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WAGR Syndrome Follow-up

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

Further Outpatient Care

Oncologic follow-up care: After initial evaluation and treatment, the long-range plan for children with Wilms tumor, aniridia, GU abnormalities, and mental retardation (WAGR) syndrome is regular follow-up. Note the following:

  • Abdominal ultrasonography should be performed every 3 months to examine the kidneys for the development of a Wilms tumor. The age at which these tests may be discontinued has not been established, although the general recommendation is to continue until the patient is aged 7 years.
  • In a report of a cohort of 61 patients with WAGR syndrome, the oldest patient in whom Wilms tumor developed was aged 7 years 3 months.[16] Of the patients in whom tumors ultimately developed, 98% received the diagnosis before their seventh birthday. Reports of patients with AGR syndrome who develop Wilms tumor later in life, one of whom developed Wilms at age 25 years, suggest that further follow-up, by either physical examination or ultrasonography, may be recommended for older patients.

Ophthalmologic follow-up care: Patients with WAGR syndrome require routine ophthalmologic follow-up, both to evaluate and maximize their vision and to detect glaucoma or cataracts.

Nephrologic follow-up care: Patients with WAGR syndrome appear to have an increased risk of renal failure, which develops over many years. Note the following:

  • Long-term follow-up should include a regular evaluation of renal function with urinalysis and assessment of blood pressure and BUN and creatinine levels. Renal ultrasonography should be considered if abnormalities are suspected. Rare WAGR patients may develop focal segmental glomerular sclerosis with or without the development of Wilms tumor.
  • Patients with Denys-Drash and Frasier syndromes have long been known to be at an increased risk for renal failure.
  • The NWTS found that the incidence of renal failure is 38% in patients with aniridia and Wilms tumor, compared with only 21 cases in 5358 patients without characteristic congenital GU abnormalities.[6]
  • In one cohort of 54 patients with WAGR syndrome, 14 patients had some level of renal failure.[17] This suggests that renal failure is not only related to the loss of kidney tissue in these patients. Some of them had focal segmental glomerular sclerosis (FSGS) unrelated to the development of Wilms tumor. A recent study reported small glomeruli in patients with WAGR syndrome, suggesting that, in some cases, a structural explanation for the eventual appearance of end-stage renal disease is noted.[18]
  • The underlying reason for renal dysfunction may be multifactorial.
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Prognosis

Patients with WAGR syndrome have an excellent prognosis for long-term survival. Morbidity and mortality associated with late development of renal failure may be more significant than Wilms tumor.

Life-limiting abnormalities include GU anomalies in the first year of life. Lifelong disabilities may include vision loss and mental retardation.

In the approximately 30% of patients with AGR syndrome in whom a Wilms tumor develops, the prognosis is related to the histologic features and the stage of the tumor.

Early detection seems to improve the outcome.

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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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