Division of Endocrinology, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Division of Genetics, Genomics, and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Am J Med Genet A. 2024 Feb;194(2):351-357. doi: 10.1002/ajmg.a.63377. Epub 2023 Oct 3.
Establishing an early and accurate genetic diagnosis among patients with differences of sex development (DSD) is crucial in guiding the complex medical and psychosocial care they require. Genetic testing routinely utilized in clinical practice for this population is predicated upon physical exam findings and biochemical and endocrine profiling. This approach, however, is inefficient and unstandardized. Many patients with DSD, particularly those with 46,XY DSD, never receive a molecular genetic diagnosis. Rapid genome sequencing (rGS) is gaining momentum as a first-tier diagnostic instrument in the evaluation of patients with DSD given its ability to provide greater diagnostic yield and timely results. We present the case of a patient with nonbinary genitalia and systemic findings for whom rGS identified a novel variant of the WT1 gene and resulted in a molecular diagnosis within two weeks of life. This timeframe of diagnosis for syndromic DSD is largely unprecedented at our institution. Rapid GS expedited mobilization of a multidisciplinary medical team; enabled early understanding of clinical trajectory; informed planning of medical and surgical interventions; and guided individualized psychosocial support provided to the family. This case highlights the potential of early rGS in transforming the evaluation and care of patients with DSD.
在差异性别发育（DSD）患者中尽早进行准确的基因诊断对于指导他们所需的复杂医疗和心理社会护理至关重要。临床实践中常规用于该人群的基因检测基于体格检查结果以及生化和内分泌分析。然而，这种方法效率低下且不规范。许多 DSD 患者，特别是那些 46,XY DSD 患者，从未接受过分子遗传学诊断。鉴于快速基因组测序（rGS）能够提供更高的诊断率和及时的结果，它作为 DSD 患者评估的一线诊断工具正在获得动力。我们介绍了一名具有非二元生殖器和全身表现的患者的病例，rGS 在此患者中鉴定出 WT1 基因的一种新型变体，并在出生后两周内得出了分子诊断结果。在我们机构，这种综合征性 DSD 的诊断时间范围在很大程度上是前所未有的。快速 GS 加快了多学科医疗团队的动员；使我们能够及早了解临床轨迹；为医疗和手术干预的计划提供信息；并指导为家庭提供个性化的心理社会支持。这个病例突出了早期 rGS 在改变 DSD 患者评估和护理方面的潜力。
