Clinical characteristics.

WT1 disorder is characterized by congenital/infantile or childhood onset of steroid-resistant nephrotic syndrome (SRNS), a progressive glomerulopathy that does not respond to standard steroid therapy. Additional common findings can include disorders of testicular development (with or without abnormalities of the external genitalia and/or müllerian structures) and Wilms tumor. Less common findings are congenital anomalies of the kidney and urinary tract (CAKUT), gonadoblastoma, and 46,XX gonadal dysgenesis. In adulthood, most individuals are affected by early gonadal insufficiency of variable severity with potential impact on puberty and fertility. While various combinations of renal and other findings associated with a WT1 pathogenic variant were designated as certain syndromes in the past (the most common being Denys-Drash and Frasier syndromes), those designations are now recognized to be part of a phenotypic continuum and are no longer clinically helpful.

Diagnosis/testing.

The diagnosis of WT1 disorder is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in WT1 identified by molecular genetic testing.

Management.

Treatment of manifestations: SRNS: avoid immunosuppressants; consider renin-angiotensin-aldosterone system (RAAS) inhibition. Disorders of testicular development and 46,XX gonadal dysgenesis: management is often by a multidisciplinary team (clinical geneticist, endocrinologist, urologist, and psychologist). Treat Wilms tumor with standard oncology protocols and, when applicable, nephron-sparing surgery. Treat CAKUT per standard care. Prevent whenever possible gonadoblastoma by prophylactic gonadectomy in those with a disorder of testicular development. Diaphragmatic hernia repair prior to the start of peritoneal dialysis.

Surveillance: Monitor for first appearance of the following: proteinuria every six months until age ten years, yearly thereafter; Wilms tumor every three months until age seven years; early gonadal insufficiency yearly after puberty. For ongoing issues with disorders of testicular development and 46,XX gonadal dysgenesis, monitor per treating multidisciplinary team, and for CAKUT, monitor per treating nephrologist and/or urologist.

Agents/circumstances to avoid: Avoid treating glomerulopathy with immunosuppressants, as they are not effective and potentially toxic.

Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an individual with WT1 disorder in order to identify as early as possible those who would benefit from prompt initiation of treatment and surveillance for glomerulopathy and Wilms tumor.

Genetic counseling.

WT1 disorder is inherited in an autosomal dominant manner. Most individuals diagnosed with WT1 disorder have the disorder as the result of an apparent de novo WT1 pathogenic variant; in rare instances, a parent of an individual with WT1 disorder is heterozygous for the pathogenic variant identified in the proband. If a parent of the proband is affected and/or is known to have the WT1 pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%. If the WT1 pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population because of the possibility of parental gonadal mosaicism. Once the WT1 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Suggestive Findings

WT1 disorder should be suspected in an individual with the following clinical, imaging, and supportive laboratory findings.

Establishing the Diagnosis

The diagnosis of WT1 disorder is established in a proband with suggestive clinical findings and a heterozygous pathogenic (or likely pathogenic) variant in WT1 identified by molecular genetic testing (see Table 1).

Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this GeneReview is understood to include likely pathogenic variants. (2) Identification of a heterozygous WT1 variant of uncertain significance does not establish or rule out the diagnosis.

Molecular genetic testing approaches can include a combination of gene-targeted testing (single gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see Option 1), whereas comprehensive genomic testing does not (see Option 2).

Clinical Description

WT1 disorder is characterized by congenital/infantile or childhood onset of a progressive glomerulopathy that does not respond to standard steroid therapy. Additional common findings can include disorders of testicular development (with or without abnormalities of the external genitalia and/or müllerian structures) and Wilms tumor. Less common findings are congenital anomalies of the kidney and urinary tract (CAKUT), gonadoblastoma, and 46,XX gonadal dysgenesis (see Table 2). In adulthood, most individuals are affected by early gonadal insufficiency of variable severity with potential impact on puberty and fertility. While various combinations of renal and other findings associated with a WT1 pathogenic variant have in the past been designated as certain syndromes, those combinations are now recognized to be part of a phenotypic continuum and their designations are no longer clinically helpful (see Nomenclature) [Chernin et al 2010, Lipska et al 2014, Lehnhardt et al 2015, Ahn et al 2017].

