Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Pediatric Nephrology
Published in: Pediatric Nephrology 10/2010

01-10-2010 | Brief Report

Frasier syndrome: early gonadoblastoma and cyclosporine responsiveness

Authors: Aditi Sinha, Sonika Sharma, Ashima Gulati, Alok Sharma, Sandeep Agarwala, Pankaj Hari, Arvind Bagga

Published in: Pediatric Nephrology | Issue 10/2010

Login to get access

Abstract

Frasier syndrome is characterized by progressive glomerulopathy that is unresponsive to corticosteroids, male pseudohermaphroditism, and an increased risk of genitourinary tumors. Of 21 girls with steroid-resistant nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS) who were screened for mutations in the WT1 gene, two showed Frasier syndrome. Both patients had donor splice-site mutations in intron 9 of the WT1 gene and a male karyotype (46, XY). Long-term therapy with cyclosporine resulted in partial remission in both cases. One patient showed foci of gonadoblastoma in the excised dysgenetic gonads. This report highlights the need for screening for mutations in the WT1 gene in girls with steroid-resistant FSGS. Patients with Frasier syndrome might benefit from early gonadectomy.
Literature
1.
Barbaux S, Niaudet P, Gubler MC, Grunfeld JP, Jaubert F, Kuttenn F, Fekete CN, Souleyreau-Therville N, Thibaud E, Fellous M, McElreavey K (1997) Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet 17:467–470CrossRefPubMed
2.
Wagner N, Wagner KD, Xing Y, Scholz H, Schedl A (2004) The major podocyte protein nephrin is transcriptionally activated by the Wilms’ tumor suppressor WT1. J Am Soc Nephrol 15:3044–3051CrossRefPubMed
3.
Klamt B, Koziell A, Poulat F, Wieacker P, Scambler P, Berta P, Gessler M (1998) Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/–KTS splice isoforms. Hum Mol Genet 7:709–714CrossRefPubMed
4.
Mucha B, Ozaltin F, Hinkes BD, Hasselbacher K, Ruf RG, Schutheiss M, Hangan D, Hoskins BE, Everding AS, Bogdanovic R, Seeman T, Hoppe B, Hildebrandt F, Members of the APN Study Group (2006) Mutations in the Wilms’ tumor 1 gene cause isolated steroid resistant nephrotic syndrome and occur in exons 8 and 9. Pediatr Res 59:325–331CrossRefPubMed
5.
Aucella F, Bisceglia L, De Bonis P, Gigante M, Caridi G, Barbano G, Mattioli G, Perfumo F, Gesualdo L, Ghiggeri GM (2006) WT1 mutations in nephrotic syndrome revised. High prevalence in young girls, associations and renal phenotypes. Pediatr Nephrol 21:1393–1398CrossRefPubMed
6.
Cho HY, Lee JH, Choi HJ, Lee BH, Ha IS, Choi Y, Cheong HI (2008) WT1 and NPHS2 mutations in Korean children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 23:63–70CrossRefPubMed
7.
Ruf RG, Schultheiss M, Lichtenberger A, Karle SM, Zalewski I, Mucha B, Everding AS, Neuhaus T, Patzer L, Plank C, Haas JP, Ozaltin F, Imm A, Fuchshuber A, Bakkaloglu A, Hildebrandt F (2004) Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome. Kidney Int 66:564–570CrossRefPubMed
8.
Malina M, Cinek O, Janda J, Seeman T (2009) Partial remission with cyclosporine A in a patient with nephrotic syndrome due to NPHS2 mutation. Pediatr Nephrol 24:2051–2053CrossRefPubMed
9.
Gellermann J, Querfeld U (2008) Case report: long-term immunosuppressive treatment of FSGS due to WT1 mutations. Pediatr Nephrol 23:1639, abstract P171
10.
Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, Reiser J, Mundel P (2008) The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 14:931–938CrossRefPubMed
11.
12.
Joki-Erkkila MM, Karikoski R, Rantala I, Lenko HL, Visakorpi T, Heinonen PK (2002) Gonadoblastoma and dysgerminoma associated with XY gonadal dysgenesis in a adolescent with chronic renal failure: a case of Frasier syndrome. J Pediatr Adolesc Gynecol 15:145–149CrossRefPubMed
13.
Frasier SD, Bashore RA, Mosier HD (1964) Gonadoblastoma associated with pure gonadal dysgenesis in monozygotic twins. J Pediatr 64:740–745CrossRefPubMed
14.
Tajima T, Sasaki S, Tanaka Y, Kusunoki H, Nagashima T, Nonomura K, Fujieda K (2003) 46, XY phenotypic male with focal segmental glomerulosclerosis caused by the WT1 splice site mutation. Horm Res 60:302–305CrossRefPubMed
