U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

WT1 Disorder

, MD, PhD.

Author Information and Affiliations

Initial Posting: ; Last Update: May 15, 2025.

Estimated reading time: 32 minutes

Summary

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.

Diagnosis

Formal diagnostic criteria for WT1 disorder have not been established.

Note: This chapter on WT1 disorder excludes WAGR syndrome (Wilms tumor-aniridia-genital anomalies-range of developmental delays), caused by a contiguous gene deletion of PAX6 and WT1 (see PAX6-Related Aniridia).

Suggestive Findings

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

Clinical Findings

Steroid-resistant nephrotic syndrome. A progressive glomerulopathy that does not respond to standard steroid therapy; see Trautmann et al [2020] and Boyer et al [2021] for diagnostic clinical practice guidelines.

  • Onset from infancy to the second or third decade of life
  • Manifestations in the order in which they typically (but not invariably) appear:
    • Persistent proteinuria, defined as any one of the following lasting more than three months: 24-hour protein excretion >100 mg/m2/day OR urine protein-to-creatinine ratio ≥0.2 mg/mg (≥0.5 mg/mg if age <2 yrs) OR urine protein-to-creatinine ratio >20 mg/mmol (>50 mg/mmol if age <2 yrs) [Hogg et al 2003]
    • Steroid-resistant nephrotic syndrome (SRNS), defined as nephrotic syndrome (defined as hypoalbuminemia, edema, and hyperlipidemia) that does not respond to standard steroid therapy (see also Genetic Steroid-Resistant Nephrotic Syndrome Overview). Note: "Congenital nephrotic syndrome" is nephrotic syndrome manifesting in the first three months of life.
    • Chronic kidney disease (CKD), defined as glomerular filtration rate <60 mL/min/1.73 m2) [Hogg et al 2003]

Disorders of testicular development (See Nonsyndromic Disorders of Testicular Development Overview.)

  • 46,XY disorder of sex development (46,XY DSD)
    • External genitalia that can range over the following spectrum:
      • Ambiguous with mild-to-severe penoscrotal hypospadias with or without chordee
      • Microphallus
      • Abnormalities of scrotal formation
      • Normal-appearing female
    • Müllerian structures that on ultrasound (US) examination, MRI, and/or laparoscopy can range over the following spectrum:
      • Absent
      • Fully developed uterus and fallopian tubes
    • Gonadal findings as determined by a combination of physical examination, imaging, and hormonal testing (and on occasion histologic examination) that can range over the following spectrum:
      • Normal testis
      • Dysgenetic testis (decreased size and number of seminiferous tubules, reduced number or absence of germ cells, peritubular fibrosis, and hyperplasia of Leydig cells)
      • Streak gonad
  • 46,XY complete gonadal dysgenesis (46,XY CGD)
    • External genitalia. Normal female
    • Müllerian structures. Uterus and fallopian tubes present
    • Gonadal findings. Streak gonads or dysgenetic testes

Note: 46,XX individuals with WT1 disorder may have abnormalities of the müllerian structures such as bicornuate uterus and typically do not have a disorder of gonadal development. However, two individuals with 46,XX complete gonadal dysgenesis have been reported [Ahn et al 2017, Roca et al 2019], and seven individuals with 46,XX testicular DSD or ovotesticular DSD have been reported [Eozenou et al 2020].

Early gonadal insufficiency. A recent study of 80 individuals with WT1 pathogenic variants reported early gonadal insufficiency of variable severity with potential impact on puberty and fertility in the majority of individuals (all karyotypes and genotypes) irrespective of the onset of renal insufficiency [Carré Lecoindre et al 2024].

