FaCD Online Syndrome Fact Sheet

Last updated: 21 Feb 2008

Name: Frasier syndrome

Mode of Inheritance: AD / de novo

Genes

WT1, mapped to 11p13

Tumor features

ovarian gonadoblastoma
Wilms' tumor (nephroblastoma)

Tumor features (possible)

ovarian dysgerminoma
ovarian germ cell tumor

Non-tumor features

ambiguous external genitals in 46,XY
male (46,XY) pseudohermaphroditism
nephropathy
streak ovaries

Comment

Clinical hallmarks are male (46,XY) pseudohermaphroditism with streak gonads, nephropathy, gonadoblastoma (associated with 46,XY cases) and occasionally dysgerminoma[1,4]. In 46,XX cases there is no or little disturbance of gonadal differentiation and no gonadal tumors have been reported. There is an obvious similarity with Denys-Drash syndrome, however, Wilms tumors are rare in patients with Frasier syndrome [2] and their nephropathy is of later onset than that observed in Denys-Drash syndrome (DDS). Frasier syndrome is caused by a specific heterozygous splicing mutation in WT1[2;3]. DDS patients demonstrate diffuse mesangial sclerosis, whereas focal and segmental glomerulosclerosis is seen in Frasier syndrome patients. Both conditions should be regarded as part of the spectrum associated with germline WT1 mutations.

References

[1] Moorthy AV, Chesney RW, Lubinsky M. Chronic renal failure and XY gonadal dysgenesis: "Frasier" syndrome--a commentary on reported cases. Am J Med Genet Suppl 1987; 3: 297-302:297-302.
[2] Barbosa AS, Hadjiathanasiou CG, Theodoridis C, Papathanasiou A, Tar A, Merksz M, Gyorvari B, Sultan C, Dumas R, Jaubert F, Niaudet P, Moreira CA, Cotinot C, Fellous M. The same mutation affecting the splicing of WT1 gene is present on Frasier syndrome patients with or without Wilms' tumor. Hum Mutat 13[2], 146-153. 1999.
[3] Klamt B, Koziell A, Poulat F, Wieacker P, Scambler P, Berta P, Gessler M. Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms. Hum Mol Genet 7[4], 709-714. 1998.
[4] Love JD, DeMartini SD, Coppola CP. Prophylactic bilateral salpingo-oopherectomy in a 17-year-old with Frasier syndrome reveals gonadoblastoma and seminoma: a case report. Journal of pediatric surgery 2006; 41(11):e1-4.