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Genetics Home Reference: your guide to understanding genetic conditions
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Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome

(often shortened to WAGR syndrome)
Reviewed March 2013

What is WAGR syndrome?

Wilms tumor, aniridia, genitourinary anomalies, and mental retardation, more commonly known by the acronym WAGR, is a syndrome that affects the development of many body systems.

Most people with WAGR syndrome have aniridia, an absence of the colored part of the eye (the iris). This can cause reduction in the sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). Aniridia is typically the first noticeable sign of WAGR syndrome. Other eye problems may also develop, such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), and involuntary eye movements (nystagmus).

Another common feature is intellectual disability (mental retardation). Some individuals with WAGR syndrome also have psychiatric or behavioral problems including depression, anxiety, attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or a developmental disorder called autism that affects communication and social interaction.

Abnormalities of the genitalia and urinary tract (genitourinary anomalies) are seen more frequently in affected males than in affected females. The most common genitourinary anomaly in affected males is undescended testes (cryptorchidism). Females may not have functional ovaries and instead have undeveloped clumps of tissue called streak gonads. Females may also have a heart-shaped (bicornate) uterus, which makes it difficult to carry a pregnancy to term.

People with WAGR syndrome have an increased risk (estimated at 45 percent) of developing Wilms tumor, a rare form of kidney cancer. This type of cancer is most often diagnosed in children but is sometimes seen in adults.

Other signs and symptoms of WAGR syndrome can include childhood-onset obesity, inflammation of the pancreas (pancreatitis), and kidney failure. When WAGR syndrome includes childhood-onset obesity, it is often referred to as WAGRO syndrome.

How common is WAGR syndrome?

The prevalence of WAGR syndrome ranges from 1 in 500,000 to one million individuals. It is estimated that one-third of people with aniridia actually have WAGR syndrome. Approximately 7 in 1,000 cases of Wilms tumor can be attributed to WAGR syndrome.

What are the genetic changes related to WAGR syndrome?

WAGR syndrome is caused by a deletion of genetic material on the short (p) arm of chromosome 11. The size of the deletion varies among affected individuals.

The signs and symptoms of WAGR syndrome are related to the loss of multiple genes on the short arm of chromosome 11. WAGR syndrome is often described as a contiguous gene deletion syndrome because it results from the loss of several neighboring genes. The PAX6 and WT1 genes are always deleted in people with the typical signs and symptoms of this disorder. Because changes in the PAX6 gene can affect eye development, researchers think that the loss of the PAX6 gene is responsible for the characteristic eye features of WAGR syndrome. The PAX6 gene may also affect brain development. Wilms tumor and genitourinary abnormalities are often the result of mutations in the WT1 gene, so deletion of the WT1 gene is very likely the cause of these features in WAGR syndrome.

In people with WAGRO syndrome, the chromosome 11 deletion includes an additional gene, BDNF. This gene is active (expressed) in the brain and plays a role in the survival of nerve cells (neurons). The protein produced from the BDNF gene is thought to be involved in the management of eating, drinking, and body weight. Loss of the BDNF gene is likely responsible for childhood-onset obesity in people with WAGRO syndrome. People with WAGRO syndrome may be at greater risk of neurological problems such as intellectual disability and autism than those with WAGR syndrome. It is unclear whether this increased risk is due to the loss of the BDNF gene or other nearby genes.

Research is ongoing to identify additional genes deleted in people with WAGR syndrome and to determine how their loss leads to the other features of the disorder.

Related Chromosome(s)

Changes involving this chromosome are associated with Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome.

  • chromosome 11

Related Gene(s)

Changes in these genes are associated with Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome.

  • BDNF
  • PAX6
  • WT1

Can WAGR syndrome be inherited?

Most cases of WAGR syndrome are not inherited. They result from a chromosomal deletion that occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family.

Some affected individuals inherit a chromosome 11 with a deleted segment from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with WAGR syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 11, which results in an increased risk of Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability.

Where can I find information about diagnosis or management of WAGR syndrome?

These resources address the diagnosis or management of WAGR syndrome and may include treatment providers.

