• Test code: 01742
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Wilms Tumor Panel

Test description

This test analyzes four genes that are associated with both isolated and syndromic causes of Wilms tumor, including WAGR (Wilms, aniridia, genitourinary, retardation), Denys-Drash syndrome (DDS), Beckwith-Wiedemann syndrome, Frasier syndrome, Simpson-Golabi-Behmel syndrome, and Perlman syndrome.

It is important to establish a diagnosis so that appropriate clinical management guidelines can be implemented and accurate recurrence risks determined. Early diagnosis and treatment can reduce morbidity and increase longevity. With testing, at-risk relatives can be identified, enabling pursuit of a diagnostic evaluation, early detection, and improved clinical outcome.

Order test

Primary panel (4 genes)

Alternative tests to consider

These genes can also be ordered as part a broader panel to test for hereditary cause of renal/urinary tract cancer. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional charge.

  • Beckwith-Wiedemann syndrome (BWS)
  • Perlman syndrome
  • Simpson-Golabi-Behmel syndrome
  • WT1-related disorders
    • Denys-Drash syndrome (DDS)
    • Frasier syndrome
    • WAGR syndrome (wilms, 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. Several genes are associated with both syndromic and nonsyndromic forms of Wilms tumor, including CDKN1C, DIS3L2, GPC3 and WT1. Variants in these genes can cause nonsyndromic isolated Wilms tumor as well as syndromes of which Wilms is a feature. These conditions include the following:

Beckwith-Wiedemann syndrome
This syndrome is an overgrowth condition with features including hemihyperplasia, omphalocele, umbilical hernia, macroglossia, visceromegaly, creases or pits in the skin near the ears, and neonatal hypoglycemia. Affected individuals have an increased risk of developing multiple benign and malignant tumors—particularly Wilms tumor, hepatoblastoma, and rhabdomyosarcoma. This panel assesses for pathogenic variants in the CDKN1C gene, which account for 40% of familial cases of Beckwith-Wiedemann syndrome and 5% of cases with no reported family history of the condition (10424811, 11414765).

Simpson-Golabi-Behmel syndrome type 1 (SGBS1)
SGBS1 is a rare, X-linked overgrowth disorder that is a result of pathogenic variants in the GPC3 gene. This condition presents in the prenatal or neonatal period. Affected males typically have intellectual disability, macrosomia, cardiac, skeletal, gastrointestinal and genitourinary anomalies, hepatosplenomegaly, and a distinctive facies that includes macrocephaly, coarse facial features, macrostomia, and macroglossia. There is an increased risk for embryonal tumors, including Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, and hepatocellular carcinoma (NCBI GeneReviews. Simpson-Golabi-Behmel Syndrome Type 1. Accessed September 2015).

Perlman syndrome
Perlman syndrome is a rare overgrowth condition that is the result of pathogenic variants in DIS3L2. This disorder is characterized by fetal/neonatal macrosomia, polyhydramnios, nephromegaly, distinctive facial appearance, developmental delay, renal dysplasia, nephroblastomatosis, and predisposition to Wilms tumor. The prognosis of Perlman syndrome is poor, with a high neonatal mortality rate. Among the infants who survive beyond the neonatal period, the risk of developing Wilms tumor is approximately 64% (22306653).

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 this condition. Wilms tumor due to WAGR syndrome occurs earlier than in isolated cases of Wilms tumor and is more often bilateral. Intellectual disability is common, as are psychiatric and behavioral problems. The most common genitourinary anomaly in males is cryptorchidism. Females may have underdeveloped ovarian tissue and bicornuate uterus, leading to fertility issues.

Denys-Drash syndrome (DDS)
DDS is the result of pathogenic variants in the WT1 gene. This condition primarily 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 manifest only the renal features of DDS and have normal genitalia, they are often diagnosed with isolated nephrotic syndrome.

Frasier syndrome
Like DDS, Frasier syndrome is the result of pathogenic variants in WT1 and 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 manifest only the renal features and have normal genitalia and gonads, 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.

The genes on this panel are associated with hereditary Wilms tumor, but the overall percentage of hereditary cancer cases caused by these risk factors is currently unclear. Inclusion of multiple Wilms-related genes is expected to increase the clinical sensitivity of this test.

Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant can present differently, even among family members. Because we cannot predict which cancers may develop, most individuals who are found to have a pathogenic variant will be offered screening tests to detect and prevent cancer.

ConditionWilms tumorGonadoblastomaReferences (PMIDs)
Non-syndromic WT1 pathogenic variants elevated _ 12193442, 25688735
WAGR syndrome 40%–50% _ 11479730, 11920832
Denys-Drash syndrome 90% 40% 15150775, 8827067, 25623218, 20301471
Perlman syndrome 64% _ 22306653
Frasier syndrome elevated 60% 25623218
Simpson-Golabi-Behmel syndrome elevated elevated 16398453
Beckwith-Wiedemann syndrome up to 8% _ 12138139

Isolated and syndromic causes of Wilms tumor can be inherited in different patterns depending on the gene:

  • CDKN1C and WT1:- autosomal dominant
  • DIS3L2: autosomal recessive
  • GPC3: X-linked

Wilms tumor affects 1 in 8,000–10,000 children in North America (7680412). It is the most common pediatric kidney cancer and accounts for 6.3% of all cancers in children under age 15 (8001010). Most cases are sporadic, but approximately 10%–15% are due to a hereditary pathogenic variant in a disease-causing gene that may or may not be associated with a known syndrome.