Wilms tumor, especially in children with:

  • Early-onset Wilms tumor (i.e., median age 1.3-1.6 years vs median age of 3 years in children without a WT1 pathogenic variant) OR
  • Bilateral Wilms tumors

Congenital anomalies of the kidney and urinary tract (CAKUT) including:

  • Duplex kidney; horseshoe kidney; kidney malrotation
  • Vesicoureteral reflux; ureteropelvic junction stenosis; urogenital sinus

Gonadoblastoma (germ cell tumor). Most commonly in 46,XY individuals with a disorder of testicular development

Other. Diaphragmatic hernia

Supportive Laboratory Findings

Normal 46,XX karyotype or normal 46,XY karyotype determined by either:

  • Chromosome analysis with FISH to determine the integrity of SRY, or
  • Chromosomal microarray analysis

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).

Option 1

Single-gene testing. Sequence analysis of WT1 detects small missense, nonsense, and splice site variants and intragenic deletions/insertions. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications. Note: Some laboratories may choose to sequence exons 8 and 9 and their intronic junctions first because more than 90% of pathogenic variants are in that region [Lipska et al 2014].

A multigene panel that includes WT1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition while limiting identification of pathogenic variants and variants of uncertain significance in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.

For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

Option 2

Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used; genome sequencing is also possible.

For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in WT1 Disorder

Gene 1MethodProportion of Pathogenic Variants 2 Identified by Method
WT1 Sequence analysis 3>90% 4
Gene-targeted deletion/duplication analysis 5<10% 6
1.
2.

See Molecular Genetics for information on variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.
5.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.

6.

Several exon and multiexon deletions have been reported [Finken et al 2015, van Peer et al 2024].

Clinical Characteristics

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].

Table 2.

WT1 Disorder: Frequency of Select Features

Feature% of Persons w/FeatureComment
Glomer-
ulopathy
Persistent
proteinuria
>95%Renal hallmark of WT1 disorder; degree may vary over time
SRNS80%Criteria for diagnosis of SRNS 1 may not be met initially.
CNS15%Nephrotic syndrome within 1st 3 mos of life
External genitalia Müllerian structures Gonadal findings
Disorder of
testicular
development
46,XX DSD or CGDSee footnote 2.Range: microphallus, hypospadias & cryptorchidism, ambiguous, normal-appearing femaleRange: absent to normal uterus & fallopian tubesRange: ovotestis, dysgenetic testis, streak gonads, hypertrophic ovaries, or normal ovaries
46,XY DSD63%-79% of 46,XY individuals 3Range: microphallus, hypospadias & cryptorchidism, ambiguous, normal-appearing femaleRange: absent to normal uterus & fallopian tubesRange: normal testis, ovotestis, dysgenetic testis, streak gonad
46,XY CGD18%-33% of 46,XY individuals 3Normal femaleUterus & fallopian tubes presentStreak gonads or dysgenetic testes
Early gonadal insufficiency 67% at 12.6 yrs (83% at 16.2 yrs) 4
  • Spontaneous puberty in 94% of 46,XX & 60% of 46,XY persons
  • ↑ FSH & LH; ↓ AMH or inhibin B plasma levels in majority of persons
Wilms tumor 38%-60% 3
  • Median age at diagnosis: 1.3-1.6 yrs
  • Significant fraction is bilateral synchronous &/or metachronous
CAKUT ~11% 3
  • Kidney: duplex; horseshoe; malrotation
  • Urinary tract: vesicoureteral reflux; ureteropelvic junction stenosis; urinary sinus
Gonadoblastoma 5%

AMH = anti-műllerian hormone; CAKUT = congenital anomalies of the kidney and urinary tract; CGD = complete gonadal dysgenesis; CNS = congenital nephrotic syndrome; DSD = disorder of sex development; FSH = follicle-stimulating hormone; LH = luteinizing hormone; SRNS = steroid-resistant nephrotic syndrome

1.

Nephrotic syndrome (proteinuria, hypoalbuminemia, edema, and hyperlipidemia) that does not respond to standard steroid therapy

2.

Two instances of 46,XX complete gonadal dysgenesis have been reported [Ahn et al 2017, Roca et al 2019]. Seven 46,XX individuals with a WT1 pathogenic variant had testicular DSD or ovotesticular DSD [Eozenou et al 2020].

