Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 19 peer-reviewed journal articles Updated
Genetics

The Genetics of Aniridia: PAX6 and Ruling Out WAGR

At a Glance

Babies born with aniridia require urgent genetic testing to check the PAX6 and WT1 genes. This testing determines if the condition is isolated aniridia or WAGR syndrome, which carries a high risk of Wilms tumor. Until WAGR is ruled out, children need kidney ultrasounds every three months.

When a child is born with aniridia, the most urgent medical priority is understanding their genetic blueprint. While aniridia primarily affects the eyes, the genes involved are part of a larger “neighborhood” on chromosome 11 [1][2]. Determining whether the genetic change is limited to the eye or involves neighboring genes is critical for your child’s overall health.

The Role of the PAX6 Gene

The PAX6 gene is the master architect for eye development. For the eyes to form correctly, the body needs two fully functional copies of this gene. Most cases of isolated aniridia are caused by haploinsufficiency—a state where only one copy of PAX6 is working [3][4].

This can happen in two main ways:

  • A “Spelling Error” (Point Mutation): A tiny change in the genetic code of the PAX6 gene makes it unreadable.
  • A “Missing Chapter” (Deletion): A piece of the chromosome is physically missing, and the PAX6 gene is part of that missing section [3][5].

How is it Inherited?

Isolated aniridia generally follows an autosomal dominant inheritance pattern. This means if one parent has the condition, there is a 50% chance of passing it to their child [6]. However, approximately 30% of cases are de novo (spontaneous) mutations, meaning they occur randomly in families with no prior history of the condition [7]. Consulting a genetic counselor can help you understand the specific risks for future pregnancies or other family members.

Isolated Aniridia vs. WAGR Syndrome

The reason doctors move so quickly after a diagnosis is to distinguish between isolated aniridia and a condition called WAGR syndrome.

WAGR is a “contiguous gene deletion syndrome.” This means a large chunk of chromosome 11 is missing, taking with it a string of neighboring genes [8][9]. The name is an acronym for the conditions it can cause:

  • Wilms Tumor: A rare form of kidney cancer.
  • Aniridia: The eye condition you have already observed.
  • Genitourinary Anomalies: Differences in the development of the urinary or genital tracts.
  • Range of Developmental Delays: Possible challenges with learning and cognitive development [1][8].

The critical difference lies in the WT1 gene, which sits right next to PAX6. If the deletion is large enough to remove both PAX6 and WT1, the child has WAGR syndrome and faces a 45% to 60% risk of developing Wilms tumor [1][10].

Essential Genetic Testing

Because you cannot tell the difference between isolated aniridia and WAGR just by looking at a baby’s eyes, comprehensive genetic testing is mandatory for all newly diagnosed infants [8][11]. Doctors use three main tools:

  1. Chromosomal Microarray: This looks for large missing pieces (deletions) across all chromosomes.
  2. MLPA (Multiplex Ligation-dependent Probe Amplification): A highly sensitive tool used specifically to see if the WT1 or PAX6 genes are missing [12][13].
  3. Next-Generation Sequencing (NGS): This “reads” the PAX6 gene letter-by-letter to find tiny spelling errors [14][15].

The Screening Guidelines

Until a deletion of the WT1 gene is definitively ruled out by genetic testing, doctors follow a strict safety protocol to protect the child’s kidneys [16][9].

  • If WAGR is confirmed (or genetic results are pending): The child must receive a renal ultrasound every 3 months [17][18]. These screenings continue until the child’s 7th birthday [19]. Early detection through these ultrasounds is highly effective, often allowing for “nephron-sparing” surgery that saves as much of the kidney as possible [1][19].
  • If WAGR is ruled out: If testing proves the WT1 gene is present and healthy, the risk of Wilms tumor drops to the same level as the general population (about 1 in 10,000) [16]. In these cases, the intense 3-month ultrasound schedule is typically no longer necessary.

