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WT1-Related Syndromes

WT1-related syndromes are a group of genetic disorders that can increase a child’s risk of developing cancer. WT1-related syndromes are caused by changes in a gene known as WT1. WT1-related syndromes are hereditary. They can be passed from parents to their children.

People with these conditions have a greater risk of developing a cancerous tumor of the kidney known as Wilms tumor.

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 malformation-Range of developmental delays (WAGR) syndrome
  • Denys-Drash syndrome
  • Frasier syndrome
  • Genitourinary anomalies and Wilms tumor without renal failure

Cancer risk with WT1-related syndromes

People with WT1-related syndromes are at higher risk of developing Wilms tumors. These tumors often appear during the first 3 to 5 years of life. The risk for developing Wilms tumors or other health problems depends on the specific syndrome that a person has.

There are differences in risk for those who were born male and those who were born female. People who were born male have 1 X chromosome and 1 Y chromosome. People who were born female have 2 X chromosomes. Genes are located on chromosomes.

WAGR syndrome

People with WAGR syndrome have a 50% (1 in 2) risk of developing Wilms tumor.

Denys-Drash syndrome

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 are genetically male also have a higher risk of developing a cancerous tumor in the reproductive organs. This tumor is called a gonadoblastoma. Because Denys-Drash syndrome is rare, the exact level of risk for gonadoblastoma is not known.

People with Denys-Drash syndrome who are genetically female are not thought to be at increased risk for gonadoblastoma.

Frasier syndrome

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 rare, the exact risk for Wilms tumor is not known.

People with Frasier syndrome who are genetically male also have a higher risk of developing a cancerous tumor in the reproductive organs, called a gonadoblastoma.

People with Frasier syndrome who are genetically female usually have normal gonads (ovaries) and usually do not develop gonadoblastomas.

Genitourinary anomalies and Wilms tumor

The exact risk for Wilms tumor with this condition is unknown. Researchers and health care professionals think the risk is higher than the general population.

Other health problems with WT1-related syndromes

People with WT1-related syndromes may have other medical issues besides a higher risk of developing tumors. These may include problems with the reproductive organs, eyes, and sometimes with behavior or development.

Some people may not have medical issues, depending on the type of WT1-related syndrome they have. WT1-related Wilms tumor can be seen in families without any of these other health problems. Not all people with a WT1-related syndrome will have all the signs listed here. These signs vary from person to person.

WAGR syndrome

People with WAGR syndrome may have 1 or more of the following health issues:

  • Missing part or all of the colored part the eye (iris). This is a condition called aniridia, and it 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).
  • Issues in the reproductive organs and urinary system.
    • These issues are mostly seen in boys who can have undescended testicles. This happens when the testicles do not move down into the scrotum. Or they can have a condition known as hypospadias when 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 kidney (renal) disease. Kidney failure may develop over time. This is generally worse in patients who have been treated for a Wilms tumor.
  • Cognitive and learning disabilities. Most people with WAGR syndrome show some degree of cognitive delay and learning abilities. But the severity of this delay varies by person.
  • Behavior problems, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, anxiety, depression, and obsessive-compulsive disorder.

Denys-Drash syndrome and Frasier syndrome

The physical issues in people with Denys-Drash syndrome or Frasier syndrome are often similar. People with these syndromes may develop:

  • Issues in the reproductive organs and urinary system. These are mostly seen in those who are genetically 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 kidney disease. Kidney failure may develop over time. This is generally worse in patients who have been treated for a Wilms tumor.

Genitourinary anomalies and Wilms tumor

Boys with this condition may have issues in the reproductive organs and urinary system. These include hypospadias and undescended testicles.

Causes of WT1-related syndromes

WT1-related syndromes are caused by changes in the WT1 gene. Genes carry information telling cells in the body how to function. The WT1 gene helps develop the kidneys and the sex organs. The WT1 gene also helps control how and when cells grow, divide, and die. When a gene change causes a disorder or disease, it is called a gene mutation.

Most people without WT1-related syndromes carry 2 working copies of the WT1 gene in their cells. They receive 1 copy from their mother and 1 from their father. Cells from people with WT1-related syndromes carry 1 working copy of WT1 and 1 copy with a mutation. The type of WT1 mutation helps determine which of the WT1-related disorders a person has.

Most children with WT1-related syndromes have a new WT1 mutation that did not come from a parent. There is no history of the syndrome in their family. In these cases, the change either happened in an egg or sperm cell or in 1 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 mutation from a parent. No matter how they acquired the WT1 changes, people with WT1-related syndromes who can have children have a 50% (1 in 2) chance of passing it on with each pregnancy.

