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Wilms Tumor




The etiology of Wilms tumor remains unclear. The tumor may arise in 3 clinical settings:

  1. Sporadic
  2. Association with genetic syndromes
  3. Familial/hereditary


Genetic Syndromes

  • 9% of children with Wilms tumor have one of several syndromes. This is one of the highest proportions seen in any childhood malignancy. Syndrome manifestations vary and an affected child may not have all associated traits.


The WAGR syndrome

  • Wilms tumor
  • Aniridia (lack of an iris)
  • Genitourinary malformations and mental retardation
  • linked to a specific chromosome deletion:
    • This syndrome is associated with deletion of the short arm of chromosome 11, band 13 (11p13).
    • The WAGR deletions encompass a number of contiguous genes including the aniridia gene PAX6 and the Wilms tumor suppressor gene WT1.
    • WT1 gene is important in normal kidney development.
    • WT1 is located within the short arm of one copy of chromosome 11p13.
    • The loss or mutation of one WT1 allele results in the genitourinary defects and constitutes the first event required for the development of Wilms tumor.
  • Occurs only in male children.

Although mutation of WT1 is the initiating event in Wilms tumors arising in patients with WAGR, it is far more limited, but important in sporadic Wilms tumor.

Characteristics of genes associated with WAGR:


Loss of an allele is responsible for aniridia
This gene is responsible for the development of the brain, the eye, and nasal tissue


  • Wilms tumor suppressor gene
  • Loss or mutation of one WT1 allele results in the genitourinary defects and constitutes the first event required for the development of Wilms tumor
  • Mutations are far less common in sporadic Wilms tumor
  • Very important gene in normal kidney development



Other Associated Genetic Syndromes include Beckwith-Wiedemann, Denys-Drash and Perlman syndrome. They are summarized in the table below:

Beckwith-Wiedemann Syndrome (BWS)

The major features of BWS include:

  1. Macroglossia
  2. Defects of closure of the abdominal wall
  3. Visceromegaly (liver, kidney, spleen)
  4. Muscular hypertrophy
  5. Advanced bone age
  6. Hemi-hypertrophy

Malignant tumor development occurs in about 8% of children with BW and the most common of these is Wilms tumor.


Most BWS cases are sporadic, however, familial cases do occur with an autosomal dominant pattern of inheritance and showing variable penetrance and expressivity.



  • The genetic locus for BWS is also present on the short arm of chromosome 11 (11p15)
  • The second Wilms tumor suppressor gene located at this site is called WT2
  • WT2 has effects on IGF2, the H19 tumor suppressor gene and a P57 cell cycle regulator

Denys-Drash Syndrome (DDS)

The major features include:

  1. Nephropathy (usually fatal unless there is a renal transplant)
  2. Dysgenetic male pseudohermaphroditism
  3. Wilms tumor

Perlman Syndrome (PS)

Has some features in common with BWS, but it is a distinct syndrome
The major features include:


Characteristic facial appearance:

    1. Macrocephaly
    2. Small, short nose with depressed nasal bridge
    3. Deep-set eyes
    4. Low-set ears

Macrosomia and organomegaly are common to PS and BWS, however, other features of BWS are not seen.


PS appears to show an autosomal recessive pattern of inheritance.


Increased risk for Wilms tumor


Genetics and prognosis:

  • Gain of chromosome 1q is one of the most common cytogenetic abnormalities in Wilms tumour.  It is observed in approximately 30% of tumors and is associated with an inferior outcome.
  • Patients who have loss of heterozygosity (loss of chromosomal material and called LOH) on the long arm of chromosome 16 (16q) or the short arm of chromosome 1 (1p) have a poor prognosis.
  • LOH at either 1p or 16q showed trends toward increased risks of relapse or death, but the greatest effect was seen with combined LOH at both loci, found in approximately 5% of favorable histology Wilms tumors

The acquisition of TP53 mutations have been associated with the development of Wilms tumor with anaplastic histology. Anaplastic histology is associated with poorer prognosis. 


Hereditary or familial Wilms

  • Defined as bilateral disease or a family history of Wilms.
  • Relatively rare.
  • Inheritance is usually dominant and occurs without other congenital abnormalities.
  • Familial cases appear at an earlier age than unilateral disease.
  • Genes implicated in familial Wilms include WT1, FWT1 and FWT2.


Additional factors

  • There is no convincing evidence that paternal occupation plays an etiological role1 .
  • Previous epidemiological studies of Wilms tumor have suffered from a number of methodological limitations:
    • inadequate sample size
    • poor exposure assessment
    • low survey response rates
    • limited control of confounding factors
    • inability to evaluate potential etiologic heterogeneity of cases defined by biologic and other characteristics



High incidence of malformation syndromes in a series of 1,073 children with cancer. Merks JH1, Caron HN, Hennekam R



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