Long-term outcome in a case series of Denys-Drash syndrome
Long-term outcome in a case series of Denys-Drash syndrome
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DOI：
10.1093/ckj/sfz022
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发表时间：
2019-12-01
影响因子：
4.6
通讯作者：
Ariceta, Gema
中科院分区：
文献类型：
--
作者：
Roca, Neus;Munoz, Marina;Ariceta, Gema
背景资料。Denys-Drash综合征(DDS)是一种罕见的疾病，由WT1基因外显子8和9突变引起。它的特点是与早发性类固醇抵抗型肾病综合征(SRNS)、肾母细胞瘤有关，在某些患者中还与两性障碍有关，并增加发生性母细胞瘤的风险。关于DDS患者的长期预后，已发表的数据很少。本研究的目的是报告我们的经验。数据收集自1996年至2017年确诊为DDS的5名儿童(3名男孩)。这些患者的平均随访时间为16年。患者在肾活检时表现为SRNS和弥漫性系膜硬化症。所有患者均为高血压，并进展为终末期肾病，开始透析的平均年龄为28个月。3例患者在确诊后9个月出现肾母细胞瘤，接受了肾切除和化疗。所有五名患者都接受了肾移植。所有患者移植后SRNS均未复发，移植肾存活率与本方案中其他肾移植受者相似。这三个男孩都有不明确的生殖器和隐睾症，但确认为男性核型(46，XY)。一名女孩表现为性腺发育不全，而另一名女孩的卵巢组织和外生殖器正常。两名女孩均为女性核型(46，XX)。未发现性腺母细胞瘤。由于SRNS的低患病率、所需的特殊治疗方法以及早期发现肾母细胞瘤，因此早期识别DDS是至关重要的。关于长期结果的数据很少。
Background. Denys-Drash syndrome (DDS) is a rare disease caused by mutations in exons 8 and 9 of the WT1 gene. It is characterized by the association of early onset steroid-resistant nephrotic syndrome (SRNS), Wilms' tumour and, in some patients, intersex disorders, with increasing risk of gonadoblastoma. There are few published data concerning the long-term outcome of patients with DDS. The aim of this study was to report our experience.Methods. Data were collected from five children (three boys) with confirmed DDS diagnosed from 1996 to 2017. The mean follow-up of these patients was 16 years.Results. The patients presented with SRNS and diffuse mesangial sclerosis at renal biopsy. All patients were hypertensive and progressed to end-stage kidney disease, initiating dialysis at a mean age of 28 months. Three patients developed Wilms' tumour 9 months after the SRNS was identified, which was treated by nephrectomy and chemotherapy. All five patients received kidney transplantation. SRNS did not recur after transplantation in any of the patients and graft survival was similar to that of other kidney transplant recipients in our programme. All three boys had ambiguous genitalia and cryptorchidism but a confirmed male karyotype (46, XY). One girl presented with gonadal agenesis, whereas the other one had normal female ovarian tissue and external genitalia. Both girls had a female karyotype (46, XX). Gonadoblastoma was not observed at any case.Conclusions. Early DDS recognition in patients with SRNS is crucial due to its low prevalence, the specific treatment approach required and early detection of Wilms' tumour. Few data are available regarding long-term outcomes.