Frazier Eric, Sabour Ryan, Nguyen Matthew D, Le Dao, Hanna Ramy
University of California - Irvine - School of Medicine, Irvine, CA, USA.
Division of Nephrology, Hypertension, and Kidney Transplantation, Department of Medicine, University of California, Irvine, 3800 Chapman Ave, Suite 6200, Orange, CA, 92868-3298, USA.
BMC Nephrol. 2025 Sep 1;26(1):508. doi: 10.1186/s12882-025-04433-4.
Denys-Drash syndrome (DDS) is defined by early onset nephrotic syndrome rapidly progressing to end stage renal disease (ESRD) before 4 years of age, male pseudohermaphroditism, and Wilms tumor (WT). DDS is associated with mutations in the gene, most commonly in exons 8 or 9. mutations are associated with nephrotic syndrome and renal dysfunction, with an onset in early adulthood.
We present the case of an 18-year-old male with a past medical history of Wilms tumor (status post right nephrectomy, chemotherapy, and radiation during infancy), Denys-Drash syndrome, chronic kidney disease stage 2, and autism spectrum disorder. The patient presented to our clinic with worsening proteinuria discovered secondary to pyelonephritis. Genetic evaluation revealed a mutation, c.388_389insAC (p.Pro130Hisfs*34), complicated by an mutation, c.2698T > A (p.Ser900Thr). Under our care, his worsening proteinuria stabilized, and his estimated glomerular filtration rate (eGFR) remained at 83 mL/min/1.73 m (1.38 mL/s/1.73 m), indicating preserved renal function. We used a multidisciplinary approach to manage this patient through lifestyle modification, regular monitoring, and conservative measures. Surveillance with regular ultrasounds and labs has been key in management. We chose to forgo biopsy because of the risk to the remaining kidney, and we will continue to evaluate the need for an angiotensin-converting enzyme (ACE) inhibitor on the basis of hemodynamic stability.
In this case, we present a patient with delayed nephropathy in the presence of novel and mutations, suggesting the potential for a new genotype‒phenotype relationship of DDS or the attenuation of disease behavior. When diagnostic testing is limited due to increased risk to the patient, we emphasize the need for personalized treatment plans and a multimodal approach with close monitoring in the long-term management of such complicated cases. This case documents novel mutations, highlights the importance of genetic testing, and justifies further investigation into the relationship between genotype and phenotype for patients with mutations contributing to renal pathology.
Not applicable.
The online version contains supplementary material available at 10.1186/s12882-025-04433-4.
迪尼-德拉斯综合征（DDS）的定义为在4岁前迅速进展至终末期肾病（ESRD）的早发性肾病综合征、男性假两性畸形和肾母细胞瘤（WT）。DDS与该基因的突变相关，最常见于外显子8或9。该突变与肾病综合征和肾功能障碍相关，发病于成年早期。
我们报告一例18岁男性患者，既往有肾母细胞瘤病史（婴儿期行右肾切除术、化疗和放疗）、迪尼-德拉斯综合征、慢性肾脏病2期和自闭症谱系障碍。患者因肾盂肾炎继发蛋白尿加重前来我院就诊。基因评估发现一个突变，c.388_389insAC（p.Pro130Hisfs*34），并伴有另一个突变，c.2698T＞A（p.Ser900Thr）。在我们的治疗下，他加重的蛋白尿得到稳定，估计肾小球滤过率（eGFR）维持在83 mL/min/1.73 m²（1.38 mL/s/1.73 m²），表明肾功能保持良好。我们采用多学科方法通过生活方式调整、定期监测和保守措施来管理该患者。定期超声和实验室检查监测是管理的关键。由于对剩余肾脏有风险，我们选择不进行活检，并且我们将根据血流动力学稳定性继续评估是否需要使用血管紧张素转换酶（ACE）抑制剂。
在本病例中，我们报告了一名存在新的突变的迟发性肾病患者，提示可能存在迪尼-德拉斯综合征新的基因型-表型关系或疾病行为的减弱。当由于患者风险增加而诊断性检查受限，我们强调在这类复杂病例的长期管理中需要个性化治疗方案和密切监测的多模式方法。本病例记录了新的突变，强调了基因检测的重要性，并证明有必要进一步研究导致肾脏病理改变的突变患者的基因型与表型之间的关系。
不适用。
在线版本包含可在10.1186/s12882-025-04433-4获取的补充材料。