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. Researchers are looking for even more genes that might be affected in people with WAGR syndrome.

Diagnosis of WT1-related syndromes 

Health history

A health care provider may suspect that your child has WT1-related syndrome after studying their medical and family cancer history.

This information helps the health care provider and the genetic counselor know if:

  • There are more cancers than normal in your family
  • These cancers happened in people younger-than-expected ages
  • The tumors are those that are seen WT1-related syndromes
  • If the people with cancer had other physical or health features related to a WT1-related syndrome

Your provider or genetics counselor may recommend genetic testing if they suspect WT1-related syndrome. Any person who is genetically male who has both Wilms tumor and abnormal genitals (such as undescended testes or hypospadias) should be tested.

Learn more about types of genetic tests.

Genetic testing for WT1-related syndromes

A blood sample is sent to a genetic testing lab. The lab runs genetic tests that look for changes in the WT1 gene.

If your child has a WT1 mutation, a genetic counselor will work with your family to:

  • Find out if other family members should consider testing for a WT1 mutation
  • Help your family understand the increased cancer risk from WT1-related syndrome
  • Help with your decisions about prenatal genetic testing

If the care team suspects WAGR syndrome, they may do genetic tests called chromosome studies. These tests look for large areas of genetic change that may affect several genes at once.

Genetic testing before or during pregnancy

Parents may choose to do prenatal testing to find out if a pregnancy is affected by known WT1 mutations. Testing may take place either before pregnancy occurs or during pregnancy.

People considering prenatal testing should work with a prenatal genetic counselor to review the pros and cons of the testing. The genetic counselor can also help parents consider how to handle the results of the testing.

Testing before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT offers a way to test embryos for known WT1 mutations before placing them into the uterus.

Testing during pregnancy can be used to see if a pregnancy is affected with known WT1 mutations. A doctor gathers cells from the pregnancy in 1 of 2 ways:

  • Chorionic villus sampling (CVS) is done during the first 3 months of pregnancy (1st trimester).
  • Amniocentesis is done after the first 3 months of pregnancy (2nd trimester or later).

After tissue collection, the lab checks the sample for the WT1 mutation.

Both tests carry minor risks. Discuss these risks with an experienced health care provider or a genetic counselor.

Special concerns for genetic testing

Take time to think carefully about the benefits and risks of genetic testing. Speak with a genetic counselor before testing. If you decide to get tested, talk with your health care provider or a genetic counselor about your results so you can understand what they mean.

It is normal to feel sad, anxious, or angry after a diagnosis of a WT1-related syndrome. Parents who pass on a WT1-related mutations to 1 or more of their children can feel guilty. Some people with WT1 mutations could have trouble getting disability coverage, life insurance or long-term care insurance in some states.

More information about genetic discrimination can be found at

Monitoring and follow-up care for WT1-related syndromes

Screening for Wilms tumor

Wilms tumor can often be cured with proper treatment. Children with WT1-related syndromes need regular screenings to detect possible Wilms tumor as early as possible. The goal of screening is to find and treat tumors early to allow the best outcome.

Recommended screenings for children with WT1-related syndromes include:

  • Regular physical exams by a health care provider who is familiar with WT1-related syndromes.
  • Ultrasound exams of the kidneys to screen for Wilms tumor. These should be started at diagnosis, repeated every 3 months and stopped at age 8. If a provider suspects a tumor, more detailed images should be taken using CT or MRI scans. The child should be seen by a pediatric cancer specialist (pediatric oncologist).
  • Yearly check-ups with the child’s regular pediatrician.
  • Evaluation for undescended testicles and appropriate treatment for people who are genetically male and either Denys-Drash or Frasier syndrome.

Recommended screenings may change over time as health care providers learn more about WT1-related syndromes.

Care teams who manage WT1-related syndromes

Many physical issues can develop in people with WT1-related syndromes. For this reason, children need a care team with different specialists. These may include:

  • Pediatric nephrologist: Manages kidney problems
  • Pediatric oncologist: Diagnoses and treats Wilms tumor and gonadoblastoma (tumors of the gonads)
  • Pediatric surgeon and/or urologist:
    • Manages Wilms tumor
    • Surgically removes abnormal gonads to prevent gonadoblastoma, if needed
    • Can lower the testes out of the abdomen
    • Can correct other reproductive and urinary system problems
  • Pediatric endocrinologist: Evaluates and manages disorders of sex organ development
  • Genetics professional: Provides genetic counseling and genetic testing
  • Neurologist and/or developmental pediatrician: Evaluates learning delay and behavior problems
  • Ophthalmologist: Manages eye problems

Living with a WT1-related syndrome

People of any age with WT1-related syndromes have a higher risk of cancer. They should watch their health and adopt healthy habits throughout life. It is important to continue to have regular physical checkups and screenings. That way, care teams can find cancer early at the most treatable stage.