Progressive glomerulopathy. Persistent proteinuria is the most common initial finding of the glomerulopathy in WT1 disorder. While the degree of proteinuria may fluctuate at the onset of renal involvement, it becomes progressively worse over time. The severity of the proteinuria varies among affected individuals, even within the same family. Note: Individuals with end-stage kidney failure may be anuric, and thus will not have proteinuria.

Steroid-resistant nephrotic syndrome (SRNS) – proteinuria, hypoalbuminemia, edema, and hyperlipidemia that does not respond to standard steroid therapy – is the characteristic kidney finding in WT1 disorder. SRNS can precede Wilms tumor by as much as four years, present at the time of Wilms tumor diagnosis, or develop after Wilms tumor (as much as 10 years after completion of the oncology treatment) [Lipska et al 2014, Lehnhardt et al 2015].

SRNS results in irreversible and progressive decline of kidney function and inevitably leads to end-stage kidney failure. Congenital nephrotic syndrome (nephrotic syndrome that presents in the first 3 months of life) is more rapidly progressive, resulting in end stage kidney failure within weeks to months [Boyer et al 2021].

Typical findings of the glomerulopathy on kidney biopsy are diffuse mesangial sclerosis reported primarily in children younger than age two years and focal segmental glomerulosclerosis in older individuals, although other diagnoses, including membranoproliferative glomerulonephritis, have also been reported [Anderson et al 2022]. Note: Because the histologic findings do not correlate with the clinical findings and because remarkable histopathologic heterogeneity is observed even among individuals with the same WT1 pathogenic variant [Lipska et al 2014, Lehnhardt et al 2015, Trautmann et al 2017], kidney biopsy is no longer considered a first-tier diagnostic measure for individuals of any age.

Wilms tumor. Wilms tumor (nephroblastoma) is one of the most common pediatric malignant solid tumors. The estimated risk to heterozygotes who have an exonic WT1 pathogenic variant of developing Wilms tumor is one tumor per nine years at risk. Calculation of the exact penetrance is hampered because a significant number of individuals with a WT1 pathogenic variant undergo prophylactic nephrectomy at the time of kidney transplantation or placement of a peritoneal dialysis catheter.

The median age at Wilms tumor diagnosis in WT1 disorder is significantly younger (median age: 1.3-1.6 years; range: 0-4.5 years) compared to Wilms tumor of unknown cause.

Bilateral tumors are more frequent in individuals with a truncating WT1 variant compared to individuals with other variants (>50% vs <15%) [Lipska et al 2014, Lehnhardt et al 2015] (see Genotype-Phenotype Correlations).

The survival rates for individuals with Wilms tumor caused by WT1 disorder do not differ significantly from those of individuals with Wilms tumor of unknown cause.

Genital findings. 46,XY individuals with WT1 disorder typically have a disorder of testicular development that is either a disorder of sex development (DSD) or complete gonadal dysgenesis (CGD) (see Table 2). 46,XY individuals with normal testes, normal male external genitalia, and normal fertility have been reported anecdotally.

46,XX individuals with a WT1 pathogenic variant typically have normal ovaries, normal female external genitalia, and müllerian structures that are usually normal (however, on occasion bicornuate uterus has been observed [Lipska et al 2014]) (see Table 2). 46,XX CGD has been reported in two 46,XX individuals with a WT1 pathogenic variant with absent ovaries [Ahn et al 2017, Roca et al 2019]. 46,XX DSD (testicular DSD or ovotesticular DSD) has been reported in seven individuals with a pathogenic variant in exon 10 encoding the fourth zinc finger of WT1 or within splicing sites involved in intron 9 splicing [Eozenou et al 2020].

