Gonadal tumor in Frasier syndrome: A review and classification

Frasier syndrome is a rare inherited disease characterized by steroid-resistant nephrotic syndrome, gonadal tumor, and male pseudohermaphroditism (female external genitalia with sex chromosomes XY), which is based on a splice site mutation of Wilms tumor-suppressor gene 1 ( WT1 ). Several unusual Frasier syndrome cases have been reported in which male pseudohermaphroditism was absent. We reviewed 88 Frasier syndrome cases in the literature and classified them into three types (type 1–3) according to external genitalia and sex chromosomes, and described their clinical phenotypes. Type 1 Frasier syndrome is characterized by female external genitalia with 46,XY ( n = 72); type 2 by male external genitalia with 46,XY ( n = 8); and type 3 by female external genitalia with 46,XX ( n = 8). Clinical course differs markedly among the types. Although type 1 is noticed at the mean age of 16 due to mainly primary amenorrhea, type 2 and 3 do not present delayed secondary sex characteristics, making diagnosis difficult. The prevalence of gonadal tumor is high in type 1 (67%) and also found in 3 of the 8 type 2 cases, but not in any type 3 cases, which emphasize that preventive gonadectomy is unnecessary in type 3. On the basis of our findings, we propose a new diagnostic algorithm for Frasier syndrome. Cancer Prev Res; 8(4); 271–6. ©2015 AACR .