Denys-Drash综合征三例临床病理特点

Clinical and pathological features of Denys-Drash syndrome： report of 3 cases

目的探讨Denys—Drash综合征（DDS）的临床病理特征，以加深对DDS的认识。方法总结2009至2011年诊治3例DDS患儿的临床病理特点和WT1检测结果，并结合文献复习。结果3例DDS，例1、例2为核型46XX、外生殖器正常女性，例3为男性伴双侧腹股沟隐睾。肾病起病年龄分别为1岁9个月、2岁4个月及3个月。例2、例3激素治疗无效。例1使用他克莫司，血浆白蛋白、胆固醇有改善，尿蛋白无缓解。例2用环孢素A、他克莫司蛋白尿均能缓解；现4岁9个月，蛋白尿缓解，肾功能正常。3例均是右肾单侧Wilms瘤，残肾病理均为弥漫系膜硬化。WT1检测：例1为外显子9的c．1213C〉G错义突变，为新突变；例2、例3分别为e．1168C〉T无义突变和c．1130A〉T错义突变。结论DDS肾病临床表现变化较大，起病多较早，肾衰竭常在4岁以前出现，少数起病及肾衰竭出现较晚。其蛋白尿对激素治疗无效，但对钙神经素抑制剂环孢素A有效；本研究2例患儿使用他克莫司亦有效。DDS多因WT1突变所致，肾脏病理主要为弥漫系膜硬化。

Objective To study the clinical and pathological features of Denys-Drash syndrome （DDS）. Method Three DDS eases who were treated in our department from December 2009 to June 2011 were subjected to this study by reviewing of literature. Result Both case 1 and case 2 were female, with karyotype 46, XX. Case 3 was male with bilateral cryptorchidism. The ages of nephropathy onset of the three cases were 1 year and 9 months, 2 years and 8 moths, and 3 months respectively. Proteinuria in case 2 and case 3 were evidenced to be resistant to steroid. Case 1 was partially responsive to tacrolimus, plasma albumin and cholesterol were improved, although proteinuria was persistent after Taerolimus was administered. Remission was achieved in case 2 after administration of cyclosporine A and later taerolimus, and her renal function remains normal till present （4 years and 9 months）. Residue renal histology revealed diffused mesangial sclerosis （ DMS ） in all three patients. All of the three patients had developed right unilateral Wilms tumor. A novel WTI missense mutation exon 9 c. 1213C 〉 G was detected in case 1. WT1 exon 9 c. 1168C 〉 T nonsense mutation and exon 8 c. 1130A 〉 T missense mutation were detected in case 2 and case 3, respectively. Conclusion The clinical manifestation of nephropathy in DDS is variable. The majority present with early onset nephropathy and reach renal failure before the age of 4 years. But in a few patients, nephropathy can also be present much later and progress slowly. Proteinuria in DDS is resistant to steroid but is responsive to calcineurin inhibitors, including Cyclosporine A. The effectiveness of tacrolimus was also observed in this study. DDS is evidently caused by WT1 mutation. DMS is the characteristic renal pathological change in DDS.