15.
Saxena AK, van Tuil C, Schultze-Everding A (2006) Frasier syndrome in a pre-menarchal girl: laparoscopic resection of gonadoblastoma. Eur J Pediatr 165:917–919CrossRefPubMed
16.
Blanchet P, Daloze P, Lesage R, Papas S, Compenhout JV (1977) XY gonadal dysgenesis with gonadoblastoma discovered after kidney transplantation. Am J Obstet Gynecol 129:221–222PubMed
17.
Simpson JL D, Chaganti RSK, Mourandian J, German J (1982) Chronic renal disease, myotonic dystrophy and gonadoblastoma in XY gonadal dysgenesis. J Med Genet 79:73–76CrossRef
18.
Haning RV Jr, Chesney RW, Moorthy AV, Gilbert EF (1985) A syndrome of chronic renal failure and XY gonadal dysgenesis in young phenotypic females without gonadal ambiguity. Am J Kidney Dis 6:40–48PubMed
19.
Kikuchi H, Takata A, Akasaka Y, Fukuzawa R, Yoneyama H, Kurosawa Y, Honda M, Kamiyama Y, Hata J (1998) Do intronic mutations affecting splicing of WT1 exon 9 cause Frasier syndrome? J Med Genet 35:45–48CrossRefPubMed
20.
Kohsaka T, Tagawa M, Takekoshi Y, Yanagisawa H, Tadokoro K, Yamada M (1999) Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome. Hum Mutat 14:466–470CrossRefPubMed
21.
Okuhara K, Tajima T, Nakae J, Sasaki S, Tochimaru H, Abe S, Fujieda K (1999) A Japanese case with Frasier syndrome caused by the splice junction mutation of WT1 gene. Endocr J 46:639–642CrossRefPubMed
22.
Koziell A, Charmandari E, Hindmarsh PC Rees L, Scambler P, Brook CG (2000) Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy. Clin Endocrinol 52:519–524CrossRef
23.
Melo KFS, Martin RM, Costa EMF, Carvalho FM, Jorge AA, Arnhold IJP, Mendonca BB (2002) An unusual phenotype of Frasier syndrome due to IVS9 +4C>T mutation in the WT1 gene: predominantly male ambiguous genitalia and absence of gonadal dysgenesis. J Clin Endocrinol Metab 87:2500–2505CrossRefPubMed
24.
Perez de Nanclares G, Castano L, Bilbao JR, Vallo A, Rica I, Vela A, Martul P (2002) Molecular analysis of Frasier syndrome: mutation in the WT1 gene in a girl with gonadal dysgenesis and nephronophthisis. J Pediatr Endocrinol Metab 15:1047–1050PubMed
25.
Shimoyama H, Nakajima M, Naka H, Park YD, Hori K, Morikawa H, Yoshioka A (2002) A girl with bilateral ovarian tumors: Frasier syndrome. Eur J Pediatr 161:81–83CrossRefPubMed
26.
Love JD, DeMartini SD, Coppola CP (2006) Prophylactic bilateral salpingo-oopherectomy in a 17-year-old with Frasier syndrome reveals gonadoblastoma and seminoma: a case report. J Pediatr Surg 41:E1–E4CrossRefPubMed
27.
De Andrade JGR, Guaragna MS, Soardi FC, Guerra-Junior G, De Mello MP, Maciel-Guerra AT (2008) Clinical and genetic findings of five patients with WT1-related disorders. Arq Bras Endocrinol Metab 52:1236–1243CrossRef
28.
Subbiah V, Huff V, Wolff JE, Ketonen L, Lang FF Jr, Stewart J, Langford L, Herzog CE (2009) Bilateral gonadoblastoma with dysgerminoma and pilocytic astrocytoma with WT1 GT-IVS9 mutation: a 46 XY phenotypic female with Frasier syndrome. Pediatr Blood Cancer 53:1349–1351CrossRefPubMed
Metadata
Title
Frasier syndrome: early gonadoblastoma and cyclosporine responsiveness
Authors
Aditi Sinha
Sonika Sharma
Ashima Gulati
Alok Sharma
Sandeep Agarwala
Pankaj Hari
Arvind Bagga
Publication date
01-10-2010
Publisher
Springer-Verlag
Published in
Pediatric Nephrology / Issue 10/2010
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-010-1518-x

Other articles of this Issue 10/2010

Pediatric Nephrology 10/2010 Go to the issue

Letter to the Editors

Homozygous NPHP1 deletions in Egyptian children with nephronophthisis including an infantile onset patient

Brief Report

Long-term remission of nephrotic syndrome with etanercept for concomitant juvenile idiopathic arthritis

Original Article

Peritonitis in children on peritoneal dialysis in Cape Town, South Africa: epidemiology and risks

Original Article

Evaluating different imaging strategies in children after first febrile urinary tract infection

Original Article

The IL-6 −174G/C polymorphism and renal scarring in children with first acute pyelonephritis

Educational Review

Glomerulocystic kidney disease