In adulthood, most individuals are affected by early gonadal insufficiency of variable severity with potential impact on puberty and fertility [Carré Lecoindre et al 2024]. Premature gonadal failure was observed in persons with all karyotypes and genotypes irrespective of the timing of renal insufficiency.

Congenital anomalies of the kidney and urinary tract (CAKUT). CAKUT are observed in about 10% of individuals with WT1 disorder. The most common kidney abnormalities are duplex kidney, horseshoe kidney, and kidney malrotation. The most commonly reported urinary tract anomalies are vesicoureteral reflux, ureteropelvic junction stenosis, and urogenital sinus (in a 46,XX individual in whom both the urethra and vagina open into a common channel).

Gonadoblastoma. Individuals with 46,XY disorder of testicular development (either 46,XY DSD or 46,XY CGD) are at increased risk for germ cell tumors, particularly gonadoblastoma. The observed incidence is one gonadal tumor per 30 years at risk [Lipska et al 2014].

Because of the lack of long-term follow-up data, exact penetrance and long-term outcome are unknown. The survival rates for gonadoblastoma are excellent; however, if not treated it may result in malignant transformation of germ cells. A few instances of Sertoli tumor or other malignant testicular germ cell tumors have been reported [Kitsiou-Tzeli et al 2012, van Peer et al 2024].

Other. Diaphragmatic defect or herniation is a rare finding in WT1 disorder, reported in fewer than ten infants [Denamur et al 2000, Suri et al 2007, Ahn et al 2017].

Post-transplant lymphoproliferative disorder (PTLD) was reported in 7%-17% of individuals with WT1 disorder following kidney transplantation [Lipska et al 2014, Ahn et al 2017]. In all children undergoing kidney transplantation, the 25-year cumulative incidence of PTLD, adjusted for the competing risk of death, is 3.6% (95% CI: 2.7-4.8). Because of small numbers and lack of standardized follow-up data, it is not yet possible to determine if the frequency of PTLD is higher for WT1 disorder than for other children undergoing kidney transplantation.

Genotype-Phenotype Correlations

Recent developments have allowed delineation of genotype-phenotype correlations for certain subgroups of WT1 pathogenic variants (see also Table 1 in Nagano & Nozu [2025]).

Truncating pathogenic variants (all nonsense, frameshift, or splice-site variants that are not KTS [lysine, threonine, and serine] intron 9 variants; see Molecular Genetics) are associated with the following [Lipska et al 2014, Lehnhardt et al 2015, van Peer et al 2024, Glénisson et al 2025]:

• Wilms tumor is often the first clinical manifestation.
• Glomerulopathy. Proteinuria is typically diagnosed in the second decade of life in individuals who underwent unilateral or partial nephrectomy for Wilms tumor. The course of SRNS is slower.
• Genital anomalies secondary to a 46,XY DSD affect the vast majority of phenotypic males; 46,XY CGD is unlikely.
• The risk for bilateral Wilms tumor is the highest (odds ratio = 18.4).
• One in five individuals has CAKUT.

Missense pathogenic variants affecting nucleotides coding for amino acid residues in the DNA-binding region in exons 8 and 9 (see Molecular Genetics) are associated with the following [Lipska et al 2014, Nagano et al 2021, Glénisson et al 2025]:

• The risk for congenital nephrotic syndrome or early-onset rapidly progressive SRNS is the highest. By age 2.5 years, 50% of affected children have end-stage kidney failure.
• Of 46,XY individuals, approximately 80% have 46,XY DSD and 20% 46,XY CGD [BS Lipska-Ziętkiewicz, personal observation].

Missense pathogenic variants in exons 8 and 9 outside the DNA-binding region are associated with an intermediate glomerulopathy phenotype that manifests before age five years and progresses to end-stage kidney failure by about age ten years [Lipska et al 2014, Nagano et al 2021].