3.
4.

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.

Differential Diagnosis

For the differential diagnosis of:

Management

See Trautmann et al [2020] and Boyer et al [2021] for clinical practice recommendations for the management of children with steroid-resistant nephrotic syndrome.

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).

Table 4.

WT1 Disorder: Treatment of Manifestations

Manifestation/ConcernTreatmentConsiderations/Other
Glomer-
ulopathy
Persistent
proteinuria
Consider RAAS inhibition: ACE inhibitor, AT1 receptor blocker. 1
  • Avoid immunosuppressants, which are ineffective & potentially toxic. 1
  • Nephropathy does not recur post kidney transplantation. 2
SRNS
CKD
CNS
Disorder of testicular development & 46,XX gonadal dysgenesis See Nonsyndromic Disorders of Testicular Development Overview.Mgmt is often by multidisciplinary team incl clinical geneticist, endocrinologist, urologist, & psychologist.
Wilms tumor Standard oncology protocols; surgery w/nephron-sparing approach whenever applicableBilateral prophylactic nephrectomy after reaching end-stage kidney failure (i.e., at time of kidney transplantation or placement of peritoneal dialysis catheter) 3
CAKUT Urologic intervention may be applicable.Per treating nephrologist &/or urologist
Gonadoblastoma Gonadectomy per DSD team in those w/a disorder of testicular developmentNo consensus re timing of surgery
Diaphragmatic hernia Per treating surgeonRepair to be performed prior to start of peritoneal dialysis

ACE = angiotensin-converting enzyme; AT1 = angiotensin II type 1; CAKUT = congenital anomalies of the kidney and urinary tract; CKD = chronic kidney disease; CNS = congenital nephrotic syndrome; DSD = disorders of sex development; RAAS = renin-angiotensin-aldosterone system; SRNS = steroid-resistant nephrotic syndrome

1.
2.

For a child to be eligible for kidney transplantation, most centers require that children weigh 10 kg and/or be at least one year post completion of treatment for Wilms tumor.

3.

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.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of 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; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

WT1 disorder is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

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.

Resources

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.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

WT1 Disorder: Genes and Databases

GeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
WT1 11p13 Wilms tumor protein WT1 database WT1 WT1

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for WT1 Disorder (View All in OMIM)

136680FRASIER SYNDROME
194070WILMS TUMOR 1; WT1
194080DENYS-DRASH SYNDROME; DDS
256370NEPHROTIC SYNDROME, TYPE 4; NPHS4
607102WT1 TRANSCRIPTION FACTOR; WT1
608978MEACHAM SYNDROME

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).

Table 6.

WT1 Pathogenic Variants Referenced in This GeneReview

Reference SequencesDNA Nucleotide ChangePredicted Protein ChangeComment [Reference]
NM_024426​.6
NP_077742​.3
c.1399C>T 1p.Arg467Trp 1Most common pathogenic variant
NM_024426​.6 c.1447+4C>T 2--Common pathogenic variant; typical for 46,XY CGD [Barbaux et al 1997]
c.1447+5G>A 3--

CGD = complete gonadal dysgenesis

Variants listed in the table have been provided by the author. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1.

Alternate variant designations exist (e.g., c.1384C>T, 1180C>T, p. Arg462Trp, Arg394Trp). Originally reported as p.Arg394Trp [Pelletier et al 1991]. See ClinVar and Ensembl sites for rs121907900.

2.

Alternate variant designations exist (e.g., 1432+4C>T, IVS9+4C>T). See ClinVar and Ensembl for rs587776577.

3.

Alternate variant designations using other reference sequences exist (e.g., 1432+5G>A, IVS9+5G>A). See ClinVar and Ensembl for rs587776576.

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].

