1. Home
  2. Cancer genetics
  3. Paediatric
  4. Risk management

Wilms tumour – risk management

On this page
Expand all Collapse all Back to top

Wilms tumour or nephroblastoma is the most common renal malignancy of childhood affecting approximately 1 in 10,000 children. Up to 30% of children with Wilms tumour will have a genetic or epigenetic variant that increases their risk of Wilms tumour.r

Predisposition in Wilms tumour can be broadly divided into two categories:

  • Syndromic Wilms
    • large and diverse group of conditions, each with a recognised pattern of clinical features and inheritance r
  • Non-syndromic Wilms​
    • known/described genetic/epigenetic variant that increases risk of Wilms tumour
    • familial history of Wilms with no identified genetic variant (familial Wilms tumour) 

The care of an individual who has developed a related tumour or cancer should be individualised based on their clinical situation, their family history and the monitoring they need as part of their treatment and post-treatment follow-up.

  • Phenotypic features consistent with a known syndrome associated with a greater than 1% lifetime risk of Wilms tumour
  • Unaffected known or obligate carrier of a genetic variant associated with a greater than 1% increased risk of Wilms tumour
  • Unaffected child who has 2 or more relatives with non-syndromic Wilms tumour in the family where a genetic variant has not been identified (familial Wilms tumour)

Exclusion criteria

  • Children already diagnosed with Wilms tumour
  • Phenotypic features consistent with a known syndrome associated with a less than 1% lifetime risk of Wilms tumour
  • Unaffected known or obligate carrier of a genetic variant associated with a less than 1% increased risk of Wilms tumour
  • Beckwith-Wiedemann syndrome (see Beckwith Wiedemann syndrome - risk management)
  • Individual with a variant of uncertain significance
Syndrome/genetic variants Risk of Wilms tumour by age 18 yearsrr
High risk of Wilms tumour (>20%) - surveillance recommended

Beckwith-Wiedemann syndrome

ICI GOM

See Beckwith-Wiedemann syndrome - risk management

24%
CTR9 (truncating/splicing variants) Unclear; may be >20%
Familial Wilms (2 or more family members with Wilms but no causative variant identified) 30%

Fanconi anaemia

Biallelic PALB2* 

Biallelic BRCA2*

 

40%

20%

Mosaic variegated aneuploidy

Biallelic BUB1B*

Biallelic TRIP13*

 

Around 50%

Around 20%
Perlman syndrome (biallelic DIS3L2) up to 65%
WAGR syndrome (del 11p13 including WT1 and PAX9) 50%

WT1 disorder

exonic truncating variant

exonic missense variant

See GeneReviews® WT1 Disorder

80%

50%
Moderate risk of Wilms tumour (3-20%) - surveillance recommended

Beckwith-Wiedemann syndrome

UPD(11)pat

See Beckwith-Wiedemann syndrome - risk management

7%
Bloom syndrome (BLM)* 3%
Hemihyperplasia (no causative variant identified)* up to 4%
Mulibrey nanism (TRIM27) 9%
REST Unknown, but appears moderately increased
Simpson-Golabi-Behmel syndrome (GPC3) ≤10% (males)
TRIM28 Unknown, but appears moderately increased
Low risk/insufficient evidence of association with Wilms tumour - surveillance not recommended

Beckwith-Wiedemann syndrome

IC2 LOM

CDKN1C*

See Beckwith-Wiedemann syndrome - risk management

0.2%

1.4%
Bohring-Opitz syndrome (ASXL1)* Unknown, few case reports only and causal link to Wilms tumour not yet established
CDC73 Unknown, few case reports only and causal link to Wilms tumour not yet established
CTCF Unknown, single case report only and causal link to Wilms tumour not yet established
DICER1 syndrome*

Unknown, but appears low. Note – renal screening for cystic nephroma recommended

See DICER1 – risk management (child)
FBXW7 Unknown, few case reports only and causal link to Wilms tumour not yet established
Li-Fraumeni syndrome (TP53)*

Unknown but appears low. Note – renal screening for adrenocortical carcinoma recommended

See TP53 - risk management (child)
NYNRIN (biallelic variants) Unknown, few case reports only and causal link to Wilms tumour not yet established
Osteopathia striata with cranial sclerosis (AMER1) Unknown, few case reports only and causal link to Wilms tumour not yet established
PIK3CA- related segmental overgrowth <0.5%

*Risk of other malignancies 

The choice of risk management strategy should take into account current age, other health issues, age-related cancer risk and the estimated risk associated with the underlying genetic diagnosis. Risks and benefits of interventions should be discussed with an experienced medical professional.

The impact of lifestyle on cancer risk should be discussed e.g. exercise most days for at least 30 minutes at moderate or strenuous intensity, maintain a healthy weight, have a healthy diet, limit alcohol intake, do not smoke and avoid excess sun exposure.

