DOI: http://dx.doi.org/10.18203/2349-3291.ijcp20171736

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

Vindhiya Kadambavana Sundaram, Sundari Subramanian, Lakshmi Charan Chinumuthu, Aishwarya Dharmanathan

Abstract


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.


Keywords


Frasier syndrome, Gonadoblastoma, Nephrotic syndrome

Full Text:

PDF

References


Hersmus R, van der Zwan YG, Stoop H, Bernard P, Sreenivasan R, Oosterhuis JW, et al. A 46, XY female DSD patient with bilateral gonadoblastoma, a novel SRY missense mutation combined with a WT1 KTS splice-site mutation. PLoS One. 2012;7:40858.

Koziell A, Grundy R. Frasier and Denys-Drash syndromes: different disorders or part of a spectrum: Arch Dis Child. 1999;81:365-9.

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;25:549-52.

Chernin G, Vega-Warner V, Schoeb DS, Heeringa SF, Ovunc B, Saisawat P, et al. Genotype/phenotype correlation in nephrotic syndrome caused by WT1 mutations. Clin J Am Soc Nephrol. 2010;5:1655-62.

Esin S, Baser E, Kucukozkan T, Magden HA. Ovarian gonadoblastoma with dysgerminomaina 15-year-old girl with 46, XX karyotype: case report and review of the literature. Arch Gynecol Obstet. 2012;285:447-51.

Kanagal DV, Prasad K, Rajesh A, Kumar RG, Cherian S, Shetty H, et al. Ovarian Gonadoblastoma with Dysgerminoma in a Young Girl with 46, XX Karyotype: a Case Report. J Clin Diagn Res. 2013;7:2021-2.

Hughes IA, Houk C, Ahmed SF, Lee PA. Consensus statement on management of intersex disorders. J Pediatr Urol. 2006;2:148-62.

Santín S, Bullich G, Tazón-Vega B, García-Maset R, Giménez I, Silva I, et al. Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2011;6(5):1139-48.

Ezaki J, Hashimoto K, Asano T, Kanda S, Akioka Y, Hattori M et al. Gonadal Tumor in Frasier Syndrome: A Review and Classification. Cancer Prev Res (Phila). 2015;8(4):271-6.

Guaragna MS, Lutaif AC, Bittencourt VB, Piveta CS, Soardi FC, Castro LC et al. Frasier syndrome: four new cases with unusual presentations. Arq Bras Endocrinol Metabol. 2012;56(8):525-32.