Wilms tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome is a contiguous gene deletion syndrome involving the Wilms tumor 1 gene (WT1), the paired box gene 6 (PAX6), and possibly other genes on chromosome 11p13. WT1 is required for normal formation of the genitourinary system and the high incidence of Wilms tumor and genitourinary anomalies found in patients with WAGR are attributed to haploin-sufficiency of this gene. It has been hypothesized that WT1 also plays an important role in the development of the diaphragm. During mammalian embryonic development, WT1 is expressed in the pleural and abdominal mesothelium that forms part of the diaphragm. Furthermore, mice that are homozygous for a deletion in the mouse homolog of WT1 have diaphragmatic hernias. Case reports describing congenital diaphragmatic hernias in infants with Denys-Drash and Frasier syndromes, both of which can be caused by mutations in WT1, provide additional support for this hypothesis. We report an infant with aniridia, bilateral cryptorchidism, vesicoureteral reflux, and a right-sided Morgagni-type diaphragmatic hernia. G-banded chromosome analysis revealed a deletion of 11p12-p15.1. Breakpoint regions were refined by fluorescence in situ hybridization (FISH) and deletion of the WAGR critical region, including WT1, was confirmed. A review of the medical literature identified a second patient with a deletion of 11p13, a left-sided Bochdalek-type diaphragmatic hernia, and anomalies that suggest a diagnosis of WAGR including bilateral microphthalmia, a small penis, bilateral cryptorchidism, and a hypoplastic scrotum. These cases demonstrate that congenital diaphragmatic hernia can be associated with WAGR syndrome and suggest that deletions of WT1 may predispose individuals to develop congenital diaphragmatic hernia. (c) 2005 Wiley-Liss, Inc.
