Department of Clinical Genetics and DSD Expert Center Erasmus Medical Center, Erasmus Medical Center, Rotterdam, The Netherlands
Department of Clinical Genetics and DSD Expert Center Erasmus Medical Center, Erasmus Medical Center, Rotterdam, The Netherlands.
J Med Genet. 2020 Sep;57(9):581-589. doi: 10.1136/jmedgenet-2019-106354. Epub 2020 Apr 17.
We present key points from the updated Dutch-Flemish guideline on comprehensive diagnostics in disorders/differences of sex development (DSD) that have not been widely addressed in the current (inter)national literature. These points are of interest to physicians working in DSD (expert) centres and to professionals who come across persons with a DSD but have no (or limited) experience in this area. The Dutch-Flemish guideline is based on internationally accepted principles. Recent initiatives striving for uniform high-quality care across Europe, and beyond, such as the completed COST action 1303 and the European Reference Network for rare endocrine conditions (EndoERN), have generated several excellent papers covering nearly all aspects of DSD. The Dutch-Flemish guideline follows these international consensus papers and covers a number of other topics relevant to daily practice. For instance, although next-generation sequencing (NGS)-based molecular diagnostics are becoming the gold standard for genetic evaluation, it can be difficult to prove variant causality or relate the genotype to the clinical presentation. Network formation and centralisation are essential to promote functional studies that assess the effects of genetic variants and to the correct histological assessment of gonadal material from DSD patients, as well as allowing for maximisation of expertise and possible cost reductions. The Dutch-Flemish guidelines uniquely address three aspects of DSD. First, we propose an algorithm for counselling and diagnostic evaluation when a DSD is suspected prenatally, a clinical situation that is becoming more common. Referral to ultrasound sonographers and obstetricians who are part of a DSD team is increasingly important here. Second, we pay special attention to healthcare professionals not working within a DSD centre as they are often the first to diagnose or suspect a DSD, but are not regularly exposed to DSDs and may have limited experience. Their thoughtful communication to patients, carers and colleagues, and the accessibility of protocols for first-line management and efficient referral are essential. Careful communication in the prenatal to neonatal period and the adolescent to adult transition are equally important and relatively under-reported in the literature. Third, we discuss the timing of (NGS-based) molecular diagnostics in the initial workup of new patients and in people with a diagnosis made solely on clinical grounds or those who had earlier genetic testing that is not compatible with current state-of-the-art diagnostics.
我们提出了更新的荷兰-佛兰芒综合诊断指南中的关键点，这些关键点在当前（国际）文献中尚未广泛涉及。这些要点对在 DSD（专家）中心工作的医生以及遇到 DSD 但在该领域没有（或有限）经验的专业人员感兴趣。荷兰-佛兰芒指南基于国际公认的原则。最近的一些倡议旨在在整个欧洲乃至更远的地方实现统一的高质量护理，例如已经完成的 COST 行动 1303 和欧洲罕见内分泌疾病参考网络（EndoERN），已经产生了许多涵盖 DSD 几乎所有方面的优秀论文。荷兰-佛兰芒指南遵循这些国际共识文件，并涵盖了与日常实践相关的其他一些主题。例如，尽管基于下一代测序（NGS）的分子诊断正在成为遗传评估的黄金标准，但证明变体因果关系或将基因型与临床表现联系起来可能很困难。网络形成和集中对于促进功能研究以评估遗传变异的影响以及对 DSD 患者性腺材料的正确组织学评估至关重要，同时还允许最大限度地利用专业知识和可能降低成本。荷兰-佛兰芒指南独特地解决了 DSD 的三个方面。首先，我们提出了一种在怀疑胎儿存在 DSD 时进行咨询和诊断评估的算法，这种临床情况越来越常见。在这里，向 DSD 团队的超声科医生和产科医生转诊变得越来越重要。其次，我们特别关注不在 DSD 中心工作的医疗保健专业人员，因为他们通常是第一个诊断或怀疑 DSD 的人，但他们不经常接触 DSD ，并且可能经验有限。他们对患者、护理人员和同事的深思熟虑的沟通，以及一线管理和高效转诊协议的可及性至关重要。在产前到新生儿期以及青春期到成年期的精心沟通同样重要，但在文献中相对报道较少。第三，我们讨论了在新患者的初步检查中以及在仅基于临床依据诊断的患者或那些具有与当前最先进诊断不兼容的早期基因检测的患者中进行（基于 NGS 的）分子诊断的时间。
