Chronic renal failure and XY gonadal dysgenesis: “Frasier” syndrome—a commentary on reported cases

Abstract

The development of chronic renal failure because of parenchymatous renal disease in patients in 46,XY gonadal dysgenesis was noted initially by Drash et al [J Pediatr 76:585–593,1970]. However, we think that some of the cases reported as examples of the Drash syndrome are a different disorder. In this paper, we review six previously reported patients with streak gonads, pseudohermaphroditism, and renal failure. In several of these patients the diagnosis was established only after a successful kidney transplantation during evaluation for primary amenorrhea. Gonadoblastoma arising from the streak gonad was noted in five of the six patients. “Frasier” syndrome would be a suitable term to denote this association after Frasier et al, who described two patients in 1964. We recommend evaluation of the gonads in prepubertal girls with end‐stage renal disease at risk for this syndrome.

Podocyte Differentiation and Hereditary Proteinuria/Nephrotic Syndromes

“…In Denys-Drash syndrome, characterized by the association of early-onset glomerulopathy with diffuse mesangial sclerosis, gonadal dysgenesis leading to pseudohermaphroditism in males, and a high risk of developing Wilms' tumor (40 -42), dominant negative point mutations affect the zinc fingers of the WT1 protein and, consequently, its binding to DNA (43) and result in abnormal podocyte expression of PAX2 and growth factors PDGF and TGF-␤1 (44). Mutations are different in Frasier syndrome, characterized by male pseudohermaphroditism with complete sex reversal and streak gonads frequently at the origin of gonadoblastomas, associated with slowly progressive glomerulopathy (45). They are intronic mutations in the second splicing site of the gene (46).…”

Lack of Puberty Despite Elevated Estradiol in a 46,XY Phenotypic Female with Frasier Syndrome

“…In 1964, Frasier et al reported phenotypic female identical twins with XY gonadal dysgenesis with streak gonads, gonadoblastoma, and chronic kidney failure [7]. Similar patients were subsequently described, and in 1987 Moorthy et al collected 6 patients and proposed that these symptoms should be called Frasier syndrome (FS) [8]. FS is caused by mutation in the WT1 gene, which is located on chromosome 11p13.…”

Mechanisms of Glucocorticoid Resistance in Idiopathic Nephrotic Syndrome

“…It has been shown that, in the podocytes of DDS patients, WT1 mutants result in overexpression of Pax-2, which should be repressed after early nephrogenesis [110]. Second, mutations in the donor splice site at intron 9 lead to Frasier syndrome (FS), which is described as a combination of complete XY gonadal dysgenesis, FSGS and gonadoblastoma in 46, XY patients and as nephropathy alone in 46, XX patients [121]. The third nephropathy is isolated SRNS.…”