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Wilms Tumor Predisposition

, MD, PhD and , PhD.

Author Information

Initial Posting: ; Last Update: October 20, 2016.



This GeneReview is intended to help clinicians determine if a genetic basis can be identified in an individual with Wilms tumor in order to provide families with natural history and recurrence risk information.

Goal 1.

Briefly describe the clinical characteristics of Wilms tumor.

Goal 2.

Review the mechanisms of predisposition to Wilms tumor.

Goal 3.

Provide an evaluation strategy to:

  • Determine if a proband with Wilms tumor has a predisposition to Wilms tumor;
  • Identify the genetic or epigenetic mechanism for Wilms tumor; and
  • Determine risks for additional medical complications.

Goal 4.

Discuss genetic counseling issues including mode of inheritance, recurrence risk, and evaluation of relatives at risk based on the underlying genetic mechanism.

Goal 5.

Discuss management (e.g., tumor screening) recommendations for individuals with a genetic predisposition to Wilms tumor.

Clinical Characteristics of Wilms Tumor

Wilms tumor (nephroblastoma), an embryonal malignancy of the kidney, is the most common renal tumor of childhood. It usually presents as an abdominal mass in an otherwise apparently healthy child. Abdominal pain, fever, anemia, hematuria, and hypertension are seen in 25%-30% of affected children.

Approximately 5%-10% of individuals with Wilms tumor have bilateral or multicentric tumors. The prevalence of bilateral involvement is higher in individuals with a predisposition to Wilms tumor than in those without a genetic predisposition (see Mechanisms of Predisposition to Wilms Tumor).

A definitive diagnosis of Wilms tumor can be made only on histologic assessment of the tumor.

Nephrogenic rests, benign foci of embryonal kidney cells that persist abnormally into postnatal life, are considered to be Wilms tumor precursors. Pathogenic variants may predispose to nephrogenic rests. Additional pathogenic variants transform nephrogenic rests into a Wilms tumor [Dome & Coppes 2002].

Mechanisms of Predisposition to Wilms Tumor

In 10%-15% of individuals with Wilms tumor, the cause is considered to be a germline pathogenic variant or an epigenetic alteration occurring early during embryogenesis (see 11p15-Related Wilms Tumor). These may or may not be associated with a known congenital malformation syndrome or hereditary cancer syndrome.

Approximately 1%-2% of individuals with Wilms tumor have at least one relative also diagnosed with Wilms tumor (familial Wilms tumor); however, while germline variants that are likely pathogenic have been identified in some families, they are still not known for the majority of individuals.

The most commonly reported germline genetic and epigenetic variants in individuals with Wilms tumor involve WT1 and the 11p15.5 locus. A growing number of variants in other genes have been reported. In some cases, the estimated of risk of Wilms tumor with these variants is high, but the variant or syndrome is so rare in the general population that only a handful of individuals with Wilms tumor have ever been reported. For example, among eight individuals reported with mosaic variegated aneuploidy and germline monoallelic BUB1B variants, seven (87.5%) had Wilms tumor. However, only about ten individuals with mosaic variegated aneuploidy and Wilms tumor have ever been reported. The following sections describe WT1- and 11p15-related Wilms tumor in depth. Table 1 summarizes other variants and syndromes that have been associated with Wilms tumor.

WT1-Related Wilms Tumor

Heterozygous germline WT1 pathogenic variants have been identified in some individuals with Wilms tumor without syndromic features, in some families with Wilms tumor, in individuals with WAGR syndrome (Wilms tumor, aniridia, genital anomalies, retardation), Denys-Drash syndrome (DDS), and Frasier syndrome, and in individuals with genitourinary anomalies without renal failure.

Wilms Tumor Without Syndromic Features

Germline WT1 pathogenic variants have a greater effect on sex determination and genital tract development in males; therefore, females with a germline WT1 pathogenic variant are less likely to exhibit genitourinary anomalies. Individuals with germline WT1 pathogenic variants are more likely to have bilateral or multicentric tumors and to develop tumors at an early age [Royer-Pokora et al 2004]. In the absence of genitourinary anomalies, renal mesangial sclerosis, or bilateral tumors, the likelihood that a child with Wilms tumor has a germline WT1 pathogenic variant is low, with reported frequencies of 0%-5% [Huff 1998, Little et al 2004, Segers et al 2012].

