胎儿心脏横纹肌瘤的超声诊断及基因学检测

Echocardiographic diagnosis and genotyping of antenatal cardiac rhabdomyoma

目的分析心脏横纹肌瘤的胎儿超声心动图特点，及联合基因检测诊断结节性硬化症（tuberous sclerosis complex，TSC）的意义。方法2013年1月至2015年9月，共7559例胎儿于首都医科大学附属北京安贞医院胎儿心脏病母胎医学会诊中心就诊，其中10例疑似心脏横纹肌瘤并取得生物学标本的胎儿纳入分析。8例引产终止妊娠者取引产儿心肌组织、三角肌组织或脐带组织，2例分娩者取新生儿外周血，应用二代测序——目标区域捕获技术对TSC1及TSC2基因外显子及其邻近±10bp内含子区进行测序，并对父母进行Sanger验证，寻找其致病基因。结果10例胎儿家族性发病4例，散发性发病6例。超声心动图显示心脏单发实性占位2例；多发实性占位8例。2例单发性占位胎儿未检出TSC1或TSC2基因突变；余8例检出TSC1和／或TSC2基因突变，其中已知致病突变2例（家族性），新发疑似致病突变4例（2例家族性），1例临床意义不明突变，1例疑似良性变异。结论胎儿期发现的心脏实性占位多为TSC，常表现为多发实性结节。家族性发病更易于发现致病或疑似致病基因突变。

Objective To analyze the echocardiographic features of antenatal cardiac rhabdomyoma, and the significance of genotyping in tuberous sclerosis complex （TSC）. Methods From January 2013 to September 2015, 10 out of 7 559 fetal cases tested in the Maternal-Fetal Medical Center for Fetal Heart Diseases, Anzhen Hospital who were suspected of cardiac rhabdomyoma, with biological specimens, were enrolled in the analysis. Heart tissue, umbilical cord, deltoid or other tissues were collected from eight fetuses of terminated pregnancy, and peripheral blood was collected from the two newborns and their parents. Next generation sequencing using target area capture technology was performed to sequence TSC1 and TSC2 gene exon intron and its adjacent l0 bp, and Sanger sequence was confirmed in parents. Results Among the 10 fetuses, four were familial and the other six were sporadic cases. Echocardiography revealed a single tumor in two fetuses, and multiple tumors in eight fetuses. No mutation of TSC1 or TSC2 gene was detected in the two fetuses with isolated tumors, while mutations were found in the other eight fetuses, including two cases of known mutations and both were familial, four cases of new suspected mutations （two were familial）, one with unknown clinical significance and one was suspected of benign variation. Conelusions Most prenatal cardiac tumors detected by echocardiography are TSC, and often manifested as multiple solid nodules. Pathogenic or suspected pathogenic gene mutations are more common in familial diseases.