Common questions in this guide

Why does a baby with aniridia need genetic testing right away?
Genetic testing is mandatory to determine if the condition is isolated aniridia or part of WAGR syndrome. Doctors must check if the WT1 gene is missing, which significantly increases the risk of a rare childhood kidney cancer called Wilms tumor.
How is isolated aniridia inherited?
Isolated aniridia usually follows an autosomal dominant pattern, meaning a parent with the condition has a 50% chance of passing it on. However, about 30% of cases are spontaneous new mutations that happen randomly in families with no history of the condition.
What screenings are needed if we don't have genetic results yet?
While waiting for genetic test results to definitively rule out a WT1 gene deletion, doctors follow a strict safety protocol. Your child should receive a renal ultrasound every three months to monitor their kidneys for any signs of Wilms tumor.
Can we stop the kidney ultrasounds if the WT1 gene is normal?
Yes. If comprehensive genetic testing proves the WT1 gene is present and completely healthy, your child's risk of Wilms tumor drops to the same level as the general population. The intensive 3-month ultrasound schedule is typically no longer required.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my child's genetic test look for both 'spelling errors' (point mutations) and 'missing pieces' (deletions) on chromosome 11?
  2. 2.Has the lab confirmed that the WT1 gene is present and completely unaffected?
  3. 3.If we haven't received definitive genetic results yet, when is my child's next renal ultrasound scheduled?
  4. 4.Does our genetic report specify if this is a 'de novo' mutation or if it was inherited?
  5. 5.If my child has a PAX6 mutation but the WT1 gene is intact, do we still need to follow the Wilms tumor screening protocol?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (19)
  1. 1

    Clinical characteristics and outcomes of children with WAGR syndrome and Wilms tumor and/or nephroblastomatosis: The 30-year SIOP-RTSG experience.

    Hol JA, Jongmans MCJ, Sudour-Bonnange H, et al.

    Cancer 2021; (127(4)):628-638 doi:10.1002/cncr.33304.

    PMID: 33146894
  2. 2

    A Chromosomal Microarray Detects Microdeletion at Chromosome Locus 11p14.3-p12 Leading to Wilms Tumor, Aniridia, Genitourinary Anomalies, and Mental Retardation (WAGR) Syndrome.

    Majjigudda RA, Menon P, Gupte S, et al.

    Cureus 2024; (16(10)):e72479 doi:10.7759/cureus.72479.

    PMID: 39600756
  3. 3

    Mutation spectrum of PAX6 and clinical findings in 95 Chinese patients with aniridia.

    You B, Zhang X, Xu K, et al.

    Molecular vision 2020; (26()):226-234.

    PMID: 32214788
  4. 4

    Genetics and epidemiology of aniridia: Updated guidelines for genetic study.

    Blanco-Kelly F, Tarilonte M, Villamar M, et al.

    Archivos de la Sociedad Espanola de Oftalmologia 2021; doi:10.1016/j.oftal.2021.02.002.

    PMID: 34243981
  5. 5

    Implication of non-coding PAX6 mutations in aniridia.

    Plaisancié J, Tarilonte M, Ramos P, et al.

    Human genetics 2018; (137(10)):831-846 doi:10.1007/s00439-018-1940-x.

    PMID: 30291432
  6. 6

    [Glaucoma in PAX6-related congenital aniridia: A review of the literature].

    Bastelica P, Daruich A, Paganelli B, et al.

    Journal francais d'ophtalmologie 2025; (48(1)):104300 doi:10.1016/j.jfo.2024.104300.

    PMID: 39368260
  7. 7

    [Congenital aniridia in children].

    Bremond-Gignac D

    La Revue du praticien 2019; (69(1)):67-70.

    PMID: 30983291
  8. 8

    Complex Chromosomal Rearrangement Involving Chromosomes 10 and 11, Accompanied by Two Adjacent 11p14.1p13 and 11p13p12 Deletions, Identified in a Patient with WAGR Syndrome.

    Marakhonov AV, Vasilyeva TA, Minzhenkova ME, et al.