Familial Wilms Tumor

Although pathogenic variants in WT1 are not implicated in most families with Wilms tumor predisposition, a small number of families have heterozygous germline WT1 pathogenic variants [Grundy et al 1988, Huff et al 1988, Diller et al 1998, Huff 1998].

WAGR Syndrome

WAGR syndrome (Wilms tumor, aniridia, genital anomalies, retardation) is characterized by Wilms tumor, aniridia, hemihypertrophy, genitourinary abnormalities, ambiguous genitalia, gonadoblastoma, and intellectual disability.

Genetic alteration. A heterozygous contiguous gene deletion at 11p13 that includes both WT1 and PAX6 is causative. Aniridia arises from deletion of PAX6, which lies within approximately 0.6 Mb of WT1.

Risk for Wilms tumor. The risk for Wilms tumor in individuals with WAGR syndrome is estimated at between 45% and 60% [Muto et al 2002, Fischbach et al 2005]. The risk for Wilms tumor in simplex cases (i.e., a single occurrence of aniridia in a family) is 40%-50% if the individual has an 11p13 deletion that includes WT1. Wilms tumor has not been reported in two large series of individuals with aniridia and PAX6 alterations if WT1 deletion is not detected by FISH [Grønskov et al 2001, Muto et al 2002].

Individuals with WAGR syndrome have an earlier age of Wilms tumor diagnosis and more frequent occurrence of bilateral disease than other individuals with Wilms tumor. Among individuals with Wilms tumor and WAGR syndrome, 90% develop Wilms tumor by age four years and 98% by age seven years [Beckwith 1998b]. Of note, they also have a high incidence of intralobar nephrogenic rests and their tumors invariably exhibit a favorable histology. Individuals with WAGR syndrome have short-term survival comparable to persons who do not have WAGR syndrome [Breslow et al 2003]. However, individuals with a germline WT1 pathogenic variant are more likely to have a stromal histology of Wilms tumor called fetal rhabdomyomatous nephroblastoma [Royer-Pokora et al 2004]. This histologic subtype has clinical implications because it may not shrink and sometimes grows in response to chemotherapy, which impedes surgical resection.

Other findings. Individuals with WAGR syndrome often develop end-stage renal disease (ESRD) around adolescence, resulting in declining survival. In studies employing the National Wilms Tumor Studies (NWTS) patient population, 34%-40% of individuals with WAGR syndrome who survived a Wilms tumor subsequently developed ESRD. A 48% (±17%) survival rate at age 27 years from diagnosis of Wilms tumor was estimated for this group [Breslow et al 2000, Breslow et al 2003, Breslow et al 2005].

Denys-Drash Syndrome

Denys-Drash syndrome (DDS) is characterized by diffuse mesangial sclerosis leading to early-onset renal failure, intersex disorders that can range from ambiguous to normal-appearing female in both XY & XX individuals, and a high risk of Wilms tumor.

Genetic alteration. The majority of individuals with DDS have a heterozygous germline missense pathogenic variant in WT1 exon 8 or 9 [Royer-Pokora et al 2004]. While other types of WT1 pathogenic variants in a small number of affected individuals are reported in the literature, they are often in individuals diagnosed as having DDS in the absence of renal failure [Royer-Pokora et al 2004].

Risk for Wilms tumor. In one large study, 74% of children with DDS developed Wilms tumor. The risk for Wilms tumor in individuals with DDS is likely higher than reported, as children with DDS often undergo kidney transplants or die of end-stage renal failure before the (potential) development of tumors [Eddy & Mauer 1985, Mueller 1994].

Other findings. Renal failure in individuals with DDS tends to be earlier onset. The NWTS reported that the cumulative incidence of renal failure in those with DDS, 20 years after Wilms tumor diagnosis, was 74% [Breslow et al 2005].

