National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Denys-Drash syndrome


Other Names:
Drash syndrome; Wilms tumor and pseudohermaphroditism; Nephropathy, wilms tumor, and genital anomalies; Drash syndrome; Wilms tumor and pseudohermaphroditism; Nephropathy, wilms tumor, and genital anomalies; Pseudohermaphroditism, nephron disorder and Wilms' tumor; Nephropathy associated with male pseudohermaphroditism and Wilms' tumor See More
Categories:
Denys-Drash syndrome is a condition that affects the kidneys and genitalia. Kidney disease typically begins in the first few months of life, often leading to kidney failure in childhood. In addition, up to 90 percent of people with this condition develop a rare form of kidney cancer known as Wilms tumor. Males with Denys-Drash syndrome have gonadal dysgenesis, a condition in which the external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear to be completely female. The testes are also undescended, meaning that they remain in the pelvis, abdomen, or groin. Affected females usually have normal genitalia. For this reason, females with this condition may be diagnosed with isolated nephrotic syndrome. Denys-Drash syndrome is caused by mutations in the WT1 gene. This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, most cases result from new mutations in the gene and occur in people with no history of the disorder in their family.[1]
Last updated: 10/28/2013

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Male pseudohermaphroditism 0000037
Nephroblastoma 0002667
Nephropathy 0000112
Nephrotic syndrome 0000100
Proteinuria
High urine protein levels
Protein in urine
[ more ] 		0000093
30%-79% of people have these symptoms
Hypertension 0000822
5%-29% of people have these symptoms
Gonadal dysgenesis 0000133
Percent of people who have these symptoms is not available through HPO
Ambiguous genitalia, female
Atypical appearance of female genitals
0000061
Ambiguous genitalia, male
Ambiguous genitalia in males
0000033
Autosomal dominant inheritance 0000006
Congenital diaphragmatic hernia 0000776
Diffuse mesangial sclerosis 0001967
Focal segmental glomerulosclerosis 0000097
Gonadal tissue inappropriate for external genitalia or chromosomal sex 0003248
Ovarian gonadoblastoma 0000149
Somatic mutation 0001428
Stage 5 chronic kidney disease 0003774
True hermaphroditism 0010459
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Last updated: 7/1/2020
Denys-Drash syndrome is caused by mutations in the WT1 gene. This gene provides instructions for making a protein (the WT1 protein) that regulates the activity of other genes by attaching (binding) to specific regions of DNA. The WT1 protein plays a role in the development of the kidneys and gonads (ovaries in females and testes in males) before birth.[1]

The WT1 gene mutations that cause Denys-Drash syndrome lead to the production of an abnormal protein that cannot bind to DNA. As a result, the activity of certain genes is unregulated, which impairs the development of the kidneys and reproductive organs. Abnormal development of these organs leads to diffuse glomerulosclerosis (where scar tissue forms throughout glomeruli, the tiny blood vessels in the kidney that filter waste from blood) and gonadal dysgenesis, which are characteristic features of Denys-Drash syndrome. The abnormal gene activity caused by the loss of normal WT1 protein also increases the risk of developing Wilms tumor in affected individuals.[1]
Last updated: 6/3/2015
Denys-Drash syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of Denys-Drash syndrome result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development. These cases occur in people with no history of the disorder in their family.[1]
Last updated: 6/3/2015

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnosis includes WAGR syndrome, Frasier syndrome, Meacham syndrome, congenital nephrotic syndrome of the Finnish type, idiopathic nephrotic syndrome, and isolated diffuse mesangial sclerosis
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Denys-Drash syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Denys-Drash syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Denys-Drash syndrome. Click on the link to view a sample search on this topic.

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  1. Denys-Drash syndrome. Genetics Home Reference (GHR). March 2013; http://ghr.nlm.nih.gov/condition/denys-drash-syndrome. Accessed 6/3/2015.