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 Table of Contents  
Year : 2021  |  Volume : 33  |  Issue : 2  |  Page : 201-204

A descriptive presentation of a family showing various features of aniridia and its genetic analysis

1 Department of Ophthalmology, Chacha Nehru Bal Chikitsalaya, New Delhi, India
2 Department of Anatomy and Genetics Lab, All India Institute of Medical Sciences, New Delhi, India

Date of Submission03-Jun-2020
Date of Decision23-Jun-2020
Date of Acceptance26-Jun-2020
Date of Web Publication21-Aug-2021

Correspondence Address:
Dr. Meenakshi Wadhwani
Chacha Nehru Bal Chikitsalaya, New Delhi - 110 031
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/kjo.kjo_78_20

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The abnormal neuroectodermal development due to the PAX 6 gene mutation results in aniridia, a rare disorder. We report herein a family that presented with aniridia, myopia, ptosis, glaucoma, cataract, and sensory nystagmus. This family provides a unique resource for the mutational analysis of the CRYBB1, CRYBA4, and PAX-6 gene. In addition, it is important to remember that mutations are often a part of these ocular abnormalities. Patient awareness, education, and involvement in treatment are essential to prevent amblyopia associated with the cataract and nystagmus related to aniridia.

Keywords: Aniridia, cataract, Wilms tumor

How to cite this article:
Wadhwani M, Kumar M, Dada R. A descriptive presentation of a family showing various features of aniridia and its genetic analysis. Kerala J Ophthalmol 2021;33:201-4

How to cite this URL:
Wadhwani M, Kumar M, Dada R. A descriptive presentation of a family showing various features of aniridia and its genetic analysis. Kerala J Ophthalmol [serial online] 2021 [cited 2021 Nov 30];33:201-4. Available from: http://www.kjophthal.com/text.asp?2021/33/2/201/324202

  Introduction Top

Congenital aniridia is a rare ophthalmic condition (incidence between 1:64,000 and 1:100,000) that generally affects both eyes (OU).[1] The name is derived from iris hypoplasia, the most evident manifestation, which can range from almost total to only a mild phenotype. Other manifestations include nystagmus, dry eye and keratopathy, glaucoma, lens opacities, and subluxation, along with retinal, macular and optic nerve disorders, strabismus, and poor visual acuity (VA).[1] Since visual prognosis in patients with aniridia remains poor, the understanding of its genetic basis is critical toward preparing the ground for targeted future treatment options based on specific mutations.[2],[3]

  Case Report Top

A 12-year-old boy (child 1) presented to our outpatient department with decreased vision and involuntary movements of OU since birth. There was no history of photophobia, trauma, prolonged drug intake, or any other systemic abnormalities. He was born at term, with no history of consanguinity. His mother and two older male siblings had similar complaints. His father and younger sister were apparently unaffected.

VA OU was 20/200, improving to 20/80 with pinhole. Ocular examination revealed bilateral mild-to-moderate ptosis, along with pendular nystagmus. Intraocular pressure (IOP) as recorded with Goldman Applanation Tonometer was 20 mm of Hg in the right eye (OD) and 18 mm of Hg in the left eye (OS). Anterior segment examination showed transparent corneas with normal sensations and bilateral complete aniridia [Figure 1]. Both lenses were seen to be subluxated superiorly with posterior polar cataracts with spokes. Fundus examination of OU revealed a C: D ratio 0.3:1 and 0.4:1 for the right and OS, respectively. He was advised antiglare glasses after refraction, and his best-corrected VA was 20/80 in OU with −3DS in right eye and −4DS in left eye.
Figure 1: Aniridia with superiorly subluxated lens with congenital posterior polar cataract with spokes in the index case

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Examination of the family

His 16-year-old sibling (child 2) had a VA of 20/200 OU, with no improvement with pinhole. The IOP was 28 mm of Hg and 36 mm Hg, respectively, with associated nystagmus. He had bilateral aniridia with bilateral posterior polar cataracts with the superiorly subluxated lens. The fundus examination revealed optic disc cupping of 0.6 OD and 0.8 OS, respectively. The child was started on Latanoprost eye drop at night time and advised combined trabeculectomy with lens extraction OS, followed by OD. He underwent trabeculectomy OS during the postoperative period; his IOP was 18 mm Hg in the operated eye. Without any antiglaucoma medication, bleb is well-formed, vascular, and 20 mmHg OD.

His other 14-year-old sibling (child 3), had a VA of finger counting at 2 m OU. The IOP was 22 mm of Hg and 20 mm Hg, respectively, with associated nystagmus. Anterior segment examination revealed bilateral aniridia with bilateral posterior polar cataracts, as in the index case. The fundus examination of OU revealed no abnormalities. He was also advised antiglare glasses after refraction, and his best-corrected VA was 20/120 in OU with −4.5DS in OU.

Examination of mother

The VA was OD 20/200, and OS finger counting at 3 meters. IOP in OU was 18 mm Hg. Anterior segment examination revealed bilateral aniridia with bilateral posterior polar cataracts, with no nystagmus. The fundus examination was unremarkable. Bilateral cataract surgeries with IOL implantation were planned, under guarded visual prognosis, for her, but she refused. None of them had any significant systemic abnormalities.

