超声发现胎儿肾脏异常的17q12染色体微缺失综合征三例产前诊断分析

Prenatal diagnosis of 17q12 microdeletion syndrome in fetal renal abnormalities

目的通过分析17q12染色体微缺失综合征胎儿的临床资料，探讨该综合征的产前临床表型及产前诊断方法。方法2013年1月至2017年7月于中国医学科学院北京协和医院就诊行产前超声检查发现胎儿结构异常的孕妇7516例，其中超声发现胎儿单侧或双侧肾脏结构异常者655例（8．71％，655／7516）。7516例孕妇中行染色体微阵列分析（CMA）技术产前诊断者共1370例，其中3例0．40％（3／7516）孕妇的胎儿诊断为17q12染色体微缺失综合征。3例孕妇及其胎儿均行产前诊断及核型分析，并通过亲代荧光原位杂交技术或CMA进行亲代验证。结果3例孕妇的胎儿均于孕中期超声检查提示“双侧肾脏结构的异常”，异常包括肾脏回声增强、多发囊肿及肾盂增宽，其中1例“双侧多发肾囊肿”、2例“双侧肾回声增强”。3例胎儿的染色体核型分析均正常，CMA检测提示均存在17q12染色体区域1．4～1．6Mb的缺失。亲代验证结果显示，3例发生17q12染色体微缺失的胎儿中，2例为新发突变，1例遗传于母亲。经遗传咨询，3例孕妇均选择终止妊娠。结论根据产前胎儿肾脏超声检查的特异性表现，通过产前诊断、染色体核型分析及CMA检测，可在产前诊断超声发现胎儿肾脏异常的17q12染色体微缺失综合征。少部分17q12染色体微缺失综合征患儿甚至遗传于表型正常的亲代，产前遗传咨询往往会相对困难。

Objectives To analyze 3 cases of 17q12 microdeletion syndrome diagnosed prenatally, and to demonstrate clinical phenotype of the syndrome in prenatal setting. Methods From January 2013 to July 2017, 1 370 women received invasive prenatal diagnosis and chromosome microarray analysis （CMA） in Peking Union Medical College Hospital. Among them, 3 fetuses were diagnosed as 17q12 mierodeletion syndrome. All 3 cases were low-risk pregnancies. Abnormal structures in fetal kidney were found in all 3 cases, including 1 case of multiple renal cysts, 2 cases of bilateral hyperechogenic kidneys. These women accepted invasive prenatal diagnosis followed by karyotyping, parental fluorescence in situ hybridization or CMA validation. Results The second and third trimester ultrasound showed that all 3 fetuses had bilateral renal structural abnormalities, including hypereehogenie kidney, multiple cysts and renal pelvis dilatation. The karyotyping of the 3 fetuses were normal. CMA examination showed that each case had 1.4-1.6 Mb deletion in 17q12 region. Two cases were de novo deletion and 1 case was inherited from the mother who had mild symptoms. The 3 women decided to terminate pregnancies after genetic counseling. Conclusion 17q12 microdeletion syndrome is a recurrent chromosome microdeletion syndrome, and the unique phenotype in prenatal setting is the abnormal structure of bilateral kidneys. A few cases of 17ql 2 microdeletion syndrome even inherited normally phenotypical parents, and prenatal genetic counseling of 17q12 microdeletion syndrome is relatively difficult.