Frasier Syndrome

Frasier syndrome (FS) is characterized by undermasculinized external genitalia that can range from ambiguous to normal-appearing female in an individual with a 46,XY karyotype, focal segmental glomerulosclerosis, and gonadoblastoma. While originally considered distinct from DDS, the observation of individuals displaying phenotypes classically ascribed to both DDS and FS, including a child with a germline WT1 deletion who was diagnosed with both Wilms tumor and gonadoblastoma, has led to the suggestion that DDS and FS represent two ends of a phenotypic spectrum [Koziell et al 2000, Finken et al 2015].

Genetic alteration. Heterozygous single-nucleotide variants in the WT1 intron 9 donor splice site are the predominant type of alteration observed in individuals diagnosed with FS [Barbaux et al 1997].

Risk for Wilms tumor. Wilms tumors are not typically observed in individuals with WT1 intron 9 variants. However, the suggestion that DDS and FS represent a single syndrome of variable phenotypes implies that individuals diagnosed with FS may be at risk for Wilms tumor.

Genitourinary (GU) Anomalies Without Renal Failure

Some individuals with germline WT1 alterations have GU anomalies and Wilms tumor, but do not have early renal failure. A summary of 117 individuals with germline WT1 alterations who were ascertained via a diagnosis of Wilms tumor or Wilms tumor-related phenotypes indicated that a third displayed no evidence of renal failure at the time of Wilms tumor diagnosis [Royer-Pokora et al 2004]. However, as renal failure can develop at later ages [Breslow et al 2000], the proportion of individuals carrying a WT1 germline alteration who do not ultimately develop renal failure is expected to be less.

Genetic alteration. These findings are predominantly associated with WT1 deletions and nonsense and frameshift variants.

11p15.5-Related Wilms Tumor

Beckwith-Wiedemann Syndrome

Beckwith-Wiedemann syndrome (BWS) is characterized by macrosomia, macroglossia, hemihyperplasia, visceromegaly, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), omphalocele, neonatal hypoglycemia, ear creases/pits, adrenocortical cytomegaly, and renal abnormalities.

Genetic alteration. BWS is associated with abnormal regulation of gene transcription in an imprinted domain on chromosome 11p15.5 (see Beckwith-Wiedemann Syndrome).

Risk for Wilms tumor. Wilms tumor occurs in approximately 7% of children with BWS. Uniparental disomy of 11p15.5 or gain of methylation at imprinting center 1 (IC1) is associated with the highest risk for Wilms tumor in BWS; a quarter of children with these alterations developed Wilms tumor. Among individuals with BWS and Wilms tumor, 81% develop the tumor by age five years and 93% develop the tumor by age eight years [Beckwith 1998a, Rump et al 2005, Weksberg et al 2010].

Wilms Tumor Without Syndrome Features

Wilms tumor without syndrome features can be associated with alterations of chromosome 11p15.5 including gain of methylation at IC1, paternal uniparental disomy of 11p15.5, and genomic abnormalities including microdeletion and microinsertion [Scott et al 2008].

Less Common Causes of Wilms Tumor Predisposition

Table 1.

Less Common Causes of Wilms Tumor Predisposition.

GeneSyndromeEstimated Wilms Tumor RiskReferences
BLMBloom syndrome∼3%Moreira et al [2013]
BRCA2Fanconi anemia (FA-D1)∼20%Reid et al [2005], Scott et al [2006]
BUB1BMosaic variegated aneuploidy (MVA) (OMIM)∼25% overall in MVA
>85% in individuals w/BUB1B pathogenic variants
Callier et al [2005], García-Castillo et al [2008]
CDC73Hyperparathyroid-jaw tumor syndrome (OMIM)∼3%Kakinuma et al [1994], Szabó et al [1995]
CTR9Familial Wilms tumor3 families reported
6/9 individuals w/a CTR9 pathogenic variant in these families had Wilms tumor.
Hanks et al [2014]
DICER1DICER1-related disordersLow risk w/most DICER1 variants
Higher risk (2/11; 18%) in individuals w/Gly803Arg variant
Foulkes et al [2011], Palculict et al [2016]
DIS3L2Perlman syndrome (OMIM)∼30%Scott et al [2006], Astuti et al [2012]
GPC3, GPC4Simpson-Golabi-Behmel type 14%-9%Lapunzina [2005], Scott et al [2006]
PALB2Fanconi anemia (FA-N)∼40%Reid et al [2007]
PIK3CAPIK3CA-related segmental overgrowth1%-2%Gripp et al [2016]
RESTFamilial Wilms tumor (OMIM)
Additional clinical features reported in several affected individuals
4 families reported
7/14 individuals w/a REST pathogenic variant in these families had Wilms tumor.
9 nonfamilial Wilms tumor
Mahamdallie et al [2015]
TP53Li-Fraumeni syndromeLow, but several cases reportedBirch et al [2001], Schlegelberger et al [2015]
TRIM37Mulibrey nanism (OMIM)6%Scott et al [2006], Karlberg et al [2009]
UnknownTrisomy 1812 individuals reported w/Wilms tumor 1Scott et al [2006], Shanske [2006]
UnknownTrisomy 132 individuals reported w/Wilms tumor 1Olson et al [1995], Sweeney & Pelegano [2000]

