Molecular Genetics and Development Division, Prince Henry's Institute of Medical Research, Monash Medical Centre, Department of Anatomy and Biochemistry, Monash University, Clayton, Melbourne, VIC, Australia.
Nat Rev Endocrinol. 2013 Feb;9(2):79-91. doi: 10.1038/nrendo.2012.235. Epub 2012 Dec 18.
Formerly known as 'intersex' conditions, disorders of sex development (DSDs) are congenital conditions in which chromosomal, gonadal or anatomical sex is atypical. A complete revision of the nomenclature and classification of DSDs has been undertaken, which emphasizes the genetic aetiology of these disorders and discards pejorative terms. Uptake of the new terminology is widespread. DSDs affecting gonadal development are perhaps the least well understood. Unravelling the molecular mechanisms underlying gonadal development has revealed new causes of DSDs, although a specific molecular diagnosis is made in only ∼20% of patients. Conversely, identification of the molecular causes of DSDs has provided insight into the mechanisms of gonadal development. Studies of N-ethyl-N-nitrosourea mutagenesis in the mouse, and multigene diagnostic screening and genome-wide approaches, such as array-comparative genomic hybridization and next-generation sequencing, in patients with DSDs are accelerating the discovery of genes involved in gonadal development and DSDs. Furthermore, long-range gene regulatory mutations and multiple gene mutations are emerging as new causes of DSDs. Patients with DSDs, their parents and medical staff are confronted with challenging decisions regarding gender assignment, genital surgery and lifelong care. These advances are refining prognostic prediction and systematically improving the diagnosis and long-term management of children with DSDs.
性发育障碍（DSD）以前被称为“间性”疾病，是一种先天性疾病，其染色体、性腺或解剖性别不典型。DSD 的命名和分类已进行了全面修订，强调了这些疾病的遗传病因，并摒弃了贬义词。新术语的应用已广泛普及。影响性腺发育的 DSD 或许是了解最少的。阐明性腺发育的分子机制揭示了 DSD 的新病因，但只有约 20%的患者做出了特定的分子诊断。相反，对 DSD 分子病因的鉴定为性腺发育机制提供了深入了解。对小鼠中 N-乙基-N-亚硝基脲诱变、多基因诊断筛查以及全基因组方法（如比较基因组杂交和新一代测序）的研究，正在加速发现参与性腺发育和 DSD 的基因。此外，长距离基因调控突变和多个基因突变正成为 DSD 的新病因。DSD 患者、其父母和医务人员在性别分配、生殖器手术和终身护理方面面临着具有挑战性的决策。这些进展正在完善预后预测，并系统地改善 DSD 儿童的诊断和长期管理。
