Aniridia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Aniridia is an eye disorder that is characterized by a complete or partial absence of the colored part of the eye (the iris). Aniridia is typically present from birth (congenital) and affects both eyes. The pupils may also be abnormal or misshapen.

People with aniridia can have other eye problems that may be congenital or develop later in life. Clouding of the lenses of the eyes (cataracts) occurs in most people with aniridia. Affected individuals often have involuntary eye movements (nystagmus) or an increased sensitivity to light (photophobia). Underdevelopment of a specific region at the back of the eye (foveal hypoplasia) can reduce the sharpness of vision (visual acuity).

Additional signs and symptoms of aniridia may include problems with the cornea (aniridia-associated keratopathy). The cornea is the clear outer covering of the eye. Aniridia can also cause increased pressure in the eye (glaucoma) in late childhood through early adulthood. In some affected individuals, the structures that carry information from the eyes to the brain are underdeveloped (optic nerve hypoplasia). Many of these eye problems contribute to vision loss that worsens over time. The severity of symptoms is typically the same in both eyes.

In rare cases, individuals with aniridia have additional health problems, which can include behavioral issues, metabolic disorders, and problems detecting odors.

Aniridia can affect the eyes alone (isolated) or it can occur with other features as part of a syndrome. Aniridia is a common feature of certain genetic conditions including Gillespie syndrome and WAGR syndrome.

Injuries to the head or eyes can also cause aniridia. This type of aniridia is not genetic and can occur at any age.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the PAX6 gene can cause aniridia. The PAX6 gene provides instructions for making a protein that is involved in the early development of the eyes, brain and spinal cord (central nervous system), and the pancreas. The PAX6 protein belongs to a group of proteins called transcription factors. These proteins bind to specific regions of DNA and regulates the activity of other genes. After birth, the PAX6 protein is found in many different eye structures, where it regulates gene activity.

Pathogenic variants in the PAX6 gene cause cells to produce a nonfunctional PAX6 protein that is unable to bind to DNA and regulate the activity of other genes. Without enough functional PAX6 protein, the formation of the eyes is disrupted before birth, leading to the various signs and symptoms of aniridia.

In a small percentage of cases, aniridia can be caused by pathogenic variants in other genes. These genes produce proteins that control the expression of the PAX6 gene. Pathogenic variants in these genes lead to a reduction in PAX6 protein activity, much like variants in the PAX6 gene.

When aniridia is part of a syndrome, it is caused by gene variants associated with that syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Aniridia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In approximately two-thirds of cases, a person with aniridia inherits the pathogenic variant from one affected parent. The remaining one-third of cases result from a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Aniridia occurs in 1 in 40,000 to 100,000 newborns worldwide.

Which doctor should you see?

The suggested department for discussing Aniridia is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Aniridia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.