Given early mortality, the risk for Wilms tumor may be higher than indicated by the number of individuals reported.

Evaluation Strategy

The following approach can be used to determine if a proband with Wilms tumor has a predisposition to Wilms tumor, to identify the genetic or epigenetic mechanism for Wilms tumor, and to determine risks for additional medical complications. Establishing the genetic mechanism for a predisposition to Wilms tumor involves a medical history, family history, physical examination, and molecular genetic testing.

Clinical Findings

Physical features suggestive of a WT1-related Wilms tumor include aniridia, genitourinary anomalies (including ambiguous genitalia), renal insufficiency or failure, and intellectual disability. Features suggestive of Beckwith-Wiedemann syndrome (BWS) include macrosomia, ear creases/pits, macroglossia, omphalocele, visceromegaly, other embryonal tumors (e.g., hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), hemihyperplasia, adrenocortical cytomegaly, and renal abnormalities. Physical features may also be observed in other syndromes that predispose to Wilms tumor (see Table 1).

In addition to physical features, radiologic or histologic findings may indicate the possibility of genetic predisposition to Wilms tumor. The presence of bilateral or multifocal Wilms tumor is suggestive of a genetic predisposition. Nephrogenic rests may provide corroborative evidence for Wilms tumor predisposition, although more than 25% of individuals with unilateral, seemingly sporadic Wilms tumor have nephrogenic rests in kidney tissue that is free of tumors [Beckwith 1993]. Hence, the presence of nephrogenic rests in the absence of other features does not warrant a molecular genetic evaluation. The histologic finding of fetal rhabdomyomatous nephroblastoma should raise awareness of WT1 variants, which may be germline or restricted to the tumor tissue.

Family History

Given the rarity of Wilms tumor in the population, the existence of a relative with Wilms tumor is suggestive of a genetic predisposition.

Molecular Genetic Testing

Molecular genetic testing should be considered in individuals with Wilms tumor who have physical, radiologic, or histologic features suggestive of a genetic predisposition. Testing should also be considered if an affected individual has a family member with Wilms tumor. Molecular genetic testing can include single-gene testing, gene-targeted deletion/duplication analysis, methylation studies, use of a multi-gene panel, and chromosomal microarray (CMA). The choice of test should be based on the clinical features.

Individuals with Wilms Tumor Without Syndromic Features

WT1. Sequence analysis of WT1 is performed first. Gene-targeted deletion/duplication analysis may be performed to detect intragenic deletions.

11p15.5. Methylation studies of 11p15.5 imprinting center 1 (IC1) can be performed if a germline WT1 pathogenic variant is not identified. Of note, in individuals with Beckwith-Wiedemann syndrome (BWS) and Wilms tumor, only IC1 (IGF2/H19 genes), not IC2, alterations have been observed [Rump et al 2005, Weksberg et al 2010].

A multi-gene panel that includes WT1, REST, DICER1 and other genes of interest (see Table 1) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and over time. (2) Some multi-gene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multi-gene panel provides the best opportunity to identify the genetic cause of the condition at the most reasonable cost while limiting secondary findings. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing based tests. (4) Multi-gene panels may not include DNA methylation analysis used to detect 11p15.5 alterations.

