King Thomas F J, Conway Gerard S
Institute for Women's Health, University College London Hospitals, London, UK.
Curr Opin Endocrinol Diabetes Obes. 2014 Dec;21(6):504-10. doi: 10.1097/MED.0000000000000113.
This review focuses on the pathogenesis, diagnosis, management and long-term outcomes of disorders of sex development, specifically women with Swyer syndrome (46,XY complete gonadal dysgenesis).
Recent discoveries have broadened our understanding of the complex pathways involved in normal and abnormal sex development. In 46,XY gonadal dysgenesis, lack of testis development may be triggered by sex determining region Y, NR5A1, DHH or testis-determining gene loss-of-function mutations, DAX1 or WNT4 duplication or MAP3K1 gain-of-function mutations. The diagnosis and management of patients with Swyer syndrome is complex, and optimal care requires an experienced multidisciplinary team. Early diagnosis is vital because of the significant risk of germ cell tumour, and bilateral gonadectomy should be performed. Furthermore, early sex hormone treatment is necessary to induce and maintain typical pubertal development and to achieve optimal bone mineral accumulation. Pregnancy is possible via ova donation, and outcomes are similar to women with 46,XX ovarian failure.
Further pathogenic gene mutations are likely to be identified, and the function, interaction and phenotypic effects of new and existing mutations will be further defined. Patients require long-term follow-up in specialist centres.
本综述聚焦于性发育障碍的发病机制、诊断、管理及长期预后，尤其关注患有斯维尔综合征（46,XY完全性性腺发育不全）的女性。
近期的研究发现拓宽了我们对正常及异常性发育所涉及的复杂通路的理解。在46,XY性腺发育不全中，睾丸发育缺失可能由Y染色体性别决定区、NR5A1、DHH或睾丸决定基因功能丧失性突变、DAX1或WNT4重复或MAP3K1功能获得性突变引发。斯维尔综合征患者的诊断和管理较为复杂，最佳治疗需要一个经验丰富的多学科团队。由于存在患生殖细胞肿瘤的重大风险，早期诊断至关重要，且应进行双侧性腺切除术。此外，早期性激素治疗对于诱导和维持典型的青春期发育以及实现最佳骨矿物质积累是必要的。通过卵子捐赠有可能怀孕，其结果与46,XX卵巢功能衰竭的女性相似。
可能会鉴定出更多致病基因突变，新的和现有的突变的功能、相互作用及表型效应将得到进一步明确。患者需要在专科中心进行长期随访。
