Sertoli cell tumor and gonadoblastoma in an untreated 29-year-old 46,XY phenotypic male with Frasier syndrome carrying a WT1 IVS9+4C>T mutation.
OBJECTIVE
Frasier syndrome (FS) phenotype in 46,XY patients usually consists of female external genitalia, gonadal dysgenesis, high risk of gonadoblastoma and the development of end stage renal failure usually in the second decade of life. FS is caused by heterozygous de novo intronic splice site mutations of the Wilms' tumor suppressor gene 1 (WT1), although a few cases with typical exonic WT1 Denys-Drash mutations that resemble an FS phenotype have been described. The aim of this study was to present further data on the spectrum of FS phenotypes through the evaluation of a 29-year-old patient with a predominantly male phenotype and coexistence of Sertoli cell tumor and gonadoblastoma.


RESULTS
Genetic analysis using standard methods for DNA sequencing confirmed FS due to a WT1 gene mutation, IVS9+4C>T.


CONCLUSIONS
This very rare case illustrates the natural course of FS over many years due to the neglect by the patient to address his need for follow-up, while adding further data on the spectrum of FS phenotypes associated with IVS9+4 C>T mutations. The coexistence of the rare Sertoli cell tumor and gonadoblastoma emphasizes that early clinical recognition and molecular identification facilitates appropriate patient management, especially with respect to the high risk of gonadal malignancy.
Department of Medical Genetics, Medical School, University of Athens, Aghia Sophia Children's Hospital, Athens, Greece.
Sophia
S
Kitsiou-Tzeli
Maria
M
Deligiorgi
Sophia
S
Malaktari-Skarantavou
Charalampos
C
Vlachopoulos
Spyridon
S
Megremis
Irene
I
Fylaktou
Joanne
J
Traeger-Synodinos
Christina
C
Kanaka-Gantenbein
Christodoulos
C
Stefanadis
Emmanuel
E
Kanavakis
D000328:Adult; D002648:Child; D002675:Child, Preschool; D052159:Frasier Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D018238:Gonadoblastoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D012707:Sertoli Cell Tumor / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D025721:WT1 Proteins / Q000235:genetics*
D025721:WT1 Proteins