Frasier syndrome, a potential cause of end-stage renal failure in childhood

Bache, Manon; Dheu, Céline; Doray, Bérénice; Soskin, Sylvie; Paris, Françoise; Sultan, Charles; Fischbach, Michel

doi:10.1007/s00467-009-1343-2

Cited by 14 publications

(12 citation statements)

References 23 publications

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“…Therefore, this paper and other recent reports emphasize the importance of screening patients with SRNS for WT1 mutations (4,29).…”

Section: Discussionmentioning

confidence: 63%

“…Glomerular symptoms in FS patients consist on childhood proteinuria and nephrotic syndrome (NS), characterized by focal and segmental glomerular sclerosis (FSGS). Patients are frequently unresponsive to treatment with steroids and immunosuppressors, and progress to end-stage renal failure in adolescence or early adulthood (3,4 (7). Different mutations in the Wilms' tumor suppressor gene (WT1, OMIM *607102) located in 11p23 may cause either DDS or FS.…”

Section: Discussionmentioning

confidence: 99%

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Frasier syndrome: four new cases with unusual presentations

Guaragna

Lutaif

Bittencourt

et al. 2012

Arq Bras Endocrinol Metab

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SUMMARYFrasier 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. Arq Bras Endocrinol Metab. 2012;56(8):525-32 SUMÁRIO A síndrome de Frasier (SF), caracterizada por disgenesia gonadal e nefropatia, é causada por mutações específicas no gene supressor do tumor de Wilms (WT1) localizado em 11p23. Pacientes com cariótipo 46,XY apresentam genitália feminina normal com gônadas disgenéticas e alto risco de tumor gonadal, principalmente o gonadoblastoma. Por isso, a gonadectomia bilateral eletiva está indicada. A nefropatia na SF consiste de síndrome nefrótica com proteinúria que se inicia na infância e aumenta progressivamente com a idade, principalmente devido à glomeruloesclerose focal e segmentar (GESF). Esses pacientes não respondem ao tratamento com esteroides e imunossupressores e desenvolverão insuficiência renal crônica durante a segunda ou terceira década de vida. Neste trabalho, são relatados quatro casos de SF cujo diagnóstico foi definido após o rastreamento molecular do gene WT1. O caso 1 faz parte de um grande grupo de pacientes que tiveram diagnóstico de síndrome nefrótica corticorresistente e no qual o rastreamento de mutações no fragmento 8-9 do gene WT1 identificou a mutação IVS9+5G>A. Além da SF, essa paciente apresentou características incomuns, tais como malformação urinária (rins em ferradura) e disgerminoma bilateral. Os casos 2 e 3 também apresentaram a mutação IVS9+5G>A, e, no caso 4, foi identificada a mutação IVS9+1G>A, sendo que esse...

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“…Therefore, this paper and other recent reports emphasize the importance of screening patients with SRNS for WT1 mutations (4,29).…”

Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Frasier syndrome: four new cases with unusual presentations

Guaragna

Lutaif

Bittencourt

et al. 2012

Arq Bras Endocrinol Metab

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“…The incidence of 46,XY Frasier syndrome is unknown because it is difficult to distinguish it from Denys-Drash syndrome, another overlapping disease caused by WT1 gene mutations, is difficult and little data is available (20). Since Frasier et al (21) reported the first case in 1964, more than 60 cases have been reported (20, 22, 23). The prevalence of GB in patients with Frasier syndrome is very high.…”

Section: Discussionmentioning

confidence: 99%

Tumors of Bilateral Streak Gonads in Patients with Disorders of Sex Development Containing Y Chromosome Material

Matsumoto

Shimada

Ida

2014

Clin Pediatr Endocrinol

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The presence of Y chromosome material in patients with disorders of sex development (DSD) has been associated with a high risk of gonadoblastoma. Therefore, gonadectomy is recommended in females with bilateral streak gonads and Y chromosome material. The aim of this study was to present our experience with prophylactic gonadectomy in those patients and evaluate their risk of gonadal tumors. We reviewed the charts of 11 female patients who had bilateral gonadectomy (by laparoscopically in 9 patients, by laparotomy in 2 patients) between 1991 and 2012 at our hospital. Seven patients with Turner syndrome (TS) who carry a Y mosaic karyotype in peripheral blood, 3 patients with Swyer syndrome and one patient with Frasier syndrome were included. All patients had an unambiguous female phenotype. Age at surgery and follow-up ranged from 2 to 23 (mean 11) and 0.5 to 20 (mean 8) yr, respectively. Pathologic examination revealed gonadal tumors in 6 of 11 patients (56%), including 4 with TS, the youngest of which was 2 yr old, one with Swyer syndrome and one with Frasier syndrome. A gonadoblastoma was detected in 8 gonads, and an association of dysgerminoma with gonadoblastoma was detected in 2 gonads. Imaging studies showed no metastasis, and the postoperative course was uneventful in all patients. In our series of DSD patients with bilateral streak gonads and Y chromosome material, the risk of gonadal tumor was high. Considering the early occurrence of gonadoblastoma and its high potential for malignant transformation, early prophylactic gonadectomy is strongly recommended.

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“…2 Usual presentation is persistent proteinuria in the first decade and subsequently nephrotic syndrome (NS) that progresses to end-stage renal failure by second or third decade. 3 NS responds poorly to steroid and immunosuppressive agents. 4 …”

Section: Introductionmentioning

confidence: 99%

Frasier syndrome: A rare syndrome with WT-1 gene mutation

Sundaram¹,

Sundari²,

Chinumuthu³

et al. 2017

Int J Contemp Pediatr

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Frasier syndrome is a rare disorder of sex development. It is caused by mutation in Wilms’ tumor suppressor gene (WT-1) located in 11p23. This gene encodes a transcription factor involved in the development of kidney and gonads. The syndrome is characterized by female external genitalia in 46, XY patients, streak gonads with a higher risk of gonadal tumors, mainly gonadoblastoma. Nephropathy consists of nephrotic syndrome (NS) mainly due to focal segmental glomerular sclerosis (FSGS). NS presents early in childhood and responds poorly to steroid and immunosuppressive agents. Progression to End Stage Renal Disease (ESRD) usually occurs by second or third decade of life. We present a 6 years old female child with insignificant past medical history diagnosed as steroid resistant nephrotic syndrome. Renal biopsy showed FSGS. CT Abdomen showed streak gonads with rudimentary uterus. Further genotype showed WT-1 mutation with Karyotype of 46XY. Elective bilateral gonadectomy was done and histopathology showed bilateral dysgerminoma. After a year, her disease progressed to ESRD and she succumbed to the illness.

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Frasier syndrome, a potential cause of end-stage renal failure in childhood

Cited by 14 publications

References 23 publications

Frasier syndrome: four new cases with unusual presentations

Frasier syndrome: four new cases with unusual presentations

Tumors of Bilateral Streak Gonads in Patients with Disorders of Sex Development Containing Y Chromosome Material

Frasier syndrome: A rare syndrome with WT-1 gene mutation

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