基因检测在儿童非肌小节肥厚性心肌病诊断中的价值

VALUE OF GENE DETECTION IN DIAGNOSIS OF NON-SARCOMERE HYPERTROPHIC CARDIOMYOPATHY IN CHILDREN

目的探讨儿童非肌小节肥厚性心肌病(HCM)的临床特征和基因检测的诊断价值。方法回顾性分析2016年9月—2018年4月于我院治疗的以HCM为首发表现的3例NOONAN综合征、5例糖原累积病Ⅱ型及1例LEOPARD综合征病儿的临床特点和基因检测结果。结果临床表现方面,9例病儿均存在反复呼吸道感染、生长发育迟缓及特殊面容,LEOPARD综合征病儿皮肤可见散在雀斑样痣;7例病儿肌力减低;肝功能损害5例,肌酸激酶异常4例。糖原累积病Ⅱ型病儿中4例心电图表现为PR间期缩短、高大QRS波群及巨大倒置T波。超声心动图发现梗阻性HCM 4例,非梗阻性HCM 5例。5例病儿进行酸性α-葡糖苷酶(GAA)活性测定均提示GAA活性缺乏。基因检测结果发现3例NOONAN综合征分别为RAF1基因、KRAS基因新生突变及PTPN11基因常染色体显性遗传;5例糖原累积病Ⅱ型的GAA基因均为复合杂合突变;1例LEOPARD综合征为RAF1基因新生突变。预后方面,3例糖原累积病Ⅱ型病儿规律阿糖苷酶α替代治疗,均因呼吸衰竭死亡;余6例病儿对症治疗,门诊随访中。结论非肌小节HCM临床上表现多样,易引起漏诊和误诊,临床工作中需注意其临床特征,通过特殊酶学检查和基因测定可明确诊断。

Objective To investigate the clinical features of non-sarcomere hypertrophic cardiomyopathy(HCM)in children and the diagnostic value of gene detection. Methods A retrospective analysis was performed for the clinical features and gene detection results of 3 patients with NOONAN syndrome,5 patients with glycogen storage disease typeⅡ,and 1 patient with LEOPARD syndrome with HCM as the initial manifestation,who were treated in our hospital from September 2016 to April 2018.Results As for clinical manifestations,all 9 patients had recurrent respiratory tract infection,developmental delay,and unusual facies;the patient with LEOPARD syndrome had sporadic lentiginous nevi;7 patients had reduced muscle strength;5 patients had liver dysfunction and 4 patients had abnormal creatine kinase.Among the patients with glycogen storage disease typeⅡ,4 had shortened PR interval,high QRS complex,and giant T-wave inversion on electrocardiogram.Echocardiography found obstructive HCM in 4 patients and non-obstructive HCM in 5 patients.Acid alpha-D-glucosidase(GAA)activity assay was performed for 5 patients and the results suggested a lack of GAA activity.Gene detection showed de novo mutations in the RAF1 and KRAS genes and PTPN11 autosomal dominant inheritance in 3 patients with NOONAN syndrome,compound heterozygous mutations in the GAA gene in 5 patients with glycogen storage disease typeⅡ,and de novo mutation in the RAF1 gene in the patient with LEOPARD syndrome.As for prognosis,3 patients with glycogen storage disease typeⅡwere given glucosidase alpha replacement therapy re-gularly and they all died of respiratory failure;the other 6 patients were given symptomatic treatment and were still followed up in the outpatient service. Conclusion Non-sarcomere HCM have diverse clinical manifestations,which may lead to missed diagnosis and misdiagnosis.It is necessary to pay attention to its clinical features and special enzyme examinations and gene detection can be used to make a definite diagnosis.