Chapter Notes

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

References

Literature Cited

  • Ahn YH, Park EJ, Kang HG, Kim SH, Cho HY, Shin JI, Lee JH, Park YS, Kim KS, Ha IS, Cheong H. Genotype-phenotype analysis of pediatric patients with WT1 glomerulopathy. Pediatr Nephrol. 2017;32:81-9. [PubMed: 27300205]
  • Anderson E, Aldridge M, Turner R, Harraway J, McManus S, Stewart A, Borzi P, Trnka P, Burke J, Coman D. WT1 complete gonadal dysgenesis with membranoproliferative glomerulonephritis: case series and literature review. Pediatr Nephrol. 2022;37:2369-74 [PMC free article: PMC9395477] [PubMed: 35211794]
  • Barbaux S, Niaudet P, Gubler MC, Grünfeld JP, Jaubert F, Kuttenn F, Fékété CN, Souleyreau-Therville N, Thibaud E, Fellous M, McElreavey K. Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet. 1997;17:467-70. [PubMed: 9398852]
  • Beltcheva O, Boueva A, Tzveova R, Roussinov D, Marinova S, Kaneva R, Mitev V. Steroid-resistant nephrotic syndrome caused by novel WT1 mutation inherited from a mosaic parent. Ren Fail. 2016;38:290-3. [PubMed: 26627896]
  • Boyer O, Dorval G, Servais A. Hereditary podocytopathies in adults: the next generation. Kidney Dis (Basel). 2017;3:50-56. [PMC free article: PMC5566765] [PubMed: 28868292]
  • Boyer O, Schaefer F, Haffner D, Bockenhauer D, Hölttä T, Bérody S, Webb H, Heselden M, Lipska-Zie Tkiewicz BS, Ozaltin F, Levtchenko E, Vivarelli M. Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group. Nat Rev Nephrol. 2021;17:277-89. [PMC free article: PMC8128706] [PubMed: 33514942]
  • Carré Lecoindre M, Mallet D, Dossier C, Glenisson M, Grapin M, Brac de la Perriere A, Chakhtoura Z, Bouvattier C, Houang M, Pienkowski C, Zaegel N, Rayneau R, Blanc T, Martinerie L. Gonadal function throughout life in XX and XY patients with a germline WT1 variant - lessons from a cohort of 80 patients. J Endocr Soc. 2024;8(Suppl 1):bvae163.1692. [Abstract only]
  • Charlton J, Pritchard-Jones K. WT1 mutation in childhood cancer. In: Hastie N, eds. The Wilms' Tumor (WT1) Gene. Methods in Molecular Biology vol 1467. New York, NY: Humana Press; 2016:1-14. [PubMed: 27417955]
  • Chernin G, Vega-Warner V, Schoeb DS, Heeringa SF, Ovunc B, Saisawat P, Cleper R, Ozaltin F, Hildebrandt F, et al. Genotype/phenotype correlation in nephrotic syndrome caused by WT1 mutations. Clin J Am Soc Nephrol. 2010;5:1655-62. [PMC free article: PMC2974408] [PubMed: 20595692]
  • Denamur E, Bocquet N, Baudouin V, Da Silva F, Veitia R, Peuchmaur M, Elion J, Gubler MC, Fellous M, Niaudet P, Loirat C. WT1 splice-site mutations are rarely associated with primary steroid-resistant focal and segmental glomerulosclerosis. Kidney Int. 2000;57:1868-72. [PubMed: 10792605]
  • Dong L, Pietsch S, Englert C. Towards an understanding of kidney diseases associated with WT1 mutations. Kidney Int. 2015;88:684-90. [PMC free article: PMC4687464] [PubMed: 26154924]
  • Duffy KA, Trout KL, Gunckle JM, Krantz SM, Morris J, Kalish JM. Results from the WAGR Syndrome Patient Registry: characterization of WAGR spectrum and recommendations for care management. Front Pediatr. 2021;9:733018. [PMC free article: PMC8712693] [PubMed: 34970513]
