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WAGR Syndrome Workup

  • Author: Steven K Bergstrom, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
 
Updated: Dec 02, 2015
 

Laboratory Studies

Renal function is rarely affected by nephroblastomatosis alone. GU abnormalities may lead to reduced renal function early in life.

Consider the following laboratory studies:

  • BUN and/or creatinine levels should be assessed in patients with Wilms tumor, aniridia, GU abnormalities, and mental retardation (WAGR) syndrome.
  • Findings of protein in the urine should alert the clinician to the possibility of Denys-Drash or Frasier syndromes, which are associated with declining renal function. Blood may be present in the urine when patients present with a Wilms tumor.
  • A CBC count with a platelet count may demonstrate anemia due to blood loss secondary to an enlarging renal mass.
  • Serum calcium levels should be measured.
  • Cytogenetic testing should be performed to confirm the diagnosis. Standard high-resolution chromosome studies may not be able to detect deletions in WT1. The addition of molecular cytogenetic fluorescence in situ hybridization techniques may define the extent of the deletion.
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Imaging Studies

Ultrasonography

Renal ultrasonography is the study of choice to confirm the diagnosis of renal pathology in the neonatal period. Note the following:

  • Enlargement of the kidneys usually suggests nephroblastomatosis. The appearance of both kidneys should be documented.
  • Some (internal) GU abnormalities are usually best documented using ultrasonography, although additional imaging tests may be required.[14]
  • A follow-up examination of the kidneys should be performed every 3 months until the patient is aged 7 years. Physical examinations should be performed every 6 months until the patient's growth is complete. Baseline CT scanning may be indicated at the time of the initial diagnosis.
  • The presence of an enlarging renal mass suggests the development of a Wilms tumor.
  • Evaluation of the renal vein and inferior vena cava for the presence of tumor thrombi is important for staging, and the study is usually accomplished using renal ultrasonography and/or Doppler imaging.

Radiography

Chest radiography becomes important in the staging workup once Wilms tumor is diagnosed.

Computed Tomography

CT scanning of the chest and abdomen may provide further information about the location and stage of the tumor.

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Procedures

The role of a renal biopsy at the time of diagnosis of WAGR syndrome in the neonatal period is controversial. Transcutaneous renal biopsy has no role in the diagnosis of a Wilms tumor.

The presence of nephrogenic rests can be demonstrated histologically, but the risk of losing renal function as a result of the procedure may outweigh the need to confirm the diagnosis in a patient with AGR syndrome.

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Histologic Findings

Biopsy findings of kidneys that contain nephrogenic rests or nephroblastomatosis reveal nests of developmentally immature renal parenchyma. Although these rests may be stable over a long period, they generally (1) die and produce a hyalinized remnant, (2) mature into normal renal parenchyma, or (3) produce a Wilms tumor.

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Contributor Information and Disclosures
Author

Steven K Bergstrom, MD Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Timothy P Cripe, MD, PhD, FAAP Chief, Division of Hematology/Oncology/BMT, Gordon Teter Endowed Chair in Pediatric Cancer, Nationwide Children's Hospital; Professor of Pediatrics, Ohio State University College of Medicine

Timothy P Cripe, MD, PhD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Association for Cancer Research, American Pediatric Society, American Society of Gene and Cell Therapy, American Society of Pediatric Hematology/Oncology, Connective Tissue Oncology Society, Society for Pediatric Research, Children's Oncology Group

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Stephan A Grupp, MD, PhD Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania School of Medicine

Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, Society for Pediatric Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

References
  1. Al-Hussain T, Ali A, Akhtar M. Wilms tumor: an update. Adv Anat Pathol. 2014 May. 21 (3):166-73. [Medline].

  2. Yamamoto T, Togawa M, Shimada S, Sangu N, Shimojima K, Okamoto N. Narrowing of the responsible region for severe developmental delay and autistic behaviors in WAGR syndrome down to 1.6 Mb including PAX6, WT1, and PRRG4. Am J Med Genet A. 2014 Mar. 164A (3):634-8. [Medline].

  3. Han JC, Thurm A, Golden Williams C, et al. Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome. Cortex. 2013 Feb 19. [Medline]. [Full Text].

  4. Han JC, Liu QR, Jones M, et al. Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N Engl J Med. Aug 2008. 359:918-927. [Medline].

  5. Rodriguez-Lopez R, Perez JM, Balsera AM, et al. The modifier effect of the BDNF gene in the phenotype of the WAGRO syndrome. Gene. 2013 Mar 10. 516(2):285-90. [Medline].

  6. D'Angio GJ, Breslow N, Beckwith JB, et al. Treatment of Wilms' tumor. Results of the Third National Wilms' Tumor Study. Cancer. 1989 Jul 15. 64(2):349-60. [Medline].

  7. Breslow N, Olshan A Beckwith JB. Epidemiology of Wilms tumor. Med Ped Oncol. 1993. 21:172-181.

  8. Robinson DO, Howarth RJ, Williamson KA, van Hyningen V, Beal SJ, Crolla JA. Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia. Am J Med Genet A. Mar 2008. 164A:558-569. [Medline].

  9. Termine C, Parigi G, Rossi M, Romano P, Balotin U. WAGR syndrome: is the 'R' always justified?. Clin Dysmorphol. Jan 2007. 16:69-70. [Medline].

  10. Knudson AG, Strong LC. Mutation and cancer: a model for Wilms tumor of the kidney. J Natl Cancer Inst. Feb 1972. 48:313-324.

  11. Call KM, Glaser T, Ito CY. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms tumor locus. Cell. Feb 1990. 60:509-520.

  12. Ton CCT, Hirvonen H, Miwa H. Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell. 1991. 67:1059-1074.

  13. Haber DA, Oshn RL, Buckler AJ. Alternative splicing and alternative structure of the Wilms tumor gene WT1. Proc Natl Acad Sci USA. 1991. 88:9618-9622.

  14. Tezcan B, Rich P, Bhide A. Prenatal Diagnosis of WAGR Syndrome. Case Rep Obstet Gynecol. 2015. 2015:928585. [Medline].

  15. Hamilton TE, Ritchey ML, Haase GM,et al. The management of synchronous bilateral wilms tumor: a report from the national wilms tumor study group. Ann Surg. 2011 May. 253(5):1004-10. [Medline].

  16. Beckwith JB. Precursor lesions of Wilms tumor: clinical and biological impications. Med Pediatr Oncol. 1993. 21:158-168.

  17. Fischbach BV, Trout KL, Lewis J. WAGR syndrome: A clinical review of 54 cases. Pediatrics. Oct 2005. 116:984-988.

  18. Dahan K, Kamal M, Noel LH, et al. Small glomeruli in WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies and mental retardation) syndrome. Am J Kidney Dis. June 2007. 49:522-527.

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Subjects were categorized as BDNF haploinsufficient by comparative genomic hybridization. Subject A has a large deletion on chromosome 11 that removes one copy of the BDNF gene. Subject B has a smaller deletion that does not remove BDNF.
Aniridia. Note the almost complete absence of the iris.
 
 
 
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