Children's Hospital Colorado

WAGR Syndrome in Children

What is WAGR syndrome?

WAGR syndrome, or WAGR complex, is a genetic disorder that affects the kidneys, urinary tract, genitalia, eyes and mental abilities. The acronym WAGR stands for Wilms tumor, aniridia, genitourinary malformations and a range of mental disabilities. Each aspect of the syndrome can affect the body in very different ways:

  • Wilms tumor, also known as nephroblastoma, is a rare malignant (cancerous) tumor that forms in the kidneys.
  • Aniridia is a disease that results in the absence of the iris (the colored part of the eye).
  • Genitourinary malformations are defects that can affect the function of the kidneys, urinary tract, scrotum, penis, testicles, clitoris and ovaries.
  • Range of mental disabilities can include both psychiatric and behavioral issues, as well as a developmental disorder called autism spectrum disorder.

What causes WAGR syndrome?

WAGR syndrome is the result of missing or inactive PAX6 and WT1 genes on chromosome 11. The PAX6 gene affects the formation of the eye, and the WT1 gene controls cell growth and suppresses tumor growth.

Because the disease is genetic, it can be inherited, or passed on, from a parent or relative.

WAGR syndrome symptoms and signs

WAGR syndrome affects many parts of the body, and the signs and symptoms can vary widely.

Aniridia

One of the most common and noticeable signs is the absence of the iris (colored part of the eye) due to aniridia. This means the eye appears to have only the black pupil surrounded by the white part of the eye (sclera). Between 80% and 99% of people with WAGR have aniridia, which can cause lower vision accuracy (visual acuity) and sensitivity to light (photophobia). Other eye complications can develop later, such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma) and involuntary eye movements (nystagmus).

Genitourinary malformations

Abnormalities of the genitalia and urinary tract (genitourinary anomalies) can also be a symptom doctors notice earlier in childhood due to trouble with urination and abnormal formation of the genitalia.

Range of mental disabilities

Mental disabilities also tend to show up earlier in a child's life, around the time many children begin to develop learning skills between the ages of 1 and 3. Parents of children with WAGR may notice difficulty processing, learning and responding to information. Some children with WAGR syndrome also show signs of psychiatric and behavioral issues such as depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or a developmental disorder called autism spectrum disorder that affects communication and social interaction.

Wilms tumor, obesity, pancreatitis or kidney failure

Later in life, a child may also experience kidney failure due to a Wilms tumor forming, which happens in about 50% of kids with WAGR syndrome.

While less common, WAGR syndrome is sometimes also associated with childhood-onset obesity, inflammation of the pancreas (pancreatitis) and kidney failure. The syndrome is often referred to as WAGRO syndrome when it includes obesity.

What tests are used to diagnose WAGR syndrome?

Your child's doctor at Children's Hospital Colorado can confirm a WAGR syndrome diagnosis through a genetic test. For the test, we will need to get a DNA sample by swabbing the inside of the cheek or by taking a blood sample.

How is WAGR syndrome treated?

WAGR syndrome treatment is determined by its symptoms.

Wilms tumor

Doctors in our Department of Pediatric Surgery and our Urologic Tumor Program are specially trained in treating Wilms tumors as well as other kidney tumors. In WAGR syndrome, we recommend having your child's kidneys checked every 3 to 4 months until about the age of 8. Using ultrasound imaging to scan the kidneys can help your child’s doctor catch a Wilms tumor early, which greatly increases the chances of being able to cure it.

We continue to monitor the kidneys for signs of nephropathy, which is a disease caused by damage to the blood vessels that help the kidneys clean the blood. About 40% of children with WAGR syndrome develop late-onset nephropathy over the age of 12.

If we detect a developing Wilms tumor, we usually start treatment with a low dosage of chemotherapy to slow the tumor’s growth. This treatment is followed by a partial nephrectomy in which we remove the affected part of the kidney, taking care to save as much of the kidney as possible.

Aniridia

Aniridia causes the absence of the iris and can lead to lowered visual acuity and photophobia. Other eye problems such as cataracts, glaucoma and nystagmus can also develop due to aniridia. Our Department of Ophthalmology has vast experience treating these conditions. Treatment can range from eye drops to medication and surgery, depending on the severity of each condition, which can vary widely.

Genitourinary malformations

We see abnormalities of the genitalia and urinary tract more frequently in boys with WAGR syndrome than in girls. The most common anomaly in boys with WAGR is undescended testicles (cryptorchidism). If a testicle can be felt within the groin, your child may undergo a surgical procedure called an orchiopexy. For the procedure, the surgeon first makes a small incision in the groin so the testicle can be located, then makes a second incision at the base of the scrotum to place the testicle to prevent it from twisting or moving upward.

Girls with WAGR syndrome can form streak gonads, which are underdeveloped ovaries that usually do not function. They can also have a heart-shaped uterus known as a bicornuate uterus, which makes it difficult to carry a pregnancy to term. Bicornuate uterus also falls under the category of a Müllerian anomaly, which our Department of Pediatric and Adolescent Genecology has extensive experience treating. Our pediatric gynecologists provide counseling for bicornuate uterus about future reproductive risks, including the risk for premature delivery, which requires additional monitoring by an obstetrician during pregnancy.

Range of mental disabilities

WAGR syndrome can lead to a range of intellectual disabilities that cause developmental delay. Psychiatric or behavioral issues can include depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD) or a developmental disorder called autism spectrum disorder that affects communication and social interaction.

Our Pediatric Mental Health Institute treats these conditions on a case-by-case basis, taking into account the combination of complications your child may have. They also work with each department to understand what medical conditions your child is facing so they can provide psychological support as your child undergoes treatment.

Why choose us for treatment of WAGR syndrome?

At Children's Colorado, we have specialists that expertly address every aspect of WAGR syndrome. From our Surgical Oncology Program to diagnose, monitor and treat WAGR syndrome-related tumors, to our ophthalmology and psychiatry departments, we work in close collaboration to care for every one of your child’s needs. Having a multidisciplinary team in one location also enables us to treat this complex condition while easing the burden on you and your child.

  • The International WAGR Syndrome Association (IWSA) is a not-for-profit organization striving to promote international knowledge and awareness of WAGR syndrome and its complications and treatments. IWSA also helps to stimulate research and reaches out to those affected by WAGR syndrome to help improve their lives.
  • The Genetic and Rare Diseases Information Center is a program of the National Center for Advancing Translational Sciences. It provides access to current, reliable and easy-to-understand information in English or Spanish about rare or genetic diseases.
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