rome.
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.
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.
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.
- 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
- Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome
- Atlas of Genetics and Cytogenetics in Oncology and Haematology: WAGR syndrome
- Boston Children's Hospital: Wilms Tumor in Children
- Centers for Disease Control and Prevention: Intellectual Disability (PDF)
- Cincinnati Children's Hospital: Wilms Tumor
- Great Ormond Street Hospital for Children (UK): Kidney Failure
- MalaCards: wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome
- March of Dimes: Chromosomal Conditions
- Merck Manual Consumer Version: Wilms' Tumor
- My46 Trait Profile
- Orphanet: WAGR syndrome
- Swedish Information Center for Rare Diseases
- Aniridia Foundation International
- Chromosome Disorder Outreach
- International WAGR Syndrome Association
- Kidney Cancer Association
- National Organization for Rare Disorders (NORD)
- Unique: Rare Chromosome Disorder Support Group (UK)
- University of Kansas Medical Center Resou