儿童扩张型心肌病的临床特点及1例家族性病儿的基因突变分析
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摘要
目的探讨扩张型心肌病(DCM)病儿临床特点及家族性DCM(FDCM)基因突变特点。方法回顾性分析2006年1月—2016年1月于我院住院的49例DCM病儿的临床资料,同时采用Kaplan-Meier法进行生存分析;并分析1例FDCM的基因突变特点。结果 49例DCM病儿中男22例,女27例;年龄<1岁者4例,1~5岁者13例,>5岁者32例;主要症状以及体征为咳嗽、气促、乏力、肝脏增大以及心音低钝,心胸比增大者40例(81.6%)。NYHA心功能分级Ⅲ级以上或Ross评分7分以上者21例(42.9%),29例(59.2%)合并呼吸道感染,无栓塞事件。随访32例,随访时间1~131个月,平均29.25个月,其中死亡13例,5例规律服用强心和利尿药半年~1年后停药,至随访时生活质量可,无明显运动受限;14例坚持规律用药2~5年,日常活动无明显影响。13例死亡病儿均因心力衰竭进行性加重而死亡,无猝死和心脏移植者。DCM病儿1、3和5年生存率分别为68.2%、54.4%和54.4%。1例FDCM病儿基因检测发现DMD c.2473T>G(p.Trp825Gly)突变,为错义突变。结论 DCM以年长儿发病为主,远期预后不良,规范治疗能改善病儿的症状,提高生活质量;DMD c.2473T>G(p.Trp825Gly)有可能为FDCM病儿的致病突变。
Objective To investigate the clinical features of dilated cardiomyopathy(DCM)and gene mutations of familial DCM. Methods A retrospective analysis was performed for the clinical data of 49 children with DCM who were admitted to our hospital from January 2006 to January 2016.The Kaplan-Meier method was used for survival analysis,and gene mutations of one child with familial DCM were analyzed. Results Of all 49 children with DCM,there were 22 boys and 27 girls;4 were aged<1 year,13 were aged 1-5 years,and 32 were aged >5 years.Major symptoms and signs included cough,shortness of breath,weakness,liver enlargement,and muffled heart sound,and of all children,40(81.6%)had an increase in cardiothoracic ratio.Of all 49 children,21(42.9%)had NYHA functional classⅢ or above or Ross score≥7,and 29(59.2%)had respiratory infection;no embolic event was observed.A total of 32 children were followed up for 1-131 months,with a mean follow-up time of 29.25 months,and among these children,13 died;5 were given regular administration of cardiotonic drugs and diuretics for half a year to one year and had good quality of life at the end of follow-up,with little movement limitation;14 adhered to regular administration for 2-5 years and had no significant influence on daily activities.All 13 children died of progressive exacerbation of heart failure,and there were no cases of sudden death or heart transplantation.The 1-,3-,and 5-year survival rates of children with DCM were68.2%,54.4%,and 54.4%,respectively.One child with familial DCM was found to have a missense mutation of DMD,c.2473 T>G(p.Trp825 Gly). Conclusion DCM is often observed in older children and has poor long-term prognosis.Standardized treatment can improve children's symptoms and quality of life.DMD c.2473 T>G(p.Trp825 Gly)may be a pathogenic mutation in children with familial DCM.
Objective To investigate the clinical features of dilated cardiomyopathy(DCM)and gene mutations of familial DCM. Methods A retrospective analysis was performed for the clinical data of 49 children with DCM who were admitted to our hospital from January 2006 to January 2016.The Kaplan-Meier method was used for survival analysis,and gene mutations of one child with familial DCM were analyzed. Results Of all 49 children with DCM,there were 22 boys and 27 girls;4 were aged<1 year,13 were aged 1-5 years,and 32 were aged >5 years.Major symptoms and signs included cough,shortness of breath,weakness,liver enlargement,and muffled heart sound,and of all children,40(81.6%)had an increase in cardiothoracic ratio.Of all 49 children,21(42.9%)had NYHA functional classⅢ or above or Ross score≥7,and 29(59.2%)had respiratory infection;no embolic event was observed.A total of 32 children were followed up for 1-131 months,with a mean follow-up time of 29.25 months,and among these children,13 died;5 were given regular administration of cardiotonic drugs and diuretics for half a year to one year and had good quality of life at the end of follow-up,with little movement limitation;14 adhered to regular administration for 2-5 years and had no significant influence on daily activities.All 13 children died of progressive exacerbation of heart failure,and there were no cases of sudden death or heart transplantation.The 1-,3-,and 5-year survival rates of children with DCM were68.2%,54.4%,and 54.4%,respectively.One child with familial DCM was found to have a missense mutation of DMD,c.2473 T>G(p.Trp825 Gly). Conclusion DCM is often observed in older children and has poor long-term prognosis.Standardized treatment can improve children's symptoms and quality of life.DMD c.2473 T>G(p.Trp825 Gly)may be a pathogenic mutation in children with familial DCM.