  • Eozenou C, Gonen N, Touzon MS, Jorgensen A, Yatsenko SA, Fusee L, Kamel AK, Gellen B, Guercio G, Singh P, Witchel S, Berman AJ, Mainpal R, Totonchi M, Mohseni Meybodi A, Askari M, Merel-Chali T, Bignon-Topalovic J, Migale R, Costanzo M, Marino R, Ramirez, P, Perez Garrido N, Berensztein E, Mekkawy MK, Schimenti JC, Bertalan R, Mazen I, McElreavey K Belgorosky A, Lovell-Badge R, Rajkovic A, Bashamboo A. Testis formation in XX individuals resulting from novel pathogenic variants in Wilms’ tumor 1 (WT1) gene. Proc Natl Acad Sci U S A. 2020;117:13680-8. [PMC free article: PMC7306989] [PubMed: 32493750]
  • Fencl F, Malina M, Stará V, Zieg J, Mixová D, Seeman T, Bláhová K. Discordant expression of a new WT1 gene mutation in a family with monozygotic twins presenting with congenital nephrotic syndrome. Eur J Pediatr. 2012;171:121-4. [PubMed: 21614510]
  • Finken MJJ, Hendriks YMC, van der Voorn JP, Veening MA, Lombardi MA, Rotteveel J. WT1 deletion leading to severe 46,XY gonadal dysgenesis, Wilms tumor and gonadoblastoma: case report. Horm Res Paediatr. 2015;83:211-6. [PubMed: 25613702]
  • Gariépy-Assal L, Gilbert RD, Žiaugra A, Foster BJ. Management of Denys-Drash syndrome: a case series based on an international survey. Clin Nephrol Case Stud. 2018;6:36-44. [PMC free article: PMC6236398] [PubMed: 30450273]
  • Glénisson M, Grapin M, Blanc T, Preka E, Hogan J, Aurelle M, Roussey G, Mouche A, Rousset-Rouviere C, Novo R, Faudeux C, Fila M, Vrillon I, Cloarec S, Simon T, Harambat J, Martinez Casado E, Rod J, Carre Lecoindre M, Heidet L, Boyer O, Garcelon N, Kachmar J, Dorval G, Sarnacki S. Genotype-phenotype correlations in Denys-Drash syndrome in children. Kidney Int Rep, 2025: 10(4):1205-1212 [PMC free article: PMC12034853] [PubMed: 40303223]
  • Guaragna MS, Lutaif AC, Piveta CS, Belangero VM, Maciel-Guerra AT, Guerra G Jr, De Mello MP. Two distinct WT1 mutations identified in patients and relatives with isolated nephrotic proteinuria. Biochem Biophys Res Commun. 2013;441:371-6. [PubMed: 24161391]
  • Hol JA, Jewell R, Chowdhury T, Duncan C, Nakata K, Oue T, Gauthier-Villars M, Littooij AS, Kaneko Y, Graf N, Bourdeaut F, van den Heuvel-Eibrink MM, Pritchard-Jones K, Maher ER, Kratz CP, Jongmans MCJ. Wilms tumour surveillance in at-risk children: literature review and recommendations from the SIOP-Europe Host Genome Working Group and SIOP Renal Tumour Study Group. Eur J Cancer. 2021;153:51–63. [PubMed: 34134020]
  • Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz AT, Eknoyan G, Levey AS. National Kidney Foundation's Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics. 2003;111:1416-21. [PubMed: 12777562]
  • Kaneko Y, Okita H, Haruta M, Arai Y, Oue T, Tanaka Y, Horie H, Hinotsu S, Koshinaga T, Yoneda A, Ohtsuka Y, Taguchi T, Fukuzawa M. 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;112:1121-33. [PMC free article: PMC4366886] [PubMed: 25688735]
