Frasier syndrome: ambiguous genitalia and end-stage chronic kidney disease in childhood. Case report
Keywords:
Frasier syndrome, ambiguous genitalia, end-stage kidney disease, Wilms tumor
Abstract
We report the case of a patient with Frasier syndrome: nephropathy, gonadal dysgenesis and progressive and severe kidney damage during childhood. Frasier syndrome is a rare disorder that causes end-stage chronic kidney disease, usually in young adults —second or third decades of life. Nephropathy presents with proteinuria, beginning during childhood, occasionally with nephrotic syndrome; its characteristic histological lesion is a focal segmental glomerulosclerosis, resistant to treatment with corticosteroids and/or immunosuppressants. Frasier syndrome is caused by mutations in the Wilms’ tumor suppressor gene, or WT1 gene, located on the short arm of chromosome 11: Cr11p23.
References
1) Barbaux S, Niaudet P, Gubler MC, Grünfeld JP, Jaubert F, Kuttenn F, et al. Donor splice-site mutations in WT1 are responsible for Frasier syndrome. Nat Genet. 1997;17(4):467-70. doi: 10.1038/ng1297-467.
2) Frasier SD, Bashore RA, Mosier HD. Gonadoblastoma associated with pure gonadal dysgenesis in monozygous twins. J Pediatr. 1964;64:740-5. doi: 10.1016/s0022-3476(64)80622-3.
3) Berta P, Morin D, Poulat F, Taviaux S, Lobaccaro JM, Sultan C, et al. Molecular analysis of the sex-determining region from the Y chromosome in two patients with Frasier syndrome. Horm Res. 1992;37(3):103-6. doi: 10.1159/000182291.
4) Blanchet P, Daloze P, Lesage R, Papas S, Van Campenhout J. XY gonadal dysgenesis with gonadoblastoma discovered after kidney transplantation. Am J Obstet Gynecol. 1977;129(2):221-2. doi: 10.1016/0002-9378(77)90751-7.
5) Klamt B, Koziell A, Poulat F, Wieacker P, Scambler P, Berta P, et al. Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms. Hum Mol Genet. 1998;7(4):709-14. doi: 10.1093/hmg/7.4.709.
6) Hernández Fernández RA. El tumor de Wilms. Un paradigma de heterogeneidad genética. Rev Haban Cienc Méd. 2011;10(2):213-23.
7) Moorthy AV, Chesney RW, Lubinsky M. Chronic renal failure and XY gonadal dysgenesis: “Frasier” síndrome. A commentary on reported cases. Am J Med Genet Suppl. 1987;3:297-302. doi: 10.1002/ajmg.1320280535.
8) Melo KF, Martin RM, Costa EM, Carvalho FM, Jorge AA, Arnhold IJ, et al. 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. 2002;87(6):2500-5. doi: 10.1210/jcem.87.6.8521.
9) Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, et al. Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell. 1991;67(2):437-47. doi: 10.1016/0092-8674(91)90194-4.
10) Poulat F, Morin D, König A, Brun P, Giltay J, Sultan C, et al. Distinct molecular origins for Denys-Drash and Frasier syndromes. Hum Genet. 1993;91(3):285-6. doi: 10.1007/BF00218274.
11) Comité de Nefrología, Sociedad Argentina de Pediatría. Consenso de tratamiento del síndrome nefrótico en la infancia. Arch Argent Pediatr. 2014;112(3):277-84. doi: 10.5546/aap.2014.277.
12) Kidney Disease: improvement global outcome (KDIGO), the 15th Congress of the International Pediatric Nephrology Association (IPNA), held on August 29–September 2, 2010, NY, USA.
13) De la Hoz Mendoza IR, Santana Fontalvo MM. Síndrome nefrótico resistente a corticoides en pediatría, actualización. Biociencias. 2016;11(2):17-28.
14) Bache M, Dheu C, Doray B, Fothergill H, Soskin S, Paris F, et al. Frasier syndrome, a potential cause of end-stage renal failure in childhood. Pediatr Nephrol. 2010;25(3):549-52. doi: 10.1007/s00467-009-1343-2.
