Management of Genetic Syndromes - Chapter 53 WAGR SYNDROME
Carol L. Clericuzio, MD - Pediatric Division, University of New Mexico School of Medicine, Albuquerque, NM
Second Edition Edited by
SUZANNE B. CASSIDY, M.D. , JUDITH E. ALLANSON, M.D.
A JOHN WILEY & SONS, INC., PUBLICATION
Copyright 2005 by John Wiley & Sons, Inc., Hoboken, New Jersey.
All rights reserved. www.wiley.com
|
WAGR Syndrome: A Clinical Review of 54 Cases
"WAGR syndrome is a rare genetic disorder characterized by a de novo deletion of 11p13 and is clinically associated with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (W-A-G-R). Although the genotypic defects in WAGR syndrome have been well established, the large variety of phenotypic manifestations of the syndrome has never been reported. We report on 54 cases of WAGR syndrome to demonstrate both the classical clinical signs and nonclassical manifestations found in a large population of individuals with this disorder. An understanding of WAGR syndrome and its clinical findings can provide important insight regarding the functions of the involved genetic region. Recommendations for diagnosis, evaluation, and surveillance of patients with WAGR syndrome are also presented."
PEDIATRICS Vol. 116 No. 4 October 2005, pp. 984-988 (doi:10.1542/peds.2004-0467)
Bernard V. Fischbach, MD*, Kelly L. Trout, RN, BSN, Julia Lewis, MD*, Catherine A. Luis
and Mohammed Sika, PhD*
http://pediatrics.aappublications.org/cgi/content/full/116/4/984 |
Genital anomalies and gonadoblastoma in females with WAGR syndrome
Clericuzio, C., Trout, K., 2006.
|
Genital Abnormalities in Girls with WAGR Syndrome Are Common but Not Obvious
It is well known that many boys with WAGR syndrome have abnormalities of the genitals. These abnormalities are usually obvious at birth. Less well known is the fact that girls with WAGR syndrome can have genital abnormalities, too. Because these abnormalities are often internal, they are not so obvious and may go undiagnosed.
The reason for genital abnormalities in both boys and girls with WAGR syndrome may lie in or near the "WT1" gene. This gene is one of many that are deleted (missing) in this disorder. This gene is important, because it is involved in the development of Wilms tumor, and it is also thought to be needed for normal development of the genitals before birth.
In a report of 7 girls with WAGR syndrome, it was noted that although each was genetically female (had two X chromosomes) and all had normal-appearing external genitals, they also had various abnormalities of the uterus, vagina, and/or ovaries. 5 of the girls had absent, small, or abnormal ovaries, and one girl had gonadoblastoma (a type of cancer that is more common in abnormal ovaries). The report makes the following recommendations for all girls with WAGR syndrome:
1) Periodic screening with pelvic ultrasound or MRI
2) If abnormal ovaries are identified, the physician should consider surgical removal
3) Caregivers should be aware that menstrual irregularities are common, and can provide anticipatory guidance as needed.
from: "Genital anomalies and gonadoblastoma in females with WAGR syndrome"
Clericuzio, C., Trout, K., 2006.
|
Renal Failure in WAGR Syndrome: |
Characteristics and outcomes of children with the Wilms tumor-Aniridia syndrome: a report from the National Wilms Tumor Study Group.
Breslow NE, Norris R, Norkool PA, Kang T, Beckwith JB, Perlman EJ, Ritchey ML, Green DM, Nichols KE; National Wilms Tumor Study Group.
Department of Biostatistics, Box 357232, University of Washington, Seattle, WA 98195-7232, USA. norm@u.washington.edu
PURPOSE: Children with the rare Wilms tumor (WT)-aniridia (WAGR) syndrome have not had systematic evaluation of their clinical and pathologic features. We compared demographics, disease characteristics, and treatment outcomes in a large cohort of WT patients who did or did not have the WAGR syndrome.
PATIENTS AND METHODS: Clinical and pathology records were reviewed for 8,533 patients enrolled between 1969 and 2002 by the National Wilms Tumor Study Group.
RESULTS: Sixty-four patients (0.75%) had the WAGR syndrome. For WAGR and non-WAGR patients, respectively, the average birth weights (2.94 and 3.45 kg), median ages at diagnosis (22 and 39 months), and the percentages with bilateral disease (17% and 6%), metastatic disease (2% and 13%), favorable histology (FH) tumors (100% and 92%), and intralobar nephrogenic rests (ILNR; 77% and 22%) all differed. Survival estimates for WAGR and non-WAGR patients were 95% +/- 3% and 92% +/- 0.3% at 4 years but 48% +/- 17% and 86% +/- 1.0%, respectively, at 27 years from diagnosis. Five late deaths in WAGR patients were from end-stage renal disease (ESRD).
CONCLUSION: The excess of bilateral disease, ILNR-associated FH tumors of mixed cell type, and early ages at diagnosis in WAGR patients all fit the known phenotypic spectrum of constitutional deletion of chromosome 11p13. Despite a favorable response of their WT to treatment, WAGR patients have a high risk of ESRD as they approach adulthood. The renal pathology associated with this apparent late manifestation of WT1 deletion, and the explanation for the abnormally low birth weights in patients with del 11p13, have yet to be determined.
Publication Types:
· Research Support, U.S. Gov't, P.H.S.
PMID: 14673045 [PubMed - indexed for MEDLINE]
End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System.
· Breslow NE,
· Collins AJ,
· Ritchey ML,
· Grigoriev YA,
· Peterson SM,
· Green DM.
Department of Biostatistics, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, Washington 98195-7232, USA. norm@u.washington.edu
PURPOSE: We sought to assess accurately the full spectrum of end stage renal disease (ESRD) in Wilms tumor survivors by combining the unique resources of the National Wilms Tumor Study Group (NWTSG) and the United States Renal Data System (USRDS), and to confirm preliminary reports of an increased incidence of ESRD in patients with the Wilms tumor-aniridia syndrome (WAGR).
MATERIALS AND METHODS: ESRD was ascertained in 5,910 patients enrolled in NWTSG studies during 1969 to 1994 by record linkage to USRDS and by direct followup. Cumulative ESRD incidence was estimated accounting for intercurrent mortality.
RESULTS: Of 115 cases of ESRD 10 (9%) were ascertained by the NWTSG alone, 13 (11%) by USRDS alone and 92 (80%) by both. Cumulative incidence of ESRD at 20 years from diagnosis of unilateral Wilms tumor was 74% for 17 patients with the Denys-Drash syndrome, 36% for 37 patients with WAGR, 7% for 125 male patients with hypospadias or cryptorchidism (genitourinary [GU] anomalies) and 0.6% for 5,347 patients with none of these conditions. The incidence of ESRD after diagnosis of bilateral Wilms tumor was 50% for the Denys-Drash syndrome (6 patients), 90% for WAGR (10), 25% for GU anomaly (25) and 12% for other (409). ESRD in patients with WAGR or GU anomalies tended to occur relatively late, often during or after adolescence.
CONCLUSIONS: The risk of ESRD is remarkably low for the majority of patients with Wilms tumor. However, those with WAGR or associated GU anomalies are at higher risk and should be screened indefinitely to facilitate prospective treatment of impaired renal function.
PMID: 16217371 [PubMed - indexed for MEDLINE]
|
|