  • Kirino S, Yogi A, Adachi E, Nakatani H, Gau M, Iemura R, Yamano H, Kanamori T, Mori T, Sohara E, Uchida S, Okamoto K, Udagawa T, Takasawa K, Morio T, Kashimada K. Phenotypic variation in 46,XX disorders of sex development due to the fourth zinc finger domain variant of WT1: a familial case report. Sex Dev. 2023;17:51-55. [PubMed: 36796343]
  • Kitsiou-Tzeli S, Deligiorgi M, Malaktari-Skarantavou S, Vlachopoulos C, Megremis S, Fylaktou I, Traeger-Synodinos J, Kanaka-Gantenbein C, Stefanadis C, Kanavakis E. Sertoli cell tumor and gonadoblastoma in an untreated 29-year-old 46,XY phenotypic male with Frasier syndrome carrying a WT1 IVS9+4C>T mutation. Hormones (Athens). 2012;11:361-7. [PubMed: 22908070]
  • Lehnhardt A, Karnatz C, Ahlenstiel-Grunow T, Benz K, Benz MR, Budde K, Büscher AK, Fehr T, Feldkötter M, Graf N, Höcker B, Jungraithmayr T, Klaus G, Koehler B, Konrad M, Kranz B, Montoya CR, Müller D, Neuhaus TJ, Oh J, Pape L, Pohl M, Royer-Pokora B, Querfeld U, Schneppenheim R, Staude H, Spartà G, Timmermann K, Wilkening F, Wygoda S, Bergmann C, Kemper MJ. Clinical and molecular characterization of patients with heterozygous mutations in Wilms tumor suppressor gene 1. Clin J Am Soc Nephrol. 2015;10:825-31. [PMC free article: PMC4422247] [PubMed: 25818337]
  • Lipska BS, Ranchin B, Iatropoulos P, Gellermann J, Melk A, Ozaltin F, Caridi G, Seeman T, Tory K, Jankauskiene A, Zurowska A, Szczepanska M, Wasilewska A, Harambat J, Trautmann A, Peco-Antic A, Borzecka H, Moczulska A, Saeed B, Bogdanovic R, Kalyoncu M, Simkova E, Erdogan O, Vrljicak K, Teixeira A, Azocar M, Schaefer F, et al. Genotype-phenotype associations in WT1 glomerulopathy. Kidney Int. 2014;85:1169-78. [PubMed: 24402088]
  • Mussa A, Duffy KA, Carli D, Griff JR, Fagiano R, Kupa J, Brodeur GM, Ferrero GB, Kalish JM. The effectiveness of Wilms tumor screening in Beckwith-Wiedemann spectrum. J Cancer Res Clin Oncol. 2019;145:3115-23. [PMC free article: PMC6876630] [PubMed: 31583434]
  • Nagano C, Nozu K. A review of the genetic background in complicated WT1-related disorders. Clin Exp Nephrol. 2025;29:1–9. [PMC free article: PMC11807054] [PubMed: 39002031]
  • Nagano C, Takaoka Y, Kamei K, Hamada R, Ichikawa D, Tanaka K, Aoto Y, Ishiko S, Rossanti R, Sakakibara N, Okada E, Horinouchi T, Yamamura T, Tsuji Y, Noguchi Y, Ishimori S, Nagase H, Ninchoji T, Iijima K, Nozu K. Genotype-phenotype correlation in WT1 Exon 8 to 9 missense variants. Kidney Int Rep. 2021;6:2114. [PMC free article: PMC8343804] [PubMed: 34386660]
  • Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, Houghton DC, Junien C, Habib R, Fouser L. Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell. 1991;67:437-47. [PubMed: 1655284]
  • Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-24. [PMC free article: PMC4544753] [PubMed: 25741868]
  • Roca N, Muñoz M, Cruz A, Vilalta R, Lara E, Ariceta G. Long-term outcome in a case series of Denys-Drash syndrome. Clin Kidney J. 2019;12:836-39. [PMC free article: PMC6885669] [PubMed: 31807296]
  • Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S, Engelmann S, Vega-Warner V, Fang H, Halbritter J, Somers MJ, Tan W, Shril S, Fessi I, Lifton RP, Bockenhauer D, El-Desoky S, Kari JA, Zenker M, Kemper MJ, Mueller D, Fathy HM, Soliman NA, Hildebrandt F, et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2015;26:1279-89. [PMC free article: PMC4446877] [PubMed: 25349199]
  • Suri M, Kelehan P, O'neill D, Vadeyar S, Grant J, Ahmed SF, Tolmie J, McCann E, Lam W, Smith S, Fitzpatrick D, Hastie ND, Reardon W. WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations. Am J Med Genet A. 2007;143A:2312-20. [PubMed: 17853480]
  • Trautmann A, Schnaidt S, Lipska-Ziętkiewicz BS, Bodria M, Ozaltin F, Emma F, Anarat A, Melk A, Azocar M, Oh J, Saeed B, Gheisari A, Caliskan S, Gellermann J, Higuita LMS, Jankauskiene A, Drozdz D, Mir S, Balat A, Szczepanska M, Paripovic D, Zurowska A, Bogdanovic R, Yilmaz A, Ranchin B, Baskin E, Erdogan O, Remuzzi G, Firszt-Adamczyk A, Kuzma-Mroczkowska E, Litwin M, Murer L, Tkaczyk M, Jardim H, Wasilewska A, Printza N, Fidan K, Simkova E, Borzecka H, Staude H, Hees K, Schaefer F, et al. Long-term outcome of steroid-resistant nephrotic syndrome in children. J Am Soc Nephrol. 2017;28:3055–65. [PMC free article: PMC5619960] [PubMed: 28566477]
  • Trautmann A, Vivarelli M, Samuel S, Gipson D, Sinha A, Schaefer F, Hui NK, Boyer O, Saleem MA, Feltran L, Müller-Deile J, Becker JU, Cano F, Xu H, Lim YN, Smoyer W, Anochie I, Nakanishi K, Hodson E, Haffner D, et al. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2020;35:1529-61. [PMC free article: PMC7316686] [PubMed: 32382828]
  • Tsuji Y, Yamamura T, Nagano C, Horinouchi T, Sakakibara N, Ishiko S, Aoto Y, Rossanti R, Okada E, Tanaka E, Tsugawa K, Okamoto T, Sawai T, Araki Y, Shima Y, Nakanishi K, Nagase H, Matsuo M, Iijima K, Nozu K. Systematic review of genotype-phenotype correlations in Frasier syndrome. Kidney Int Rep. 2021;6:2585–93. [PMC free article: PMC8484119] [PubMed: 34622098]
  • van Peer SE, Kuiper RP, Hol JA, Egging S, van der Zwaag B, Lilien MR, Lombardi MP, van den Heuvel-Eibrink MM, Jongmans MCJ. Clinical characterization of a national cohort of patients with germline WT1 variants including late-onset phenotypes. Kidney Int Rep. 2024;9:3570-9. [PMC free article: PMC11652072] [PubMed: 39698353]
  • Wang D, Horton JR, Zheng Y, Blumenthal RM, Zhang X, Cheng X. Role for first zinc finger of WT1 in DNA sequence specificity: Denys-Drash syndrome-associated WT1 mutant in ZF1 enhances affinity for a subset of WT1 binding sites. Nucleic Acids Res. 2018;46:3864-77. [PMC free article: PMC5934627] [PubMed: 29294058]
  • Wilm B, Muñoz-Chapuli R. The role of WT1 in embryonic development and normal organ homeostasis. Methods Mol Biol. 2016;1467:23-39. [PubMed: 27417957]
Copyright © 1993-2025, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2025 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

Bookshelf ID: NBK556455PMID: 32352694

Views

Tests in GTR by Gene

Related information

  • OMIM
    Related OMIM records
  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed
  • Gene
    Locus Links

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...