SCN5A基因突变致扩张型心肌病伴房室传导阻滞的家系调查

Pedigree investigation of dilated cardiomyopathy and atrioventricular block caused by SCN5A gene mutation

目的:通过对已发现的心脏钠通道基因SCN5A A1180V突变相关的扩张型心肌病(dilated cardiomyopathy,DCM)伴房室传导阻滞(atrioventricular block,AVB)家系进行随访,分析SCN5A基因A1180V突变致DCM的临床特征及病情演变特点,为制订该类突变携带者临床防治策略提供依据。方法:根据2007年初次发现该家系和2012年随访资料,于2021年对家系中健在的6名A1180V突变携带者及7名非突变携带者再次询问病史,予以12导联心电图、超声心动图检查。分析该家系中10名突变携带者(含3名已故突变携带者及1名此次未参加随访者),7名非突变携带者及1名已故的基因型不详成员的临床资料。结果:该家系中SCN5A A1180V突变携带者发病首发症状常为Ⅰ度AVB,平均诊断年龄为(36±4.42)岁,多数逐渐进展为Ⅲ度AVB伴心脏扩大。2012年后有1名年长携带者猝死,4名携带者已由Ⅰ度AVB进展为Ⅲ度AVB。先证者的3名子女均为携带者,2021年已出现Ⅲ度AVB,并植入起搏器。虽然这3名携带者已达其父亲发生DCM的年龄,但此次随访心脏功能均未见明显异常,提示突变携带者出现DCM表型延缓。先证者胞弟家的3名女儿携带突变,在2012年随访时心电图和超声心动图均无异常,此次2名出现Ⅰ度AVB;另一名出现Ⅲ度AVB,考虑其病情加重与重体力劳动有关。结论:SCN5A基因A1180V突变、遗传背景和环境因素对DCM表型共同发挥作用;控制心率和减少体力劳动能延缓该家系A1180V突变携带者疾病表型的出现及进展。

Objective: To explore the clinical characteristics, prevention, and treatment strategy for SCN5 A A1180 V mutation carriers by following up a family displaying dilated cardiomyopathy(DCM) and atrioventricular block(AVB).Methods: According to the first discovery of the family in 2007 and the follow-up data in 2012, the medical history of 6 A1180 V mutation carriers and 7 non mutation carriers in the family were followed up by medical history inquiring in 2021, and 12-lead electrocardiogram and echocardiography were performed. Clinical data of 10 mutation carriers(including 3 dead mutation carriers and 1 person who did not participate in the follow-up), 7 non mutation carriers and 1 dead member with unknown genotype were analyzed.Results: In this family, the first symptom of SCN5 A A1180 V mutation carrier was usually degree Ⅰ AVB(mean age at diagnosis was [36±4.42] years), and most gradually progressed to degree Ⅲ AVB and DCM. After 2012, one old carrier had suffered sudden cardiac death, and four carriers had progressed to degree Ⅲ AVB from degree Ⅰ AVB. Three children of the proband had implanted pacemaker because of degree Ⅲ AVB, but they had no cardiac dysfunction even though they were at the age when their father had DCM, indicating the phenotype of DCM in mutation carriers was delayed. The three daughters of the proband’s younger brother manifested normal ECG and echocardiography in 2012. However, two had degree Ⅰ AVB and one had degree Ⅲ AVB in 2021, the exacerbation might be related to heavy physical labour.Conclusions: A1180 V mutation of SCN5 A, genetic background, and environmental factors play a mutual role in the phenotype of DCM, and the prevention and treatment strategy of controlling heart rate and reducing physical labor could delay the appearance and progression of the disease phenotype for A1180 V mutation carriers in this family.