Disorders/Differences of Sex Development (DSD) - Translational Research Network

项目总结 性发育障碍/差异(DSD)是一个总括术语，包括先天性疾病，其中 染色体、性腺或解剖性发育是不典型的。DSD是表型不同的， 从生殖器畸形(尿道下裂、隐睾症、阴蒂肥大)到生殖器不明确。 DSD的总体发病率约为1%，并可能导致生育、癌症风险等严重后果 和整个寿命的生活质量。关于临床管理的辩论，特别是性别分配和 生殖器或性腺手术方面的风险有所增加；然而，提供最佳做法的科学数据仍然有限。临床 DSD的护理受到零散的研究议程和缺乏标准化的阻碍，留下了基本的 在DSD病理知识以及治疗方案和预期结果之间的联系方面存在差距。主修 障碍包括对病理生理学的理解上的差距(阻碍准确的诊断分类)， 缺乏对心理社会结果的前瞻性纵向研究及其潜在的缓和影响 生物医学、心理社会和法律因素对医疗决策的影响。 该项目是全球首个前瞻性研究DSD诊断变量途径的项目 以及对心理社会适应的临床管理。这一目标将通过利用 DSD-翻译研究网络(DSD-TRN)的基础设施和强大的协作。网络 由全国12个跨学科医疗团队组成的联盟，与患者一起 利益相关者和生物伦理代表。 我们的指导原则是诊断和治疗方案的循证标准化将是 与更高的明确诊断DSD率相关，减少临床实践中的差异，增强 患者/家庭医疗保健相关体验，并改善患者和他们的心理社会结果 家人。拟议的项目将提供将DSD的医疗质量提高到一定水平所需的证据 观察其他罕见疾病的情况。具体目标包括： 1.遗传学。完善和拓展DSD的分子诊断； 2.心理社会性。确定与以下因素相关的诊断、临床护理以及家庭风险和复原力因素 DSD患者及其家属心理结局的变异性； 3.临床管理的决定因素。确定生物医学、法律和心理社会决定因素 临床管理决策。

PROJECT SUMMARY Disorders/Differences of Sex Development (DSD) is an umbrella term covering congenital conditions in which chromosomal, gonadal, or anatomic sex development is atypical. DSD are phenotypically heterogeneous, ranging from genital malformations (hypospadias, cryptorchidism, clitoral hypertrophy) to genital ambiguity. DSD have a collective incidence of about 1% and can result in serious consequences for fertility, cancer risk and quality of life across the lifespan. Debate over clinical management, in particular gender assignment and genital or gonadal surgery, has intensified; yet scientific data informing best practices remain limited. Clinical care in DSD is hampered by a fragmented research agenda and lack of standardization, leaving fundamental gaps in knowledge of DSD pathology and links between treatment options and desired outcomes. Major obstacles include gaps in understanding of pathophysiology (impeding precise diagnostic categorization), the absence of prospective longitudinal studies of psychosocial outcomes, and the potential moderating influence of biomedical, psychosocial and legal factors on medical decision making. This project is the first of its kind, globally, to prospectively study the variable pathways from DSD diagnosis and clinical management to psychosocial adaptation. This goal will be accomplished by exploiting the infrastructure and robust collaboration of the DSD–Translational Research Network (DSD-TRN). The Network comprises a consortium of 12 interdisciplinary healthcare teams across the nation in conjunction with patient stakeholder and bioethics representation. Our guiding principle is that evidence-based standardization of diagnostic and treatment protocols will be associated with higher rates of definitively diagnosed DSD, reduced variation in clinical practice, enhanced patient/family healthcare-related experiences, and improved psychosocial outcomes for patients and their families. The proposed project will deliver evidence needed to raise the quality of healthcare in DSD to levels observed for other rare diseases. Specific aims include: 1. Genetics. Improving and expanding the molecular diagnosis of DSD; 2. Psychosocial. Identifying diagnostic, clinical care, and family risk and resilience factors associated with variability in psychological outcomes of patients with DSD and their families; 3. Determinants of clinical management. Identifying biomedical, legal, and psychosocial determinants of clinical management decisions.