On genetic analysis, direct sequencing of the coding region and of the flanking intronic sequences of CRYBB1, CRYBA4, and PAX6 genes revealed four nucleotide variations [Table 1] and [Figure 2], [Figure 3].
Table 1: All nucleotide variations found in CRYBB1, CRYBA4 and PAX6 genes

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Figure 2: Genetic analysis of the PAX 6 gene, showing a positive correlation

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Figure 3: Pedigree of aniridia affected family. In the pedigree, the square symbol represents males while the circle symbol represents females. Blackened symbol denotes an affected individual. The asterisks indicate the individuals whose DNA samples were available for genetic analysis

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All the detected variations have been reported in the literature. The CRYBB1 (rs57400078) nucleotide change was found in three members of the family, whereas the other two did not harbor the same change. Two polymorphisms were detected in the CRYBA4 gene (rs5761637 and rs4276) in all the family members. PAX6 sequencing revealed one synonymous nucleotide variation (c. 764A > G) present in all the affected members of the family. Nucleotide change detected in the CRYBB1 and CRYBA4 genes were found to be nonpathogenic in silicon analysis [Table 2]. Of the total four variations observed, only a single missense mutation in the PAX6 gene (c. 764A > G or p.Gln255Arg) was identified. This nucleotide variation lies in the last codon of exon 9 in the highly conserved homeodomain and leads to change at amino acid position 255 from glutamine to arginine.
Table 2: Schematic diagram of CRYGC gene showing the site of nucleotide change

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The main differential diagnosis was WAGR syndrome this is an entity that is characterized by the presence of Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation. In our patients, the IQ level and abdominal ultrasound were normal, so WAGR syndrome was ruled out. Another differential diagnosis was Gillespie's syndrome that is characterized by cerebellar ataxia and mental retardation. We ruled out this by getting a neurological and psychiatric examination, which stated that gait and IQ were normal, respectively.

  Discussion Top

Aniridia is a complex neuroectodermal developmental disorder characterized by a variable degree of hypoplasia or the absence of iris tissue, associated with multiple other ocular changes, presenting from birth or progressively over time. Pan ocular changes occur as a result of a mutation in the PAX6 gene, which is a developmental ocular gene. These changes include alterations in corneal cytokeratin expression, cell adhesion, and stem cell deficiency. It also has a fibrotic nature, which may fail filtration surgery. However, there are few reported cases with no identified mutation of PAX6.[4],[5]

Classic aniridia presents a Mendelian inheritance pattern and is an autosomal dominant disease, due to loss of function of one of the copies of the PAX6 gene. It is detectable in 90% of the cases, resulting from genetic mutations in 2/3 and from chromosomal rearrangements in 1/3).[5],[6] It codifies a regulator protein essential for the genesis of the cornea, iris, lens, drainage angle of the eye, ciliary body, and all the retinal layers. Three phenotypes have been described Autosomal dominant accounting for about 85% of cases and not associated with other systemic anomalies. Congenital sporadic seen in 13% of all aniridia and occurs in association with WAGR (Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome. Less than 2% are autosomal recessive, often associated with Gillespie's syndrome (cerebellar ataxia and mental retardation).[2],[4]

Most cases present within 6 weeks of birth, with an obvious iris abnormality or nystagmus. Affected individuals characteristically have absent or altered iris tissue and foveal hypoplasia, leading to nystagmus and impaired VA. Progressive visual failure occurs due to late-onset cataracts, glaucoma, and corneal opacification.

There is no direct correlation between genotype and phenotype, with many clinical variations. Moreover, there is also phenotypic variability between affected members of the same family. This case series highlights that PAX 6 mutations are common in aniridia. This case highlights that in case of association of aniridia with cataract or glaucoma, timely management is very important to prevent visual impairment due to amblyopia. A proper coordination between ophthalmologist and pediatrician plays an important role for the detailed ophthalmic evaluation of all family members in all cases of aniridia along with a proper systemic evaluation to rule out other associated syndromes, for example, WAGR and Gillespie syndrome in these familial aniridia cases. Furthermore, greater awareness regarding various manifestations based on severity is required as subtle variants of the disorder are often missed/misdiagnosed. Genetic testing has a very important role in confirming the investigation of PAX 6 mutation and determine if an individual is at a risk of Wilms' tumor.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Lee H, Khan R, O'keefe M. Aniridia: Current pathology and management. Acta Ophthalmol 2008;86:708-15.  Back to cited text no. 1
Nelson LB, Spaeth GL, Nowinski TS, Margo CE, Jackson L. Aniridia. A review. Surv Ophthalmol 1984;28:621-42.  Back to cited text no. 2
L´opez-Garc´ıa JS, Garc´ıa-Lozano I, Rivas L, Mart´ınez-Garchitorena J. Congenital aniridia keratopathy treatment. Arch Soc Espanola Oftalmol 2006;81:435-44.  Back to cited text no. 3
Netland PA, Scott ML, Boyle JW 4th, Lauderdale JD. Ocular and systemic findings in a survey of aniridia subjects. J AAPOS 2011;15:562-6.  Back to cited text no. 4
Traboulsi EI, Ellison J, Sears J, Maumenee IH, Avallone J, Mohney BG. Aniridia with preserved visual function: A report of four cases with no mutation ns in Pa×6. Am J Ophthalmol 2008;145:760-4.  Back to cited text no. 5
Alibés A, Nadra AD, De Masi F, Bulyk ML, Serrano L, Stricher F. Using protein design algorithms to understand the molecular basis of disease caused by protein-DNA interactions: The Pax6 example. Nucleic Acids Res 2010;38:7422-31.  Back to cited text no. 6


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2]


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