congenital glaucoma and aniridia with a milder phenotype in the mother. Both were found to carry a heterozygous mutation in the FOXC1 gene. The child had two older siblings with no history of ocular or medical disease.
In a subsequent study to determine the genetic and genomic alterations underlying classic aniridia in Saudi Arabia, Khan et al. (2011) conducted a prospective study of consecutive patients referred to a pediatric ophthalmologist (2005-2009). Except for three cases, all were born to consanguineous parents. Heterozygous PAX6 mutations were identified in all but two cases, both of which were sporadic. One of these two cases had homozygous FOXC1 variant (p.P297S) and a homozygous deletion at chromosomal region 11q24.2.