Certain donor splice-site pathogenic variants in intron 9 (see Molecular Genetics) are associated with the following [Chernin et al 2010, Lipska et al 2014, Lehnhardt et al 2015, Tsuji et al 2021]:

• Later onset and relatively slow progression of glomerulopathy that typically leads to end-stage kidney failure in adolescence
• 46,XY CGD in the majority of (but not all) 46,XY individuals and 46,XY DSD in a few individuals
• Highest risk for gonadoblastoma in CGD/DSD individuals, with risk of Wilms tumor significantly lower (≤3%)

Penetrance

The penetrance of WT1 disorder is high. It is age dependent, reaching about 90% by the end of puberty.

A few asymptomatic parents heterozygous for the same germline WT1 variant in their affected offspring have been reported [Fencl et al 2012, Lipska et al 2014, Kaneko et al 2015, Boyer et al 2017, Kirino et al 2023]. The penetrance appears to depend on the sex of the affected parent, with higher penetrance associated with paternal origin of the WT1 variant [Kaneko et al 2015]. However, current data on penetrance are limited because the variable expressivity of WT1 pathogenic variants was not recognized until recently, and the asymptomatic parents of a child with a WT1 pathogenic variant were not routinely tested.

Nomenclature

Frasier syndrome, Denys-Drash syndrome, and Meacham syndrome were originally described as distinct disorders on the basis of clinical findings but are now understood to represent a continuum of features caused by a WT1 heterozygous pathogenic variant. Given the extensive clinical overlap between these clinical diagnoses and molecular characterization of their shared genetic etiology, Frasier syndrome, Denys-Drash syndrome, and Meacham syndrome are no longer useful clinical diagnoses. However, these terms may still be used in the medical literature to refer to the following general phenotypic constellations:

• Frasier syndrome. SRNS, 46,XY CGD, and gonadoblastoma
• Denys-Drash syndrome. SRNS with diffuse mesangial sclerosis on kidney biopsy, Wilms tumor, and 46,XY DSD
• Meacham syndrome. Diaphragmatic hernia, pulmonary dysplasia, complex congenital heart defects, and genitourinary abnormalities including ambiguous genitalia and gonadal dysgenesis; in most reports, the condition was lethal early in infancy prior to development of other possible manifestations of WT1 disorder, such as SRNS or Wilms tumor. So far, none of the reported individuals with a confirmed WT1 pathogenic variant and a diaphragmatic defect had a complex congenital heart defect. A multigenic cause of this syndrome, with another as-yet-unknown gene responsible for the more severe cardiopulmonary phenotype, has been suggested [Suri et al 2007].

Male pseudohermaphroditism. The spectrum of clinical manifestations related to 46,XY DSD with a WT1 pathogenic variant was previously referred to using outdated terms such as male pseudohermaphroditism.

Prevalence

The prevalence of WT1 disorder is not known. Fewer than 500 affected individuals have been reported to date.

There are no WT1 founder variants or biased geographic distribution in specific populations.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with WT1 disorder, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Treatment of Manifestations

Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see Table 4).

Surveillance

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in Table 5 are recommended.

Agents/Circumstances to Avoid

Avoid treating glomerulopathy with immunosuppressants, as they are not effective and potentially toxic.

Evaluation of Relatives at Risk

It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual with WT1 disorder in order to identify as early as possible those who would benefit from prompt initiation of treatment and surveillance for glomerulopathy and Wilms tumor / gonadoblastoma.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Because kidney disease may progress during pregnancy, a pregnant woman with WT1 disorder should be referred promptly to a perinatal center experienced in the care of pregnant women with chronic kidney disease.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Mode of Inheritance

