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Aniridia
This condition often affects both eyes, leading to significant visual impairment due to issues like light sensitivity, nystagmus, and other eye complications. It is present from birth and affects individuals across all demographics.
Overview
Aniridia is a rare genetic disorder that primarily affects the eyes. It is characterised by the incomplete formation or absence of the iris, which is the coloured part of the eye responsible for controlling how much light enters. Despite its name, which means 'without iris', affected individuals often have a small rim of iris tissue visible upon careful examination [PMID:2407759]. This condition typically affects both eyes from birth and can lead to a range of visual challenges. Aniridia can also be associated with other non-ocular, or systemic, health issues in some cases.
Symptoms & clinical features
Individuals with aniridia generally experience several key symptoms linked to the absence or underdevelopment of the iris. A common symptom is photophobia, which is extreme sensitivity to light, as the iris cannot properly regulate light entering the eye. Nystagmus, an involuntary back-and-forth movement of the eyes, is also frequently observed and can reduce visual acuity [PMID:22095908]. Reduced vision, ranging from moderate to severe, is typical. Other common ocular issues include glaucoma (increased pressure within the eye), cataracts (clouding of the eye's natural lens), and corneal complications, which can further impact sight. Some individuals may also experience strabismus (crossed eyes) or ptosis (drooping eyelids).
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Affected organs
The primary organs affected by aniridia are the eyes. Specifically, the iris, retina, cornea, lens, and optic nerve can all show developmental abnormalities. The incomplete development of the iris is the most defining feature. However, the condition can also affect other parts of the eye's structure and function. In some instances, aniridia can be part of a broader syndrome, such as WAGR syndrome, which includes Wilms tumour (a kidney cancer), genitourinary anomalies, and intellectual disability [PMID:2407759]. In such cases, other organs like the kidneys and reproductive system may also be affected.
Risks & severity
The severity of aniridia can vary significantly among individuals, even within the same family. Visual impairment is typically present, ranging from mild to profound, and often worsens over time due to progressive eye complications like glaucoma and corneal degeneration. Glaucoma can develop in up to 75% of individuals with aniridia, and cataracts are also very common, affecting between 50% and 85% of cases [PMID:22095908]. These complications often require ongoing management. Aniridia is present from birth, and vision problems are usually evident in early infancy. When aniridia is part of WAGR syndrome, there is an increased risk of developing Wilms tumour, typically during childhood.
Genetic causes
Aniridia is most commonly caused by pathogenic variants in the PAX6 gene. The PAX6 gene provides instructions for making a protein that plays a crucial role in the development of the eyes, brain, and pancreas, particularly during embryonic development. This protein acts as a 'master control gene' for eye formation [PMID:2407759]. When there is a pathogenic variant in PAX6, the protein may not be produced correctly or may not function as it should, leading to the characteristic developmental abnormalities seen in aniridia. Around two-thirds of aniridia cases arising from PAX6 variants are inherited, while about one-third occur spontaneously (de novo). In some cases, a small deletion on chromosome 11 that removes the PAX6 gene and neighbouring genes can also cause aniridia, often as part of WAGR syndrome.
- PAX6 paired box 6
Inheritance pattern
Aniridia usually follows an autosomal dominant inheritance pattern. This means that a person only needs to inherit one copy of the altered PAX6 gene from either parent to develop the condition. If a parent has aniridia, there is a 50% chance with each pregnancy that their child will also inherit the condition. In about one-third of cases, the genetic change occurs for the first time in the affected individual, meaning neither parent has the condition; this is known as a de novo variant. Relatives of someone with aniridia may wish to seek genetic counselling to understand their own risks and options for genetic testing.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of aniridia is primarily made through a clinical eye examination, typically in infancy or early childhood, based on the characteristic appearance of the iris. Genetic testing is then used to confirm the diagnosis and identify the specific genetic cause, commonly a pathogenic variant in the PAX6 gene. For individuals suspected of having aniridia, referral to a clinical geneticist or ophthalmic genetic service is appropriate. In the UK, genetic testing for aniridia is available through the NHS Genomic Medicine Service. The relevant R-code for diagnostic testing for developmental ocular anterior segment abnormalities is R457.