Individuals with Wilms Tumor and Genitourinary Anomalies or Renal Failure

WT1. Sequence analysis of WT1 is performed first and followed by gene-targeted deletion/duplication analysis of WT1 if a pathogenic variant is not identified.

Individuals with Wilms Tumor and Physical Features of BWS

11p15.5. Methylation studies of 11p15.5 IC1 should be performed first in individuals with features of BWS. (See Beckwith-Wiedemann Syndrome for additional testing issues.)

Individuals with Wilms Tumor and Aniridia

Chromosomal microarray (CMA) should be performed first in individuals with suspected WAGR (Wilms tumor, aniridia, genital anomalies, retardation). CMA can detect 11p13 deletions encompassing WT1 and PAX6 as well as provide detailed information regarding size of the deletion. CMA also gives information regarding deletions and duplications in the remainder of the genome. CMA-SNP array will allow detection of uniparental disomy at 11p15.5 in cases with long stretches of homozygosity.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Individuals with Wilms tumor who have features suggestive of a genetic predisposition (bilateral or multifocal Wilms tumor, syndromic features or congenital anomalies associated with Wilms tumor, or family history of Wilms tumor) should receive genetic counseling. Individuals with unilateral Wilms tumor with no features to suggest a genetic predisposition do not require molecular testing or genetic counseling. No Wilms tumor was observed in the 179 offspring of 96 long-term survivors who had been diagnosed with unilateral, non-familial Wilms tumor [Li et al 1988].

Syndromic Wilms tumor

Nonsyndromic Wilms tumor associated with a germline WT1 pathogenic variant

  • Mode of inheritance. WT1 germline variants are inherited in an autosomal dominant manner with variable expressivity and reduced penetrance [Zirn et al 2005].
  • Parents of a proband. In the majority of individuals with a WT1 germline variant, the pathogenic variant occurred de novo; parents are unlikely to have had Wilms tumor or to have the germline WT1 variant.
  • Sibs of a proband. When the WT1 pathogenic variant identified in the proband cannot be detected in the DNA of either parent, the risk to the sibs of a proband is likely to be low; however, the rate of parental germline mosaicism is unknown [Huff 1994].
  • Offspring of a proband are at a 50% risk of inheriting the WT1 germline pathogenic variant. The risk of Wilms tumor developing in a child with a known WT1 germline variant depends on the penetrance of the specific variant.

Nonsyndromic Wilms tumor not associated with a WT1 pathogenic variant

  • Parents of a proband. Most individuals diagnosed with nonsyndromic Wilms tumor do not have an affected parent, but some may have another affected family member (i.e., familial Wilms tumor).
  • Sibs of a proband
    • Simplex case. Empiric risks to the sibs of a proband who is the only affected family member are unknown but likely low.
    • Familial case. Empiric risks to the sibs of a proband who does not have an identified WT1 germline pathogenic variant of developing Wilms tumor are unknown. In most cases, the genetic variant underlying the risk of Wilms tumor will be unknown, but several genes other than WT1 (e.g., REST, CTR9 and BRCA2) have been associated with familial Wilms tumor. The risk to a sib depends on the variant involved.
  • Offspring of a proband
    • Simplex case. Empiric risks to the offspring of a proband who is the only affected family member are unknown but likely low.
    • Familial case. Empiric risks to the offspring of a proband with another affected family member are estimated to be high, based on the assumption of inheritance of a dominantly acting allele with incomplete penetrance.

Bilateral or multifocal nonsyndromic Wilms tumor

  • The presence of bilateral or multifocal disease in the proband implies that the proband has a genetic predisposition. However, the majority of individuals with bilateral Wilms tumor have neither a WT1 germline pathogenic variant (16% have a WT1 germline pathogenic variant) nor an affected family member (3% have affected family members).
  • The risk to offspring of a proband with bilateral or multifocal disease is estimated to be high, but the risk varies with the gene in which the pathogenic variant occurred. Ultrasound screening of the offspring for Wilms tumor in childhood should be considered.