Problems to watch for

People with WT1-related syndromes should watch closely for general signs or symptoms that could signal that a Wilms tumor has developed:

  • Swelling or a hard lump in the abdomen (belly)
  • Fever
  • Nausea
  • Loss of appetite
  • Shortness of breath
  • Constipation
  • Blood in the urine

It is important to seek medical help if anything unusual appears.

Maintain a healthy lifestyle

Habits that will help you maintain a healthy lifestyle include:

  • Eat a healthy diet with lots of fruit and vegetables.
  • Get regular exercise.
  • Avoid excess sun exposure. Always wear a hat, protective clothing, and sunscreen (SPF 30 or higher) when out in the sun.
  • Avoid smoking or the use of tobacco products.
  • Avoid being around secondhand smoke.
  • Avoid excessive alcohol use.

WT1-related syndrome care at St. Jude

The St. Jude Cancer Predisposition Program is dedicated to diagnosing and screening children with a genetic predisposition for cancer. Our program offers the best clinical care possible. We engage in cutting-edge research to gain more information about genetic disorders and cancer, and to improve the care and treatment for patients who are affected by these conditions. Learn more about the Division of Cancer Predisposition at St. Jude.

Our genetic counselors, clinicians, genetics nurse practitioners, and research assistants work together to provide patients with:

  • A complete health history
  • A record of cancer that happened over the past 3 generations (family tree or pedigree) to see how diseases were passed down
  • Physical exams to check for genetic disease
  • Confidential genetic counseling and testing
  • Cancer screenings for those with genetic disease to detect and treat cancer as soon as it occurs
  • Recommended cancer treatments and ways to reduce cancer risk
  • Genetic testing for immediate (1st degree) relatives

WT1-related syndromes increase your child’s risk for cancer.

Related clinical trials

St. Jude offers clinical trials and cancer research studies for children, teens, and young adults who have cancers associated with WT1-related syndromes.

Learn more about clinical research at St. Jude.

GENETX: Assessing Gene Therapy Communication Needs

Study goal:

To learn more about participants beliefs, attitudes, and questions about gene therapy to help make web-based resources to share information. This could help patients make treatment decisions.


18 to 35 years old with rare genetic diseases

Published results
G4K: Genomes for Kids

Study goal:

The main goal of this study is to learn more about the reasons childhood tumors form and how to treat them better.

TBANK: Collecting, Banking, and Distributing Human Tissue Samples in St. Jude Biorepository

Study goal:

To provide a high-quality repository of tumor and normal samples to facilitate translational research performed by St Jude faculty and their collaborators

PG4KDS: Clinical Implementation of Pharmacogenetics

Study goal:

1) Test each patient for hundreds of gene variations that might be important for drug use. All of the gene test results will be in the research laboratory, but as time goes on, the study will evaluate scientific evidence and selectively move test results for a few genes into the medical record if the evidence strongly shows that the result can help in better prescribing of drugs for patients; 2) Estimate how often pharmacogenetic test results are moved from research tests into a patient’s medical record; 3) Use methods to choose which of these tests should be put in the medical record; 4) Use computer-based tools in the electronic medical record to help doctors use gene test results when prescribing drugs; 5) Share feelings and concerns of patients and their families about gene test information being put in their medical record.

SJFAMILY: Study of Cancer in Families

Study goal:

The main purpose of this trial is to learn about the genetic causes of cancer. 


Younger than 50 years old

A statue of children running and holding hands

Seeking treatment at St. Jude

Patients accepted to St. Jude must have a disease we treat and must be referred by a physician or other qualified medical professional. We accept most patients based on their ability to enroll in an open clinical trial.

How to seek treatment

Contact the Physician / Patient Referral Office

Call: 1-888-226-4343 (toll-free) or 901-595-4055 (local)  | Fax: 901-595-4011 | Email: | 24-hour pager: 1-800-349-4334


Learn more

If you have questions about the Genetic Predisposition Clinic and care for WT1-related syndromes, email our team at

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