WT1-Related Syndromes are hereditary, which means they can be passed from parents to their children.
People with WT1-Related Syndromes may have other medical issues besides an increased risk of developing Wilms tumor. These may include problems with the reproductive organs, eyes, and sometimes with behavior or development. Whether someone has these medical issues depends on the type of WT1-Related Syndrome that the person has. WT1-related Wilms tumor can be seen in families without any of these other health problems.
Sometimes people with WT1-Related Syndromes have a pattern of health problems that can be grouped into one of the following syndromes:
- Wilms tumor-Aniridia-Genitourinary abnormalities-Range of developmental delays (WAGR) Syndrome
- Denys-Drash Syndrome
- Frasier Syndrome
WT1-Related Syndromes are caused by changes in a gene known as WT1. Genes carry information telling cells in the body how to work. The WT1 gene is needed to develop the kidneys and the gonads (ovaries in people with the genetic makeup of a female and testes in people with the genetic makeup of a male). Within these tissues, the WT1 gene helps control how and when cells grow, divide, and die.
Most people without WT1-Related Syndromes carry two working copies of the WT1 gene in their cells. One copy is inherited from each parent. Cells from people with WT1-Related Syndromes carry one working copy of WT1 and one copy that is changed. This change causes the gene to not work right. It is called a WT1 variant. The type of WT1 variant helps determine which of the WT1-related disorders a person has.
Most children with WT1-Related Syndromes have a new WT1 variant that did not come from a parent. These children have no history of the syndrome in their family. In these cases, the change either happened in an egg or sperm cell when the child was formed or in one of the child’s cells during pregnancy. These children are the first in their families to have a WT1-Related Syndrome. A few children with WT1-Related Syndromes inherited their WT1 variant from a parent. No matter how they acquired the WT1 changes, people with WT1-Related Syndromes who are able to have children have a 50% (or 1 in 2) chance of passing it on to their children.
In WAGR Syndrome, other genes besides WT1 are affected. These include PAX6, which affects how the eyes develop, and BDNF, which is probably involved in managing eating, drinking, and body weight. Research is ongoing to look for more genes that might be affected in people with WAGR Syndrome.
A doctor may suspect this diagnosis after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about the person’s health and the health of other family members. Read more about genetic counseling and genetic testing.
Diagnosing this syndrome is usually done by sequencing the WT1, PAX6, and/or BDNF genes to find variants (gene changes). Other tests (for example, a microarray) may be done to look for large deletions of genetic information.
People with WT1-Related Syndromes are at higher risk of developing Wilms tumors. These tumors generally appear during the first 3–5 years of life. The risk for developing Wilms tumors or for other health problems depends on the specific syndrome that a person has.
People with WAGR Syndrome have a 50% (1 in 2) risk of developing Wilms tumor.
People with Denys-Drash Syndrome have a more than 90% (9 out of 10) risk of developing Wilms tumor. People with Denys-Drash Syndrome who have the chromosomal (genetic) makeup of a male also have a higher risk of developing a cancerous tumor in the reproductive organs, called a gonadoblastoma. Because Denys-Drash Syndrome is very rare, the exact risk for gonadoblastoma is not known. People with Denys-Drash Syndrome who have the chromosomal (genetic) makeup of a female are not thought to be at increased risk for gonadoblastoma.
People with Frasier Syndrome have a slightly higher risk of developing Wilms tumor than people without a WT1-Related Syndrome, but the overall risk is still low. Because Frasier Syndrome is very rare, the exact risk for Wilms tumor is not known. People with Frasier Syndrome who have the chromosomal (genetic) makeup of a male also have a higher risk of developing a cancerous tumor in the reproductive organs, called a gonadoblastoma. People with Frasier Syndrome who have the chromosomal (genetic) makeup of a female usually have normal gonads (ovaries) and usually do not develop gonadoblastomas.
Cancer screening involves tests to check for cancer before symptoms occur. The goal is to find cancer at the earliest and most treatable stage. Guidelines for cancer screening are available online. Recommended screenings may change over time as doctors learn more about this syndrome, so these screening tests should be discussed with a health care provider who knows this syndrome well.
Other ideas to reduce the risk of cancer include:
- Eat a healthful diet with lots of fruits and vegetables
- Get regular exercise
- Avoid smoking or using tobacco products
- Avoid secondhand smoke
- Avoid excess sun exposure and always wear sunscreen, hat, and protective clothing when out in the sun
- Get medical attention for unusual or ongoing symptoms
Many medical issues can develop in people with WT1-Related Syndromes.
People with WAGR Syndrome may have one or more of these issues:
- Loss of part or all of the colored part the eye (iris), a condition called aniridia. This is seen in most people with the syndrome.
- Other eye problems, such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), and involuntary eye movements (nystagmus).
- Defects in the reproductive organs (genitals) and urinary system.
- These defects are mostly seen in boys who can have undescended testicles (the testicles fail to move down into the scrotum) or a condition known as hypospadias (the urinary opening is located on the underside of the penis instead of the tip).
- Girls with this condition usually have normal genitals. Some girls may also have a heart-shaped (bicornuate) uterus, which makes it hard to carry a pregnancy to term.
- End-stage renal (kidney) disease. Renal failure may develop over time. This issue is generally worse in people who have been treated for a Wilms tumor.
- Mental and learning disabilities. Most people with WAGR Syndrome show some degree of cognitive delay, although the severity varies from person to person.
- Behavior problems, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, anxiety, depression, and obsessive-compulsive disorder.
The medical issues in people with Denys-Drash Syndrome or Frasier Syndrome are similar. People with these syndromes may develop the following issues:
- Defects in the reproductive organs (genitals) and urinary system. These defects are mostly seen in people who have the chromosomal (genetic) makeup of a male.
- Some may have testicles that are undescended.
- Some may have genitals that do not look clearly male or clearly female. When this occurs, it is called “ambiguous genitalia.”
- Others may have genitals that appear completely female.
- End-stage renal (kidney) disease. Renal failure may develop over time. This issue is generally worse in people who have been treated for a Wilms tumor.
Because of the medical concerns related to this syndrome, specialists in the following areas may need to assess a child with WT1-Related Syndromes:
- Nephrology
- Urology
- Surgery
- Endocrinology
- Neurology
- Developmental pediatrics
- Ophthalmologist (for aniridia and other eye problems)
Resource about WT1-Related Syndromes:
- International WAGR (Wilms tumor-Aniridia-genitourinary malformation-Range of developmental delays Syndrome Association (www.wagr.org)
Resources about Wilms tumor:
- American Cancer Society – Wilms Tumor (www.cancer.org/cancer/types/wilms-tumor.html)
Other resources:
- Making Sense of Your Genes: A Guide to Genetic Counseling (www.ncbi.nlm.nih.gov/books/NBK115508/)
Adapted from educational materials developed by the St. Jude Children’s Research Hospital Cancer Predisposition Program