  • 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.
  • Beckwith-Wiedemann syndrome occurs in approximately 1 in 13,700 individuals.
  • Denys-Drash and Frasier syndromes are rare; their exact prevalence is currently unknown.
  • The prevalence of Perlman syndrome is currently unknown and appears to be rare.
  • The prevalence of Simpson-Golabi-Behmel syndrome is currently unknown and appears to be rare.

This panel may be considered for individuals with a personal and/or family history of:

  • Wilms tumor
  • findings such as developmental delay, macrosomia, dysmorphic craniofacial features, cardiac, gastrointestinal, and genitourinary anomalies suggestive of an underlying syndrome

  1. Bahubeshi, A, et al. Germline DICER1 mutations and familial cystic nephroma. J. Med. Genet. 2010; 47(12):863-6. doi: 10.1136/jmg.2010.081216. PMID: 21036787
  2. Slade, I, et al. DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J. Med. Genet. 2011; 48(4):273-8. doi: 10.1136/jmg.2010.083790. PMID: 21266384
  3. de, Kock, L, et al. Exploring the association Between DICER1 mutations and differentiated thyroid carcinoma. J. Clin. Endocrinol. Metab. 2014; 99(6):E1072-7. doi: 10.1210/jc.2013-4206. PMID: 24617712
  4. Wu, Y, et al. DICER1 mutations in a patient with an ovarian Sertoli-Leydig tumor, well-differentiated fetal adenocarcinoma of the lung, and familial multinodular goiter. Eur J Med Genet. 2014; 57(11-12):621-5. doi: 10.1016/j.ejmg.2014.09.008. PMID: 25451712
  5. de, Kock, L, et al. Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. Acta Neuropathol. 2014; 128(1):111-22. doi: 10.1007/s00401-014-1285-z. PMID: 24839956
  6. Cao, WM, et al. Germline mutations of DICER1 in Chinese women with BRCA1/BRCA2-negative familial breast cancer. Genet. Mol. Res. 2014; 13(4):10754-60. doi: 10.4238/2014.December.18.16. PMID: 25526195
  7. de, Kock, L, et al. Germ-line and somatic DICER1 mutations in pineoblastoma. Acta Neuropathol. 2014; 128(4):583-95. doi: 10.1007/s00401-014-1318-7. PMID: 25022261
  8. Rio, Frio, T, et al. DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors. JAMA. 2011; 305(1):68-77. doi: 10.1001/jama.2010.1910. PMID: 21205968
  9. Golabi, M, et al. Simpson-Golabi-Behmel Syndrome Type 1. 2006 Dec 19. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1219/ PMID: 20301398
  10. Morris, MR, et al. Perlman syndrome: overgrowth, Wilms tumor predisposition and DIS3L2. Am J Med Genet C Semin Med Genet. 2013; 163C(2):106-13. PMID: 23613427
  11. Dome, JS, Huff, V. Wilms Tumor Overview. 2003 Dec 19. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301471
  12. Goldman, M, et al. Renal abnormalities in beckwith-wiedemann syndrome are associated with 11p15.5 uniparental disomy. J. Am. Soc. Nephrol. 2002; 13(8):2077-84. PMID: 12138139
  13. Pritchard-Jones, K. Controversies and advances in the management of Wilms' tumour. Arch. Dis. Child. 2002; 87(3):241-4. PMID: 12193442
  14. Gracia, Bouthelier, R, Lapunzina, P. Follow-up and risk of tumors in overgrowth syndromes. J. Pediatr. Endocrinol. Metab. 2005; 18 Suppl 1:1227-35. PMID: 16398453
  15. 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
  16. Cohen, MM. Beckwith-Wiedemann syndrome: historical, clinicopathological, and etiopathogenetic perspectives. Pediatr. Dev. Pathol. 2005; 8(3):287-304. PMID: 16010495
  17. Astuti, D, et al. Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nat. Genet. 2012; 44(3):277-84. PMID: 22306653
  18. DeBaun, MR, et al. Nephromegaly in infancy and early childhood: a risk factor for Wilms tumor in Beckwith-Wiedemann syndrome. J. Pediatr. 1998; 132(3 Pt 1):401-4. PMID: 9544890
  19. Breslow, N, et al. Epidemiology of Wilms tumor. Med. Pediatr. Oncol. 1993; 21(3):172-81. PMID: 7680412
  20. Miller, RW, et al. Childhood cancer. Cancer. 1995; 75(1 Suppl):395-405. PMID: 8001010
  21. Ezaki, J, et al. Gonadal tumor in Frasier syndrome: a review and classification. Cancer Prev Res (Phila). 2015; 8(4):271-6. PMID: 25623218
  22. Lam, WW, et al. Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation. J. Med. Genet. 1999; 36(7):518-23. PMID: 10424811
  23. Li, M, et al. Imprinting status of 11p15 genes in Beckwith-Wiedemann syndrome patients with CDKN1C mutations. Genomics. 2001; 74(3):370-6. PMID: 11414765
  24. 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
  25. 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
  26. 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 August 2015.

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, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CDKN1C NM_000076.2
DIS3L2 NM_152383.4
GPC3 NM_004484.3
WT1 NM_024426.4