WT1 disorder is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

• Most individuals diagnosed with WT1 disorder have the disorder as the result of an apparent de novo WT1 pathogenic variant.
• In rare families, a parent of an individual with WT1 disorder is heterozygous for the pathogenic variant identified in the proband. Intrafamilial clinical variability is observed in WT1 disorder, and a heterozygous parent may be asymptomatic [Fencl et al 2012, Lipska et al 2014, Kaneko et al 2015, Boyer et al 2017, Kirino et al 2023] or have clinical manifestations of the disorder. For example:
  • Fencl et al [2012] described monozygotic twins presenting with congenital nephrotic syndrome born to an asymptomatic father age 41 years with the same WT1 pathogenic variant;
  • Guaragna et al [2013] described two families with vertical transmission of isolated WT1-related steroid-resistant nephrotic syndrome from an affected parent to an affected child.
• If the proband appears to be the only affected family member (i.e., a simplex case), molecular genetic testing is recommended for the parents of the proband to evaluate their genetic status and inform recurrence risk assessment. Note: A proband may appear to be the only affected family member because of failure to recognize the disorder in family members, reduced penetrance, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent. Therefore, de novo occurrence of a WT1 pathogenic variant cannot be confirmed unless molecular genetic testing has demonstrated that neither parent is heterozygous for the WT1 pathogenic variant.
• If the pathogenic variant identified in the proband is not identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:
  • The proband has a de novo pathogenic variant.
  • The proband inherited a pathogenic variant from a parent with gonadal (or somatic and gonadal) mosaicism* [Beltcheva et al 2016]. Note: Testing of parental leukocyte DNA may not detect all instances of somatic mosaicism and will not detect a pathogenic variant that is present in the germ (gonadal) cells only.
    * If the parent is the individual in whom the WT1 pathogenic variant first occurred, the parent may have somatic mosaicism for the variant and may be mildly/minimally affected or asymptomatic [Beltcheva et al 2016].

Sibs of a proband. The risk to the sibs of the proband depends on the clinical/genetic status of the proband's parents:

• If a parent of the proband is affected and/or is known to have the WT1 pathogenic variant identified in the proband, the risk to the sibs of inheriting the WT1 pathogenic variant is 50%. Although a sib who inherits a pathogenic variant is likely to have clinical manifestations of WT1 disorder, the phenotype in a heterozygous sib cannot be reliably predicted because both intrafamilial clinical variability and reduced penetrance are observed in WT1 disorder (see Penetrance).
• If the WT1 pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population because of the possibility of parental gonadal mosaicism [Beltcheva et al 2016].
• If the parents have not been tested for the WT1 pathogenic variant but are clinically unaffected, the risk to the sibs of a proband appears to be low. However, sibs of a proband with clinically unaffected parents are still presumed to be at increased risk for WT1 disorder because of the possibility of reduced penetrance in a heterozygous parent and the possibility of parental gonadal mosaicism.

Offspring of a proband. Each child of an individual with WT1 disorder has a 50% chance of inheriting the WT1 pathogenic variant. Note: Most individuals with a disorder of testicular development are infertile.

Other family members. The risk to other family members depends on the status of the proband's parents: if a parent has the WT1 pathogenic variant, the parent's family members may be at risk.

Related Genetic Counseling Issues

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

Family planning

• The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
• It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

Prenatal Testing and Preimplantation Genetic Testing

Once the WT1 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.

Molecular Pathogenesis

WT1 encodes the regulatory protein Wilms tumor protein (WT1), comprising a proline- and glutamine-rich interaction domain and four zinc fingers (exons 7-10), which determine the sequence specificity of this critical transcription factor [Wang et al 2018, Nagano & Nozu 2025]. Expression of WT1 occurs for the most part in kidney progenitors and podocytes; in the urogenital ridge; and in gonadal progenitors [Wilm & Muñoz-Chapuli 2016]. More than 30 WT1 isoforms are derived from alternative splicing as well as alternative translation start sites and RNA editing; their relative ratios regulate particular processes of urogenital differentiation.

WT1 is a major transcription factor involved in cell differentiation and survival in the developing kidney, urinary tract, and gonads. WT1 regulates the expression of numerous target genes, including many genes encoding proteins that localize to the slit diaphragm of the glomeruli, such as nephrin and podocin. WT1 controls the polarity of podocytes, cytoskeleton arrangement, and the cell-matrix adhesion of podocytes. It has a tumor suppressor as well as an oncogenic role in tumor formation [Dong et al 2015].

