Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome

Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome, more commonly known by the acronym WAGR syndrome, is a condition 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 be present, 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.

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.

The prevalence of WAGR syndrome is unknown; however, it appears to be a rare condition. 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.

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. These genes play significant roles in early development. Researchers believe that loss of the PAX6 gene is associated with the characteristic eye features of WAGR syndrome and may also affect brain development. Deletion of the WT1 gene appears to be associated with Wilms tumor and the genitourinary abnormalities.

Researchers are working to identify additional genes deleted in people with WAGR syndrome and determine how their loss leads to the other features of the disorder.

Read more about the PAX6 and WT1 genes and chromosome 11.

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 for Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability characteristic of this disorder.