Ezaki Jiro, Hashimoto Kazunori, Asano Tatsuo, Kanda Shoichiro, Akioka Yuko, Hattori Motoshi, Yamamoto Tomoko, Shibata Noriyuki
The Medical Training Center for Graduates, Tokyo Women's Medical University, Tokyo, Japan. Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo, Japan.
Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, Japan.
Cancer Prev Res (Phila). 2015 Apr;8(4):271-6. doi: 10.1158/1940-6207.CAPR-14-0415. Epub 2015 Jan 26.
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.
弗雷泽综合征是一种罕见的遗传性疾病，其特征为类固醇抵抗性肾病综合征、性腺肿瘤和男性假两性畸形（具有XY性染色体的女性外生殖器），该病基于威尔姆斯肿瘤抑制基因1（WT1）的剪接位点突变。已有数例不伴有男性假两性畸形的特殊弗雷泽综合征病例报道。我们回顾了文献中的88例弗雷泽综合征病例，并根据外生殖器和性染色体将其分为三种类型（1 - 3型），并描述了它们的临床表型。1型弗雷泽综合征的特征是具有46,XY核型的女性外生殖器（n = 72）；2型为具有46,XY核型的男性外生殖器（n = 8）；3型为具有46,XX核型的女性外生殖器（n = 8）。各型的临床病程差异显著。虽然1型主要因原发性闭经在平均16岁时被发现，但2型和3型不存在继发性性征延迟，这使得诊断困难。1型性腺肿瘤的患病率很高（67%），在8例2型病例中有3例也发现了性腺肿瘤，但3型病例中均未发现，这强调3型无需进行预防性性腺切除术。基于我们的研究结果，我们提出了一种新的弗雷泽综合征诊断算法。
