Gonadal Tumor in Frasier Syndrome: A Review and Classification

摘要

Abstract 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 8 8 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. Introduction Frasier syndrome and Denys-Drash syndrome (DDS) are both rare inherited diseases characterized by steroid-resistant nephrotic syndrome, which leads to renal failure, gonadal tumor (most commonly gonadoblastoma or dysgerminoma), and male pseudohermaphroditism (female external genitalia with sex chromosomes XY; ref. 1). In comparison with other conditions in which male pseudohermaphroditism is present, the risk of gonadal tumor is particularly high in Frasier syndrome (60% compared with 40% for DDS and 15% for partial androgen insensitivity syndrome; ref. 2). Early diagnosis and early elective bilateral gonadectomy have, therefore, been recommended for patients with Frasier syndrome and DDS (3, 4).