Related Genetic Counseling Issues

See Management, Surveillance for Relatives at Risk for Wilms Tumor Predisposition for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Genetic cancer risk assessment and counseling. For a comprehensive description of the medical, psychosocial, and ethical ramifications of identifying at-risk individuals through cancer risk assessment with or without molecular genetic testing, see Cancer Genetics Risk Assessment and Counseling – for health professionals (part of PDQ®, National Cancer Institute).

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once a causative genetic alteration (e.g., WT1 pathogenic variant, alteration of 11p15.5, DICER1, or REST pathogenic variant) has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible options.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.


Surveillance of Children with a Germline Pathogenic Variant or with Wilms Tumor-Associated Syndromes

General considerations. The goal of surveillance in individuals with a genetic predisposition to Wilms tumor is to detect tumors while they are low-stage and require less treatment compared to advanced-stage tumors. Surveillance is not a one-time event and should continue through the period of risk, estimated to be until age five to eight years, depending on the underlying genetic condition. Wilms tumors can double in size every week [Beckwith 1998a], leading to the authors’ recommendation that evaluation with abdominal ultrasound be performed every three months. Because surveillance is associated with economic and psychosocial costs including missed work, anxiety associated with exams, and false-positive results leading to unnecessary interventions, the decision to pursue surveillance requires careful consideration. Weighing the risks and benefits of surveillance, Scott et al [2006] suggested that surveillance be pursued if the risk for tumor development is greater than 5%.

Individuals with a germline WT1 pathogenic variant. Screening by abdominal ultrasound examination is recommended every three months until age five years. Among individuals with Wilms tumor and WAGR syndrome, 90% develop a tumor by age four years and 98% by age seven years [Beckwith 1998b].

Individuals with an 11p15.5 alteration, Beckwith-Wiedemann syndrome (BWS), or isolated hemihyperplasia have a 5% to 7.5% risk of developing Wilms tumor or other malignancies (mainly hepatoblastoma, adrenocortical carcinoma, neuroblastoma, and rhabdomyosarcoma). However, risk of Wilms tumor is restricted to certain subtypes of BWS.

A meta-analysis by Rump et al [2005] of more than 400 individuals with BWS for whom molecular data at 11p15 were available indicated that:

  • Wilms tumor was not observed in children with:
  • Wilms tumor was observed in children with:

Hence, surveillance may be restricted to individuals with uniparental isodisomy at 11p15, gain of methylation at imprinting center 1, or BWS in whom a genetic or epigenetic abnormality is not found. Children with isolated methylation changes of imprinting center 2 or a CDKN1C pathogenic variant do not require surveillance for Wilms tumor. When surveillance is pursued, abdominal ultrasound examination is recommended every three months until age eight years. Among individuals with BWS and Wilms tumor, 81% develop the tumor by age five years and 93% develop the tumor by age eight years [Beckwith 1998a].

Individuals with one of the less common causes of Wilms tumor predisposition. The authors recommend surveillance if the estimated risk for Wilms tumor associated with the genetic variant exceeds 5%. The recommendation can be adjusted depending on the individual preference of the family and treating physician. If the risk period has not been established, surveillance with abdominal ultrasound is recommended every three months until age eight years.

Individuals with bilateral or multifocal Wilms tumor without an identified molecular cause. After completion of therapy for Wilms tumor, individuals should be screened by renal ultrasound examination every three months until age eight years for metachronous tumors. It is assumed that most individuals with bilateral Wilms tumor have a germline variant in a gene predisposing to Wilms tumor, increasing the risk for a metachronous tumor.

Surveillance for Relatives at Risk for Wilms Tumor Predisposition

In families with more than one individual with Wilms tumor and families with one individual with bilateral or multifocal Wilms tumor, it is appropriate to evaluate relatives at risk in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures. Evaluations can include the following:

  • Molecular genetic testing if the causative genetic alteration has been identified in an affected family. Surveillance with ultrasound may be pursued if the Wilms tumor risk associated with the causative variant is sufficiently high.
  • If the causative genetic alteration has not been identified in an affected family member:
    • Offspring of the affected individual should be screened with abdominal ultrasound examination every three months until age eight years.
      Note: The risk for Wilms tumor in the children of survivors of bilateral Wilms tumor is unknown.
    • The benefit of surveillance of sibs of the affected individual is unclear. Only 3% of individuals with bilateral Wilms tumor had an affected family member, indicating that the risk to a sib is even lower than 3%. Surveillance of sibs would not be recommended if applying the threshold risk of tumor greater than 5% as an indication for surveillance.