Mechanism of disease causation

• Dominant-negative mechanism. WT1 disorder is caused by a dominant-negative mechanism. For example, missense, nonsense, and frameshift variants that affect the zinc finger region may result in the loss, reduction, or altered specificity of WT1 isoforms to bind target DNAs. The numerous WT1 isoforms, derived from alternative splicing, alternative translation start sites, and RNA editing, likely have varying effects in different tissues during development. For example, two common pathogenic variants with intron splice site nucleotide changes (see Table 6) alter the ratio of alternative transcripts. Physiologically, an alternative donor splice site in intron 9 of WT1 results in the addition of three amino acid residues – lysine (K), threonine (T), and serine (S), referred to as the KTS splice variant – between the third and fourth zinc finger domains. Disruption of this splice site due to single-nucleotide variants at positions +4 or +5 of intron 9 alters the ratio of the WT1 isoforms with and without the KTS insert (+KTS and −KTS, respectively). Affected individuals have significantly fewer +KTS splice variants, resulting in a decreased ratio of +KTS:−KTS isoforms, a regulatory factor involved in proper testicular development in 46,XY individuals.
• Tumor suppressor mechanism. Consistent with the Knudson two-hit model of tumorigenesis and previous observations, children with a germline loss-of-function WT1 variant are at very high risk for Wilms tumor (see Wilms Tumor Predisposition). See also Cancer and Benign Tumors.

WT1-specific laboratory technical considerations. Because of high GC (guanine and cytosine) content, the sequencing of exon 1 of WT1 is problematic. The numerous transcripts and their isoforms resulting from alternative splicing and translation start sites result in a single variant having many HGVS-approved names depending on the reference sequence. As there is no consensus in the literature or databases as to the "canonic" protein sequence, care must be taken when interpreting numbers of residues. In this chapter, amino acid positions are given according to NP_077742.3 (see Table 6).

Notable WT1 variants. Variants discussed in Clinical Characteristics, Genotype-Phenotype Correlations include the following:

• Missense variants affecting nucleotides coding for DNA-binding helices of zinc fingers 2 and 3 (residues: 439-454[RSDQLKRHQRRHTGVK] from exon 8 and 467-474[RSDHLKTH] from exon 9 [Nagano et al 2021]; reference sequence NP_077742.3)
• Certain splice site pathogenic single-nucleotide variants in the splice donor site of intron 9 that change the ratio of +KTS:−KTS isoforms (see Table 6) [Tsuji et al 2021]

Note: Originally, WT1 pathogenic variants were subclassified as exon variants (presumably Denys-Drash syndrome-type) and KTS intron variants (presumably Frasier syndrome-type) (see Nomenclature).

A few recurrent pathogenic variants, both exon and intron, have been identified (see Table 6).

Cancer and Benign Tumors

Somatic WT1 variants have been described in sporadic Wilms tumors as well as in a significant proportion of other cancers, in particular desmoplastic small round cell tumor of childhood and leukemia.

Loss-of-function WT1 variants are reported in about 15% of sporadic Wilms tumors.

In hematologic malignancies, somatic WT1 variants are noted in about 6% to 15% of de novo acute myeloid leukemia (AML) and are associated with poor prognosis.

The EWS-WT1 gene fusion is pathognomonic for desmoplastic small round cell tumor, an extremely rare aggressive soft tissue malignancy [Charlton & Pritchard-Jones 2016].

Author Notes

Beata S Lipska-Ziętkiewicz is the genetic coordinator at PodoNet (www.escapenet.eu/researchers/beata-lipska-zietkiewicz), one of the largest international registries of steroid-resistant nephrotic syndrome. She is a member of the Molecular Diagnostics Task Force for the European Rare Kidney Disease Reference Network (ErkNet; www.erknet.org).

Revision History

• 15 May 2025 (sw) Comprehensive update posted live
• 30 April 2020 (bp) Review posted live
• 2 October 2019 (blz) Original submission

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