Miller et al. (1964) first described the association of aniridia, hemihypertrophy, and other congenital anomalies with Wilms tumor. The syndrome subsequently became known as the WAGR syndrome. In addition to 'genitourinary abnormalities,' the 'G' in WAGR syndrome may ... Miller et al. (1964) first described the association of aniridia, hemihypertrophy, and other congenital anomalies with Wilms tumor. The syndrome subsequently became known as the WAGR syndrome. In addition to 'genitourinary abnormalities,' the 'G' in WAGR syndrome may refer to 'ambiguous genitalia' (Riccardi et al., 1978) or 'gonadoblastoma' (Anderson et al., 1978). Riccardi et al. (1978) observed a triad of aniridia, ambiguous genitalia, and mental retardation (AGR triad) in 3 patients with an interstitial deletion of the short arm of chromosome 11. One patient also had Wilms tumor. Among 6 cases of aniridia, Francke et al. (1978) showed that Wilms tumor was not present in all cases: monozygotic twins had aniridia and mental retardation, but only 1 had Wilms tumor, and only 1 of the other 4 patients had Wilms tumor. The deleted segment common to all was the distal half of 11p13. Anderson et al. (1978) described aniridia, cataract, and gonadoblastoma in a mentally retarded girl with an interstitial deletion of the short arm of chromosome 11. Gonadoblastoma occurs as part of the WAGR complex (Junien et al., 1980; Turleau et al., 1981). In a report that focused on the aniridia component of the WAGR syndrome, Gilgenkrantz et al. (1982) analyzed the reported cases of aniridia with interstitial del(11)p. They reported a unique observation of hypertrophic cardiomyopathy in association with aniridia and catalase (CAT; 115500) deficiency in a patient with del(11)(p15.1p12). Riccardi et al. (1982) reported a patient with Wilms tumor and iris dysplasia, not aniridia. In the UK, Shannon et al. (1982) found the incidence of aniridia in cases of Wilms tumor to be 1 in 43. A survey detected 8 living and 3 dead children with Wilms tumor and aniridia. All 8 living children had deletion of 11p13. A high incidence of bilateral Wilms tumor (36%), male sex, early presentation, and advanced maternal age were features of the combined cases. Among 49 children with Wilms tumor without aniridia, only 1 had bilateral renal tumors. Using high resolution chromosome banding, Marshall et al. (1982) studied 14 patients with aniridia. Seven were familial and had normal chromosomes; of 7 sporadic cases, 1 showed normal chromosomes and 6 had interstitial deletion of 11p of various lengths. Band 11p13 was included in the deletion in all 6 cases. Little et al. (1993) suggested that the severe nephropathy associated with Denys-Drash syndrome (194080), which frequently leads to early renal failure, may result from the action of altered WT1 in blocking the normal activity of the wildtype protein. In contrast, because of the less severe genital anomalies and apparent lack of nephropathy associated with WAGR, a reduced WT1 dosage during embryogenesis is thought to have a less pronounced effect on development, especially on that of the renal system. Breslow et al. (2000) reviewed nearly 6,000 patients enrolled in 4 clinical trials of the U. S. National Wilms Tumor Study Group between 1969 and 1995 who were followed until death or for a median of 11.0 years of survival for the onset of renal failure. Of 22 patients with Denys-Drash syndrome, 13 developed renal failure; of 46 patients with WAGR, 10 developed renal failure. The cumulative risks of renal failure at 20 years were 62% and 38%, respectively. The findings suggested that nephropathy is not associated uniquely with missense mutations in the WT1 gene and that patients with Wilms tumor and aniridia or genitourinary abnormalities should be followed closely throughout life for signs of nephropathy. - WAGR Syndrome with Atypical Eye Findings Kawase et al. (2001) reported a case of WAGR syndrome with atypical eye findings. The boy presented at 1 month of age with microphthalmos bilaterally, microcornea and corneal cyst in the right eye, and corneal opacity (consistent with Peters anomaly) and absent anterior chamber in the left eye. Electroretinogram was normal in the right eye and subnormal in the left eye, suggesting retinal dysfunction. The child was found to have bilateral Wilms tumors at age 3 years. He also had undescended testes and mental retardation. Chromosome analysis revealed deletion of chromosome 11p15.1-p13.