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Suggested Reading

  1. Breslow NE, Ou SS, Beckwith JB, Haase GM, Kalapurakal JA, Ritchey ML, Shamberger RC, Thomas PR, D'Angio GJ, Green DM. Doxorubicin for favorable histology, Stage II-III Wilms tumor: results from the National Wilms Tumor Studies. Cancer. 2004;101:1072–80. [PubMed: 15329918]
  2. DeBaun MR, Niemitz EL, McNeil DE, Brandenburg SA, Lee MP, Feinberg AP. Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. Am J Hum Genet. 2002;70:604–11. [PMC free article: PMC384940] [PubMed: 11813134]
  3. Dome JS, Roberts CWM, Argani P. Pediatric renal tumors. In: Orkin SH, Ginsburg D, Nathan DG, Look AT, Fisher DE, Lux SE, eds. Oncology of Infancy and Childhood. Amsterdam, Netherlands: Elsevier Academic Publishers; 2009:541-73.
  4. Engel JR, Smallwood A, Harper A, Higgins MJ, Oshimura M, Reik W, Schofield PN, Maher ER. Epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome. J Med Genet. 2000;37:921–6. [PMC free article: PMC1734494] [PubMed: 11106355]
  5. Fernandez C, Geller JI, Ehrlich PF, Hill DA, Kalapurakal JA, Grundy PE, Dome JS. Renal tumors. In: Pizzo P, Poplack D, eds. Principles and Practice of Pediatric Oncology. 6 ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2011:861-85.
  6. Green DM, Breslow NE, Beckwith JB, Finklestein JZ, Grundy PE, Thomas PR, Kim T, Shochat SJ, Haase GM, Ritchey ML, Kelalis PP, D'Angio GJ. Comparison between single-dose and divided-dose administration of dactinomycin and doxorubicin for patients with Wilms' tumor: A report from the National Wilms' Tumor Study Group. J Clin Oncol. 1998;16:237–45. [PubMed: 9440748]
  7. Grundy RG, Pritchard J, Scambler P, Cowell JK. Loss of heterozygosity for the short arm of chromosome 7 in sporadic Wilms tumour. Oncogene. 1998;17:395–400. [PubMed: 9690521]
  8. Trepanier A, Ahrens M, McKinnon W, Peters J, Stopfer J, Grumet SC, Manley S, Culver JO, Acton R, Larsen-Haidle J, Correia LA, Bennett R, Pettersen B, Ferlita TD, Costalas JW, Hunt K, Donlon S, Skrzynia C, Farrell C, Callif-Daley F, Vockley CW. Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors. J Genet Couns. 2004;13:83–114. [PubMed: 15604628]
  9. Tycko B. Epigenetic gene silencing in cancer. J Clin Invest. 2000;105:401–7. [PMC free article: PMC289180] [PubMed: 10683367]
  10. Weksberg R, Nishikawa J, Caluseriu O, Fei YL, Shuman C, Wei C, Steele L, Cameron J, Smith A, Ambus I, Li M, Ray PN, Sadowski P, Squire J. Tumor development in the Beckwith-Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1. Hum Mol Genet. 2001;10:2989–3000. [PubMed: 11751681]

Chapter Notes

Revision History

  • 20 October 2016 (sw) Comprehensive update posted live
  • 19 September 2013 (me) Comprehensive update posted live
  • 14 June 2011 (me) Comprehensive update posted live
  • 10 April 2006 (me) Comprehensive update posted to live Web site
  • 24 May 2004 (cd) Revision: Genetic Counseling
  • 19 December 2003 (me) Overview posted to live Web site
  • 14 July 2003 (jsd) Original submission
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