  • Gene Review: Aniridia (http://www.ncbi.nlm.nih.gov/books/NBK1360/)
  • Gene Review: Wilms Tumor (http://www.ncbi.nlm.nih.gov/books/NBK1294/)
  • Genetic Testing Registry: 11p partial monosomy syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0206115)
  • Genetic Testing Registry: Wilms tumor, aniridia, genitourinary anomalies, mental retardation, and obesity syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2675904)
  • MedlinePlus Encyclopedia: Undescended Testicle (http://www.nlm.nih.gov/medlineplus/ency/article/000973.htm)

You might also find information on the diagnosis or management of WAGR syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/wilms-tumor-aniridia-genitourinary-anomalies-and-mental-retardation-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/wilms-tumor-aniridia-genitourinary-anomalies-and-mental-retardation-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about WAGR syndrome?

You may find the following resources about WAGR syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for WAGR syndrome?

  • 11p deletion syndrome
  • 11p partial monosomy syndrome
  • WAGR complex
  • WAGR contiguous gene syndrome
  • Wilms tumor-aniridia-genital anomalies-retardation syndrome
  • Wilms tumor-aniridia-genitourinary anomalies-MR syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about WAGR syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding WAGR syndrome?

ADHD ; anxiety ; attention deficit hyperactivity disorder ; autism ; cancer ; chromosome ; contiguous ; contiguous gene deletion syndrome ; contiguous gene syndrome ; cryptorchidism ; deletion ; depression ; expressed ; gene ; gene deletion ; genitalia ; glaucoma ; hyperactivity ; inflammation ; involuntary ; kidney ; mental retardation ; monosomy ; nephroblastoma ; neurological ; nystagmus ; obsessive-compulsive disorder ; OCD ; pancreas ; pancreatitis ; photophobia ; prevalence ; protein ; rearrangement ; reproductive cells ; sensitivity ; sign ; sperm ; syndrome ; testes ; tissue ; translocation ; tumor ; visual acuity ; Wilms tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Breslow NE, Norris R, Norkool PA, Kang T, Beckwith JB, Perlman EJ, Ritchey ML, Green DM, Nichols KE; National Wilms Tumor Study Group. Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report from the National Wilms Tumor Study Group. J Clin Oncol. 2003 Dec 15;21(24):4579-85. (http://www.ncbi.nlm.nih.gov/pubmed/14673045?dopt=Abstract)
  • Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M. WAGR syndrome: a clinical review of 54 cases. Pediatrics. 2005 Oct;116(4):984-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16199712?dopt=Abstract)
  • Han JC, Liu QR, Jones M, Levinn RL, Menzie CM, Jefferson-George KS, Adler-Wailes DC, Sanford EL, Lacbawan FL, Uhl GR, Rennert OM, Yanovski JA. Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N Engl J Med. 2008 Aug 28;359(9):918-27. doi: 10.1056/NEJMoa0801119. Erratum in: N Engl J Med. 2008 Sep 25;359(13):1414. (http://www.ncbi.nlm.nih.gov/pubmed/18753648?dopt=Abstract)
  • Robinson DO, Howarth RJ, Williamson KA, van Heyningen V, Beal SJ, Crolla JA. Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia. Am J Med Genet A. 2008 Mar 1;146A(5):558-69. doi: 10.1002/ajmg.a.32209. (http://www.ncbi.nlm.nih.gov/pubmed/18241071?dopt=Abstract)
  • Rodríguez-López R, Pérez JM, Balsera AM, Rodríguez GG, Moreno TH, García de Cáceres M, Serrano MG, Freijo FC, Ruiz JR, Angueira FB, Pérez PM, Estévez MN, Gómez EG. The modifier effect of the BDNF gene in the phenotype of the WAGRO syndrome. Gene. 2013 Mar 10;516(2):285-90. doi: 10.1016/j.gene.2012.11.073. Epub 2012 Dec 21. (http://www.ncbi.nlm.nih.gov/pubmed/23266638?dopt=Abstract)
  • Xu S, Han JC, Morales A, Menzie CM, Williams K, Fan YS. Characterization of 11p14-p12 deletion in WAGR syndrome by array CGH for identifying genes contributing to mental retardation and autism. Cytogenet Genome Res. 2008;122(2):181-7. doi: 10.1159/000172086. Epub 2008 Dec 18. Erratum in: Cytogenet Genome Res. 2009;124(1):112. (http://www.ncbi.nlm.nih.gov/pubmed/19096215?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2013
Published: April 17, 2014