    International journal of molecular sciences 2023; (24(23)) doi:10.3390/ijms242316923.

    PMID: 38069245
  9. 9

    Bilateral aniridia and congenital ureteral valve: Role of genetic testing.

    Shields LBE, Peppas DS, Rosenberg E

    Molecular genetics & genomic medicine 2020; (8(4)):e1183 doi:10.1002/mgg3.1183.

    PMID: 32056389
  10. 10

    LMO2 gene deletions significantly worsen the prognosis of Wilms' tumor development in patients with WAGR syndrome.

    Marakhonov AV, Vasilyeva TA, Voskresenskaya AA, et al.

    Human molecular genetics 2019; (28(19)):3323-3326 doi:10.1093/hmg/ddz168.

    PMID: 31304537
  11. 11

    Genetic analysis using next-generation sequencing and multiplex ligation probe amplification in Chinese aniridia patients.

    Wang L, Xu Q, Wang W, et al.

    Orphanet journal of rare diseases 2024; (19(1)):394 doi:10.1186/s13023-024-03388-3.

    PMID: 39449022
  12. 12

    Detection of BRCA1/2 large genomic rearrangements in breast and ovarian cancer patients: an overview of the current methods.

    Concolino P, Capoluongo E

    Expert review of molecular diagnostics 2019; (19(9)):795-802 doi:10.1080/14737159.2019.1657011.

    PMID: 31429350
  13. 13

    Case report: Compound heterozygosity in PKLR gene with a large exon deletion and a novel rare p.Gly536Asp variant as a cause of severe pyruvate kinase deficiency.

    Kim M, Lee SY, Kim N, et al.

    Frontiers in pediatrics 2022; (10()):1022980 doi:10.3389/fped.2022.1022980.

    PMID: 36533240
  14. 14

    Clinical Validation of Copy Number Variant Detection from Targeted Next-Generation Sequencing Panels.

    Kerkhof J, Schenkel LC, Reilly J, et al.

    The Journal of molecular diagnostics : JMD 2017; (19(6)):905-920 doi:10.1016/j.jmoldx.2017.07.004.

    PMID: 28818680
  15. 15

    Clinical Next-Generation Sequencing Pipeline Outperforms a Combined Approach Using Sanger Sequencing and Multiplex Ligation-Dependent Probe Amplification in Targeted Gene Panel Analysis.

    Schenkel LC, Kerkhof J, Stuart A, et al.

    The Journal of molecular diagnostics : JMD 2016; (18(5)):657-667 doi:10.1016/j.jmoldx.2016.04.002.

    PMID: 27376475
  16. 16

    A rare case of an isolated PAX6 mutation, aniridia, and Wilms tumor.

    Lind KT, Cost NG, Zegar K, et al.

    Ophthalmic genetics 2021; (42(2)):216-217 doi:10.1080/13816810.2020.1852577.

    PMID: 33300417
  17. 17

    Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma.

    Kalish JM, Doros L, Helman LJ, et al.

    Clinical cancer research : an official journal of the American Association for Cancer Research 2017; (23(13)):e115-e122 doi:10.1158/1078-0432.CCR-17-0710.

    PMID: 28674120
  18. 18

    Syndromic Wilms tumor: a review of predisposing conditions, surveillance and treatment.

    Liu EK, Suson KD

    Translational andrology and urology 2020; (9(5)):2370-2381 doi:10.21037/tau.2020.03.27.

    PMID: 33209710
  19. 19

    [Tumor predisposition syndromes and nephroblastoma : Early diagnosis with imaging].

    Welter N, Furtwängler R, Schneider G, et al.

    Radiologie (Heidelberg, Germany) 2022; (62(12)):1033-1042 doi:10.1007/s00117-022-01056-w.

    PMID: 36008692

This page provides educational information about aniridia genetics and WAGR syndrome screening. It does not replace professional medical advice; always consult your pediatric geneticist or ophthalmologist for your child's specific care and testing schedule.

Get notified when new evidence is published on Isolated aniridia.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.