title: Frasier syndrome: four new cases with unusual presentations.
abstract: Frasier syndrome (FS) is characterized by gonadal dysgenesis and nephropathy. It is caused by specific mutations in the Wilms' tumor suppressor gene (WT1) located in 11p23. Patients with the 46,XY karyotype present normal female genitalia with streak gonads, and have higher risk of gonadal tumor, mainly, gonadoblastoma. Therefore, elective bilateral gonadectomy is indicated. Nephropathy in FS consists in nephrotic syndrome (NS) with proteinuria that begins early in childhood and progressively increases with age, mainly due to nonspecific focal and segmental glomerular sclerosis (FSGS). Patients are generally unresponsive to steroid and immunosuppressive therapies, and will develop end-stage renal failure (ESRF) during the second or third decade of life. We report here four cases of FS diagnosis after identification of WT1 mutations. Case 1 was part of a large cohort of patients diagnosed with steroid-resistant nephrotic syndrome, in whom the screening for mutations within WT1 8-9 hotspot fragment identified the IVS9+5G>A mutation. Beside FS, this patient showed unusual characteristics, such as urinary malformation (horseshoe kidney), and bilateral dysgerminoma. Cases 2 and 3, also bearing the IVS9+5G>A mutation, and case 4, with IVS9+1G>A mutation, were studied due to FSGS and/or delayed puberty; additionally, patients 2 and 4 developed bilateral gonadal tumors. Since the great majority of FS patients have normal female external genitalia, sex reversal is not suspected before they present delayed puberty and/or primary amenorrhea. Therefore, molecular screening of WT1 gene is very important to confirm the FS diagnosis.
authors.affiliation: Centro de Biologia Molecular e Engenharia Genética, Universidade Estadual de Campinas, Campinas, SP, Brazil.
authors.forename: Mara Sanches
authors.initials: MS
authors.lastname: Guaragna
authors.forename: Anna Cristina Gervásio de Britto
authors.initials: AC
authors.lastname: Lutaif
authors.forename: Viviane Barros
authors.initials: VB
authors.lastname: Bittencourt
authors.forename: Cristiane Santos Cruz
authors.initials: CS
authors.lastname: Piveta
authors.forename: Fernanda Caroline
authors.initials: FC
authors.lastname: Soardi
authors.forename: Luiz Claudio Gonçalves
authors.initials: LC
authors.lastname: Castro
authors.forename: Vera Maria Santoro
authors.initials: VM
authors.lastname: Belangero
authors.forename: Andréa Trevas
authors.initials: AT
authors.lastname: Maciel-Guerra
authors.forename: Gil
authors.initials: G
authors.lastname: Guerra-Junior
authors.forename: Maricilda Palandi De
authors.initials: MP
authors.lastname: Mello
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D052159:Frasier Syndrome / Q000175:diagnosis / Q000235:genetics*; D018238:Gonadoblastoma / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D025721:WT1 Proteins