Management & lifestyle
While there is currently no cure for aniridia, management focuses on treating symptoms and preventing complications to preserve vision. Regular eye examinations are crucial to monitor for issues such as glaucoma, cataracts, and corneal disease. Treatment may involve prescription glasses or contact lenses, low vision aids, and tinted lenses to help with photophobia. Surgical interventions may be necessary for cataracts or glaucoma. Individuals with aniridia should be under the care of an ophthalmologist specialising in genetic eye conditions. If there is concern about WAGR syndrome, regular screening for Wilms tumour (e.g., abdominal ultrasounds) would be recommended following NHS guidelines. Genetic counsellors can provide support and information regarding the condition and its inheritance.
UK care pathway
In the UK, individuals suspected of having aniridia can be referred to a clinical geneticist or ophthalmic genetic service through the NHS Genomic Medicine Service. Genetic testing, typically for PAX6 variants, is available via specific R-codes for ocular conditions. Genetic counsellors play a vital role in explaining the genetic basis of aniridia, discussing inheritance patterns, and providing support for affected individuals and their families. They can also help coordinate screening for associated conditions like WAGR syndrome when applicable.
Frequently asked questions
Is aniridia always obvious at birth?
Yes, aniridia is a congenital condition, meaning it is present from birth. The incomplete development of the iris is typically noticeable in infancy, causing symptoms like light sensitivity and involuntary eye movements.
Can people with aniridia see?
Most people with aniridia experience some degree of visual impairment, ranging from moderate to severe. While they can generally see, their vision may be reduced due to the iris malformation and associated complications like glaucoma and cataracts.
Is aniridia linked to other health problems?
In some cases, particularly when a larger genetic change is involved, aniridia can be part of a broader condition called WAGR syndrome. This syndrome also involves an increased risk of Wilms tumour, genitourinary problems, and developmental delays. Not all individuals with aniridia will have WAGR syndrome.
What support is available for individuals with aniridia in the UK?
In the UK, individuals with aniridia can access support through the NHS, including specialist ophthalmology services, low vision clinics, and genetic counselling. Patient support groups also offer valuable resources and community for affected individuals and their families.
What is the chance of passing aniridia on to my children?
If aniridia is caused by a variant in the PAX6 gene and inherited from a parent, there is a 50% chance with each pregnancy that their child will also inherit the condition. If the condition arose spontaneously (de novo) in the affected individual, the risk to their siblings is low, but the affected individual still has a 50% chance of passing it on to their own children.
References
- Tripathy K, Salini B. Aniridia. 2023. PMID: 30844160
- Moshirfar M, Hastings J, Ronquillo Y. Aniridic Fibrosis Syndrome. 2023. PMID: 32119423
- Adam MP, Bick S, Mirzaa GM. PAX6 Aniridia Syndrome. 1993. PMID: 20301534
- Hingorani M, Hanson I, van Heyningen V. Aniridia. European journal of human genetics : EJHG. 2012. PMID: 22692063
- Abdolkarimi D, Cunha DL, Lahne M. PAX6 disease models for aniridia. Indian journal of ophthalmology. 2022. PMID: 36453299
- Brauner SC, Walton DS, Chen TC. Aniridia. International ophthalmology clinics. 2008. PMID: 18427263
- Alafaleq M, Sordello L, Bremond-Gignac D. Congenital Aniridia and Ocular motility. American journal of ophthalmology. 2023. PMID: 36375586
- Casas-Llera P, Ruiz-Casas D, Alió JL. Macular involvement in congenital aniridia. Archivos de la Sociedad Espanola de Oftalmologia. 2021. PMID: 34836590