15) Buzi F, Mella P, Pilotta A, Felappi B, Camerino G, Notarangelo LD. Frasier syndrome with childhood-onset renal failure. Horm Res. 2001;55(2):77-80. doi: 10.1159/000049974.
2) Frasier SD, Bashore RA, Mosier HD. Gonadoblastoma associated with pure gonadal dysgenesis in monozygous twins. J Pediatr. 1964;64:740-5. doi: 10.1016/s0022-3476(64)80622-3.
3) Berta P, Morin D, Poulat F, Taviaux S, Lobaccaro JM, Sultan C, et al. Molecular analysis of the sex-determining region from the Y chromosome in two patients with Frasier syndrome. Horm Res. 1992;37(3):103-6. doi: 10.1159/000182291.
4) Blanchet P, Daloze P, Lesage R, Papas S, Van Campenhout J. XY gonadal dysgenesis with gonadoblastoma discovered after kidney transplantation. Am J Obstet Gynecol. 1977;129(2):221-2. doi: 10.1016/0002-9378(77)90751-7.
5) Klamt B, Koziell A, Poulat F, Wieacker P, Scambler P, Berta P, et al. Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms. Hum Mol Genet. 1998;7(4):709-14. doi: 10.1093/hmg/7.4.709.
6) Hernández Fernández RA. El tumor de Wilms. Un paradigma de heterogeneidad genética. Rev Haban Cienc Méd. 2011;10(2):213-23.
7) Moorthy AV, Chesney RW, Lubinsky M. Chronic renal failure and XY gonadal dysgenesis: “Frasier” síndrome. A commentary on reported cases. Am J Med Genet Suppl. 1987;3:297-302. doi: 10.1002/ajmg.1320280535.
8) Melo KF, Martin RM, Costa EM, Carvalho FM, Jorge AA, Arnhold IJ, et al. 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. 2002;87(6):2500-5. doi: 10.1210/jcem.87.6.8521.
9) Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, et al. Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell. 1991;67(2):437-47. doi: 10.1016/0092-8674(91)90194-4.
10) Poulat F, Morin D, König A, Brun P, Giltay J, Sultan C, et al. Distinct molecular origins for Denys-Drash and Frasier syndromes. Hum Genet. 1993;91(3):285-6. doi: 10.1007/BF00218274.
11) Comité de Nefrología, Sociedad Argentina de Pediatría. Consenso de tratamiento del síndrome nefrótico en la infancia. Arch Argent Pediatr. 2014;112(3):277-84. doi: 10.5546/aap.2014.277.
12) Kidney Disease: improvement global outcome (KDIGO), the 15th Congress of the International Pediatric Nephrology Association (IPNA), held on August 29–September 2, 2010, NY, USA.
13) De la Hoz Mendoza IR, Santana Fontalvo MM. Síndrome nefrótico resistente a corticoides en pediatría, actualización. Biociencias. 2016;11(2):17-28.
14) Bache M, Dheu C, Doray B, Fothergill H, Soskin S, Paris F, et al. Frasier syndrome, a potential cause of end-stage renal failure in childhood. Pediatr Nephrol. 2010;25(3):549-52. doi: 10.1007/s00467-009-1343-2.
15) Buzi F, Mella P, Pilotta A, Felappi B, Camerino G, Notarangelo LD. Frasier syndrome with childhood-onset renal failure. Horm Res. 2001;55(2):77-80. doi: 10.1159/000049974.
Published
2021-06-22
How to Cite
1.
Aralde A, Montanari D, Fernández SA, Barros MI, Gargiulo C. Frasier syndrome: ambiguous genitalia and end-stage chronic kidney disease in childhood. Case report. Rev Nefrol Dial Traspl. [Internet]. 2021Jun.22 [cited 2024Jul.16];41(2):130-4. Available from: http://revistarenal.org.ar/index.php/rndt/article/view/650
Section
Case Report
Copyright (c) 2021 Revista de Nefrología, Diálisis y Trasplante
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
