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 a part of the rare WAGR (Wilms' Tumor Aniridia Genitourinary Abnormalities and Mental Retardation) Syndrome. Infants with aniridia need to be carefully monitored. 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.
Isolated Aniridia is generally inherited in an autosomal dominant manner with almost complete penetrance and variable expressivity. In a third of the cases, however, it may occur sporadically. In a majority of 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. Common features observed in the three families included absence of iris tissue, corneal pannus with different degrees of severity, and foveal hypoplasia with severely reduced visual acuity. In Families 2 and 3, additional findings, such as lens dislocation, lens opacities or polar cataract, and glaucoma, were observed. Abouzeid et al. (2009) were able to identify two novel (c.170-174delTGGGC [p.L57fs17] and c.475delC [p.R159fs47]) and one known (c.718C>T [p.R240X]) PAX6 mutations in the affected members of the three families. Systemic and neurological examination was normal in all 10 affected patients. Cerebral magnetic resonance imaging showed absence of the pineal gland in all three index patients. Severe hypoplasia of the brain anterior commissure was associated with the p.L57fs17 mutation, absence of the posterior commissure with p.R159fs47, and optic chiasma atrophy and almost complete agenesis of the corpus callosum with p.R240X.
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].
Jastaneiah & Al-Rajhi (2005) conducted a study among 20 patients (36 eyes) with congenital aniridia to evaluate the association between congenital and dry eyes, and the status of limbal stem cells. Patients were divided into three groups according to corneal severity: Stage 1A (2 eyes), stage 1B (21 eyes), and stage 2 advanced (13 eyes). No correlation was found between severity of corneal involvement and lens cataractous changes. Thirty four out of thirty six were dry eyes (94.5%), correlated with the severity of corneal involvement (P= 0.001). Only the two youngest patients who had stage 1A corneal disease were without dry eyes. In 29 eyes, tear breakup time was reduced to <5 seconds, and in 31 eyes tear meniscus level was reduced to <0.5. 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. She developed deafness in early childhood. Uncorrected visual acuity was 20/100 in the left eye (OS) and 20/125 in the right eye (OD). She had an esotropia of 85 prism diopters (PD) at near and distance. In both eyes, she had -4 abduction (OU). Slit-lamp examination by indirect ophthalmoscopy with a 20 D lens showed minimal iris root for 360 degrees in the undilated pupil OU and hypoplasia in optic nerve and and foveal nerve OU. She underwent medial rectus muscle recession to 6-mm lateral rectus muscle resection OS, 8-mm lateral rectus muscle resection OD, and 13 mm from the limbus OU. Four years later, she suffered from a decreased vision OD over a period of 4 days. Slit-lamp examination revealed inferiorly subluxated lenses OU with a mild posterior subcapsular cataract OS and a dense cataract OD. At the age of 21, her vision was 20/80 OU with her aphakic refraction of +14 OD and +13.25 - 3.00 X 090 OS.
Khan and Aldahmesh (2008) reported two unrelated Saudi Arabian families with classic familial aniridia. The first family had three affected children born to an affected father, while the second family had an affected father and eight affected children from two mothers. 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. The father in the first family had severe keratopathy in both eyes, and also had documented glaucoma. Aniridia was confirmed in both families by PAX6 gene sequencing. Later, 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). All 12 probands (4 months-25 years of age; four boys and eight girls) had lens opacity and foveal hypoplasia in addition to no grossly visible iris. Four cases were familial. All cases were products of consanguineous unions except for three, one of which was endogamous. Heterozygous PAX6 mutations (including two novel mutations) were detectable in all but two cases, both of which were sporadic. In one of these two cases, the phenotype segregated with homozygosity for a previously-reported pathogenic missense FOXC1 variant (p.P297S) when homozygosity for chromosome 11q24.2 deletion (chr11:125,001,547-125,215,177 [rs114259885; rs112291840]) was also present. In the other, no genetic or genomic abnormalities were found.
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