For individuals with a genetic diagnosis within the high and moderate risk category, the recommended risk management strategy is outlined below.

Cancer/tumour type Recommendations
High risk of Wilms tumour (>20%) Surveillance recommended Age to begin Strategy and frequency
From birth or diagnosis
  • Recommend renal ultrasound every 3 months until age 7 years
  • Consider specialist physical examination twice yearly
Moderate risk of Wilms tumour (3-20%) Surveillance recommended From birth or diagnosis
  • Recommend renal ultrasound every 3 months until age 7 years
  • Consider specialist physical examination twice yearly
Low risk/insufficient evidence of association with Wilms tumour Surveillance not recommended N/A N/A

A diverse number of conditions are implicated in predisposition to the development of Wilms tumour and each condition may be associated with a unique array of health problems. These need to be appropriately identified and followed up.

There is limited data on the effectiveness of surveillance in children at increased risk of Wilms tumour. There is lack of international consensus on the threshold at which to offer surveillance. These recommendations represent expert opinion taking into account both the potential benefits of surveillance and the potential harms and burdens.

Where the Wilms tumour risk is low, or there is insufficient evidence of a gene’s association with Wilms tumour, surveillance is not recommended as there is no evidence for utility and the burden of surveillance is high.

Surveillance

There is limited evidence about the efficacy of Wilms tumour surveillance in children at high/moderate risk of Wilms tumour. Wilms tumour predispositions are rare, and this limits the ability of clinical researchers to perform large prospective studies to address the utility of surveillance. In addition, there are uncertainties regarding the risk and natural history of Wilms tumour in predisposing conditions.

Retrospective studies have shown that children with Beckwith-Wiedemann syndrome spectrum undergoing surveillance for Wilms tumour had lower stage Wilms tumour when compared to children not undergoing surveillance.r

To date international expert opinions support of surveillance in children who are at increased risk of Wilms tumour due to the reasonable assumption that early detection of Wilms tumour will reduce the morbidity associated with the disease and its management through reduced treatment burden.rr In particular, smaller lesions are more likely to be amenable to nephron-sparing surgery reducing the lifetime risk of renal impairment. The frequency of imaging is based on the expected growth trajectory of Wilms tumour. Approximately 95% of cases of Wilms tumour have presented prior to age 7 years and so surveillance should continue until this age.r After the age of 7, investigation for Wilms tumour should be guided by individual health history, residual Wilms tumour risk and risk tolerance of the provider, affected individual, and family.

For the syndromic forms of Wilms tumour there are other non-cancer management issues and there may also be an increased risk of other primary cancers. The relevant literature and clinical guidelines should be consulted. 

[%id%]
[%title%]
[%abstract%]

Version 5

Date Summary of changes
11/09/2024

Protocol reviewed at paediatric cancer genetics reference committee meeting on 14 June 2024. Discussions continued via email and MS Teams. Approved for publication with the following changes made:

  • Risk of cancer/tumour: table revised
  • Cancer/tumour risk management guidelines: section revised. Separate rows added in table for high risk, moderate risk and low risk/insufficient evidence of association with Wilms tumour
  • Evidence for risk management guidelines: minor wording changes

Version increased to V.5. Approved on 30/08/2024, published on 11/09/2024. Review in 2 years.

Version 4

Date Summary of changes
15/09/2023

New eviQ cancer genetics risk management template changes applied - PDF of changes.

Version number changed to V.4.

Version 3

Date Summary of changes
13/02/2023

The following sections of the document were updated to align with the new eviQ cancer genetics risk management template:

  • Summary: 
    • Template sentence updated.
  • Target population:
    • Added to exclusion criteria "Individual with a variant of uncertain significance".
  • Cancer/tumour risk management guidelines:
    • Template sentence updated.
    • Lifestyle factors sentence moved above table.
  • Management of associated health problems:
    • Accordion title changed to "Management of associated health issues".

Version number increased to V.3.

Version 2

Date Summary of changes
15/12/2022

Protocol reviewed at the cancer genetics paediatric reference committee meeting June 2022. Summary of changes:

  • Summary: 'familial' definition updated
  • Risk of cancer/tumour:
    • table updated with moderate risk category changed from 5-20% to 3-20%. Low risk category changed from <5% to <2%
  • Cancer/tumour risk management guidelines: information on low risk group added
  • Evidence: minor updates

Version increase V.2. Review in 2 years.

Version 1

Date Summary of changes
02/12/2020 New protocol developed and discussed by the cancer genetics paediatric reference committee at the July 2019 and February 2020 reference committee meetings. Discussions continued via email. Protocol approved for publication as V.1. Review in 1 year.
14/10/2021 Hyperparathyroid-jaw tumour syndrome removed from Risk of cancer/tumour table.

The information contained in this document is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to care or treatment. Any clinician seeking to apply or consult this document is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

Send feedback for this page

First approved:
Last reviewed:
Review due:

The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/3702

11 Oct 2024