Definition
Three phenotypes are involved – WAGR syndrome (WAGR, OMIM#194072), Denys-Drash syndrome (DDS, OMIM #194080), and Frasier syndrome (FS, OMIM #136680), which occur in people with different genetic defects of the WT1 gene and are associated with an increased risk of Wilms tumors and other abnormalities.
Key Data
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| Synonym | |
| Gene | WT1 |
| Gene product | WT1 |
| Function | WT1 encodes for a zinc finger protein with multiple isoforms. The gene product is a transcription factor that regulates cell growth and the differentiation of the kidneys, gonads, spleen, and mesothelium. |
| Heredity | Autosomal dominant |
| Prevalence | Rare |
| Genotype-phenotype correlation | The mutation type determines whether WAGR, DDS, or FS is present. The greatest risk of nephroblastoma is linked to truncating mutations in the exon 8/9 hotspot. Patients with truncating mutations have a higher risk of bilateral nephroblastomas than patients with missense mutations.
|
| Penetrance | Unknown |
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Diagnosis
Diagnosis
The diagnosis is made clinically and can be verified by means of mutation analysis.
Differential Diagnoses
Clinical Presentation
WAGR
Wilms tumor, aniridia, urogenital malformation, mental retardation; Wilms tumor risk 30-60%
DDS
Diffuse mesangial sclerotization, early kidney failure, genital malformations, gonadal dysgenesis; Wilms tumor risk 74-90%
FS
Focal segmental glomerulosclerosis, gonadal dysgenesis, genital malformations; Wilms tumor risk not greatly increased
Grundsätzlich
WT1-associated gonadoblastomas may occur when sexual development is disrupted in individuals with FS or DDS who have a 46,XY karyotype. In these patients, the development of gonadoblastomas appears to be closely linked to the presence of gonadal dysgenesis, and it appears to occur with FS and DDS at approximately the same frequency (in over 40% of patients). Even though most gonadoblastomas develop in adolescents and young adults, these tumors have also been diagnosed in toddlers. The gonadoblastoma risk is low in individuals with matching karyotype and gender.
Therapeutic Considerations
Individuals suffering from WT1-associated syndromes should be cared for by a multi-professional team consisting of experienced nephrologists, pediatric oncologists, etc.
The treatment of a patient who has a Wilms tumor with WAGR, DDS, or FS should be discussed with the principal investigator of the nephroblastoma study.
All individuals with FS or DDS and a 46,XY karyotype should be checked for the presence of gonadal dysgenesis. If a gonadal dysgenesis is confirmed, a gonadectomy is recommended. With regard to the specific approach, we refer to the following recommendations:
Surveillance Recommendations
Surveillance Recommendations
Ultrasound of the kidneys every 3 months until the age of 7
Additional Information
Open Clinical Trials / Registries
Support Groups
Unfortunately, we are as yet unaware of any existing support groups for patients with WT1-Associated Syndrome. We will add new information as it becomes available.
