Denys-Drash syndrome is a rare genetic mutation that affects how your child’s kidneys and gonads develop. Their kidneys stop working by the time they reach the age of 3. Denys-Drash syndrome also greatly increases your child’s risk of developing a kidney tumor. Treatment usually involves dialysis and surgeries.
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Denys-Drash syndrome (DDS) is a genetic disorder that affects the kidneys and genitals. It can lead to three conditions:
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Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy
Denys-Drash syndrome is a rare but serious disease. During the first few years of life, kidney function gets worse. Eventually, the kidneys fail. When this happens, they can’t filter blood well. This leads to swelling and a buildup of waste products in the body.
Preserving kidney function for as long as possible is important. But when kidney failure occurs, dialysis or a kidney transplant will be necessary.
Within the first year of life, children have signs of nephrotic syndrome. These may include:
A Wilms tumor develops in about 9 out of 10 children who have DDS. This is a cancerous (malignant) tumor. It can affect one or both kidneys, grow large and spread in the body. Symptoms may include:
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Male children with DDS have the expected male chromosome pattern (46, XY). But their internal and external sex organs aren’t typical (disorders of sexual development). Features may include:
This combination can lead to the genitals having both male and female features (ambiguous genitals).
Female children can also have DDS, but their external genitals look as expected. However, like the testicles in male children, the ovaries may not develop as expected.
All children who have Denys-Drash syndrome develop kidney disease (nephropathy). It progresses to kidney failure before they reach the age of 3. Kidney tumors also develop in almost all children with DDS.
Abnormal development of the testicles and ovaries (gonads) increases the risk of developing cancer (gonadoblastoma). It can also lead to infertility and problems making sex hormones in the future (delayed puberty).
Other long-term effects may include:
A genetic variation in the Wilms tumor suppressor gene 1 (WT1) causes Denys-Drash syndrome. The WT1 gene makes a protein that regulates kidneys and gonads during fetal development. When these organs don’t develop as expected, it can lead to problems with how your child’s kidneys work and how their external genitals look. It also increases the risk of developing a Wilms tumor.
DDS follows an autosomal dominant pattern of inheritance. That means only one biological parent needs to have the changed gene to pass it on to their child.
Because DDS is so rare, it may take some time to get an official diagnosis. Your child’s healthcare provider can usually diagnose atypical genitals at birth. If they suspect kidney problems, they may recommend:
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Your child’s provider may also recommend specialists to help make a Denys-Drash syndrome diagnosis and form a treatment plan. These may include a:
Your child’s healthcare providers will work with you to create a plan that considers all of the risks. Keeping your child’s kidneys working for as long as possible is important. Their initial treatment may include:
Once your child’s kidneys no longer work well enough, treatment includes dialysis. Dialysis does the work of the kidneys. Providers may also recommend removing both kidneys (bilateral nephrectomy) to prevent Wilms tumors. Your child may also receive a kidney transplant.
If a Wilms tumor develops, treatment may include surgery and chemotherapy or radiation therapy.
Your child’s healthcare provider may also recommend removing the testicles or ovaries (gonadectomy). They sometimes recommend this because screening for testicular or ovarian cancer can be challenging.
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For atypical genitals, you’ll work with your child’s providers to determine the best treatment for their long-term well-being. This includes future sexual function and possible fertility. Treatment may include hormone replacement therapy (HRT) and, if medically necessary, reconstructive surgery. If it isn’t medically necessary, some parents choose to hold off on surgery that changes the appearance of their child’s genitals. They may wait until their child is old enough to make decisions about their body.
If your child has Denys-Drash syndrome, it’s important to schedule regular appointments so providers can monitor their kidney health. Contact a provider right away if you notice any signs of kidney failure. These include:
Because it’s rare, there isn’t a lot of information on long-term outcomes.
Your child will need close supervision by a team of specialists. The care team will regularly check on how well your child’s kidneys are working. As kidney function declines, your child will need tests, medications and procedures to keep their kidneys working for as long as possible. When kidney failure happens, your child will need dialysis or a kidney transplant to survive.
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If your child’s kidneys fail or they get a Wilms tumor, they need surgery to remove their kidneys (nephrectomy). If they have a Wilms tumor, they may need additional treatment, including chemotherapy and/or radiation therapy.
In male children with atypical testicles, surgical removal (orchiectomy) or repositioning (orchiopexy) may be needed. They may also need a few separate penile reconstruction surgeries to create a functional, typical-looking penis.
As your child gets older, atypical genitals can have a big impact on their mental health. Your child’s providers may recommend a counselor or therapist to help them navigate any complicated feelings. They can also help determine the best possible course of treatment.
A specific gene variation causes DDS. In most cases, the variation happens spontaneously. That means a biological parent doesn’t pass it down.
Your healthcare provider may recommend genetic counseling and testing if you or your partner have a biological family history of Denys-Drash syndrome or other conditions that involve the same WT1 gene variation. These include:
Genetic counseling helps you learn more about the risk of your child having these conditions.
Finding out your child has a rare genetic disorder is a challenge many parents don’t expect. And because Denys-Drash syndrome affects vital organs and how your child’s external genitals look, it can be even more distressing. It’s normal to have a wide range of feelings. Your child’s healthcare providers also expect you to have a lot of questions. They can guide you through the most appropriate treatments for your child to help ensure the best outcome.
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Cleveland Clinic’s health articles are based on evidence-backed information and review by medical professionals to ensure accuracy, reliability and up-to-date clinical standards.
Cleveland Clinic’s health articles are based on evidence-backed information and review by medical professionals to ensure accuracy, reliability and up-to-date clinical standards.
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