• Test code: 01743
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit

Invitae WT1-Related Disorders Test

Test description

This test analyzes the WT1 gene, which is associated with isolated Wilms tumor and with syndromic causes of Wilms tumor, including WAGR (Wilms, aniridia, genitourinary, retardation), Denys-Drash syndrome (DDS), and Frasier syndrome.

Genetic testing of WT1 may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (1 gene)

Alternative tests to consider

Rarely, cases of Wilms tumor are due to a contiguous gene deletion that encompasses both the PAX6 and WT1 genes and that causes Wilms tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome. In the presence of any of aniridia, the WAGR syndrome test, which includes the PAX6 gene, may be more appropriate.

  • WT1-related disorders
    • Denys-Drash syndrome (DDS)
    • Frasier syndrome
    • WAGR syndrome (wilms tumor, aniridia, genitourinary, retardation)
    • isolated Wilms tumor

Wilms tumor
(Nephroblastoma) is an embryonal renal cancer that is made up of some combination of blastemal, epithelial, and stromal cells and is the most common renal malignancy in childhood. Hereditary pathogenic variants in WT1 explain approximately 5% of Wilms tumor cases. Such variants can cause non-syndromic isolated Wilms tumor as well as syndromes of which Wilms is a feature—particularly WAGR (Wilms, aniridia, genitourinary, retardation), Denys-Drash (DDS), and Frasier syndromes.

WAGR syndrome
WAGR syndrome is caused by a deletion on chromosome 11 inclusive of both WT1 and the PAX6 gene, which is associated with aniridia (absence of color in the iris). Aniridia is typically the first noticeable sign of WAGR syndrome. In individuals with WAGR syndrome, Wilms tumor presents earlier and is more often bilateral than in isolated Wilms tumor cases. Intellectual disability is common, as are psychiatric or behavioral problems. The most common genitourinary anomalies in males is cryptorchidism. Females may have underdeveloped ovarian tissue and bicornuate uterus, leading to fertility issues.

Denys-Drash syndrome (DDS)
DDS is a condition that affects the kidneys and genitalia. Renal disease, specifically diffuse glomerulosclerosis, begins within the first year of life and often leads to kidney failure. The risk for Wilms tumor is greater than 90%. Affected males have ambiguous genitalia due to gonadal dysgenesis and may be infertile. Because affected females typically have normal genitalia and only manifest the renal features of DDS, they are often diagnosed with isolated nephrotic syndrome.

Frasier syndrome
Frasier syndrome is similar to DDS, affects the kidneys and genitalia. Childhood-onset renal disease—specifically focal segmental glomerulosclerosis—often leads to kidney failure in adolescence. Affected males have ambiguous genitalia and underdeveloped internal gonads that may require surgical removal due to risks of gonadoblastoma. Because affected females typically have normal genitalia and gonads and only manifest the renal features, they are often diagnosed with isolated nephrotic syndrome. Wilms tumor has been reported in some cases, but it is not a primary feature. Due to the significant clinical overlap with DDS, it is suspected that Frasier and DDS may be variable clinical presentations of the same condition.

In addition to the syndromes above, some individuals with pathogenic variants in WT1 may present with genitourinary anomalies and Wilms tumor in the absence of renal failure.

ConditionWilms tumorGonadoblastomaReferences (PMIDs)
Non-syndromic WT1 pathogenic variants Elevated - 12193442, 25688735
WAGR syndrome 40%–50% - 11479730, 11920832
Denys-Drash syndrome Estimated 90% 40% 15150775, 8827067, 25623218, 20301471
Frasier syndrome Elevated 60% 25623218

Elevated: There is evidence of association, but penetrance or risk is not well characterized.

WT1-related disorders are inherited in an autosomal dominant manner. Though a few cases are inherited, most occur as the result of a spontaneous de novo pathogenic variant.

  • Wilms tumor affects 1 in 8,000 to 1 in 10,000 children in North America. It is the most common pediatric kidney cancer and accounts for 6.3% of all cancers in children under age 15.
  • WAGR syndrome occurs in 1 in 500,000 to 1 in one million individuals. Approximately one-third of those diagnosed with aniridia have underlying WAGR and roughly 1 in 143 cases of Wilms tumor are due to WAGR.
  • Denys-Drash and Frasier syndromes are rare; their exact prevalence is currently unknown.

Analysis of the WT1 gene may be considered in individuals with a personal and/or family history of:

  • Wilms tumor
  • aniridia
  • genitourinary anomalies
  • renal disease or renal failure

  1. Dome, JS, Huff, V. Wilms Tumor Overview. 2003 Dec 19. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301471
  2. Pritchard-Jones, K. Controversies and advances in the management of Wilms' tumour. Arch. Dis. Child. 2002; 87(3):241-4. PMID: 12193442
  3. Kaneko, Y, et al. A high incidence of WT1 abnormality in bilateral Wilms tumours in Japan, and the penetrance rates in children with WT1 germline mutation. Br. J. Cancer. 2015; 112(6):1121-33. PMID: 25688735
  4. Breslow, N, et al. Epidemiology of Wilms tumor. Med. Pediatr. Oncol. 1993; 21(3):172-81. PMID: 7680412
  5. Miller, RW, et al. Childhood cancer. Cancer. 1995; 75(1 Suppl):395-405. PMID: 8001010
  6. Ezaki, J, et al. Gonadal tumor in Frasier syndrome: a review and classification. Cancer Prev Res (Phila). 2015; 8(4):271-6. PMID: 25623218
  7. Grønskov, K, et al. Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia. Hum. Genet. 2001; 109(1):11-8. PMID: 11479730
  8. Muto, R, et al. Prediction by FISH analysis of the occurrence of Wilms tumor in aniridia patients. Am. J. Med. Genet. 2002; 108(4):285-9. PMID: 11920832
  9. Royer-Pokora, B, et al. Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development. Am. J. Med. Genet. A. 2004; 127A(3):249-57. PMID: 15150775
  10. Huff, V. Genotype/phenotype correlations in Wilms' tumor. Med. Pediatr. Oncol. 1996; 27(5):408-14. PMID: 8827067
  11. Auber, F, et al. Management of Wilms tumors in Drash and Frasier syndromes. Pediatr Blood Cancer. 2009; 52(1):55-9. PMID: 18816692
  12. Wu, HY, et al. Wilms' tumor management. Curr Opin Urol. 2005; 15(4):273-6. PMID: 15928519
  13. National Library of Medicine. Genetics Home Reference. WT1 - Wilms tumor 1. http://ghr.nlm.nih.gov/gene/WT1 Accessed August 2015.
  14. American Cancer Society, cancer.org: What are the risk factors for Wilms tumor? http://www.cancer.org/cancer/wilmstumor/detailedguide/wilms-tumor-risk-factors Accessed September 2019.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below, depending on the specific gene or test. In addition, the analysis covers select non-coding variants. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
WT1 NM_024426.4