引文
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[7]中华心血管病杂志编辑委员会心肌炎心肌病对策专题组.关于成人急性病毒性心肌炎诊断参考标准和采纳世界卫生组织及国际心脏病学会联合会工作组关于心肌病定义和分类的意见[J].中华心血管病杂志,1999,16(6):307-308.
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[11]段庆宁,王凤鸣,赵乃峥,等.原发性扩张型心肌病96例患儿长期随访[J].实用儿科临床杂志,2011,26(13):997-1000.
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[13]SILVA M J,PINTO F J.Clinical use of multimodality imaging in the assessment of dilated cardiomyopathy[J].Heart,2015,101(7):565-572.
[14]ALVAREZ J A,ORAV E J,WILKINSON J D,et al.Competing risks for death and cardiac transplantation in children with dilated cardiomyopathy:Results from the pediatric cardiomyopathy registry[J].Circulation,2011,124(7):814-823.
[15]李运泉,周福军,陈国桢,等.小儿心肌病临床和生存分析[J].实用儿科临床杂志,2008,23(17):1354-1356.
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[18]YAJIMA T,KNOWLTON K U.Viral myocarditis:From the perspective of the virus[J].Circulation,2009,119(19):2615-2624.
[19]SAGAR S,LIU P P,COOPER L J.Myocarditis[J].Lancet,2012,379(9817):738-747.
[20]曹敏.炎症性扩张型心肌病免疫抑制治疗的随机化安慰剂对照试验:2年随访结果[J].国外医学:心血管疾病分册,2002,29(1):64.
[21]YOSHIKAWA T,BABA A,AKAISHI M,et al.Immunoadsorption therapy for dilated cardiomyopathy using tryptophan column-A prospective,multicenter,randomized,within-patient and parallel-group comparative study to evaluate efficacy and safety[J].J Clin Apher,2016,31(6):535-544.
[22]LAKDAWALA N K,WINTERFIELD J R,FUNKE B H.Dilated cardiomyopathy[J].Circ Arrhythm Electrophysiol,2013,6(1):228-237.
[23]杨杰孚,廖玉华,袁瞡,等.中国扩张型心肌病诊断和治疗指南[J].临床心血管病杂志,2018,34(5):421-434.
[24]MESTRONI L,BRUN F,SPEZZACATENE A,et al.Gene-tic causes of dilated cardiomyopathy[J].Prog Pediatr Cardiol,2014,37(1-2):13-18.
[25]ZHAO C M,SUN S,SONG H M,et al.TBX20loss-offunction mutation associated with familial dilated cardiomyopathy[J].Clin Chem Lab Med,2016,54(2):325-332.
[26]ZHOU Y M,DAI X Y,QIU X B,et al.HAND1loss-offunction mutation associated with familial dilated cardiomyopathy[J].Clin Chem Lab Med,2016,54(7):1161-1167.
[27]梁华生,张黔桓,陈泗林.扩张型心肌病致病基因的研究进展[J].国际心血管病杂志,2016,43(1):22-24.
[28]刘剑,田野,孟繁超.X-连锁扩张型心肌病患者杜兴氏肌营养不良基因突变分析及临床评价[J].中国实用内科杂志,2004(1):14-16.
[29]NAKAMURA A.X-Linked dilated cardiomyopathy:A cardiospecific phenotype of dystrophinopathy[J].Pharmaceuticals(Basel),2015,8(2):303-320.
[30]CHAMBERLAIN R C,SMITH E C,CAMPBELL M J.Novel rod domain duplication in dystrophin resulting in X-Linked dilated cardiomyopathy[J].Pediatr Neurol,2015,53(5):439-441.
[31]HOOGERWAARD E M,BAKKER E,IPPEL P F,et al.Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the netherlands:a cohort study[J].Lancet,1999,353(9170):2116-2119.
[32]中华医学会儿科学分会心血管学组,中华儿科杂志编辑委员会.儿童心肌病基因检测建议[J].中华儿科杂志,2013,51(8):595-597.
[33]杨世伟,秦玉明.儿童心肌病遗传学研究进展与精准诊断展望[J].中国实用儿科杂志,2016,31(8):574-578.
[34]王怡璐,宋雷,康连鸣.肥厚型心肌病——心血管疾病精准医疗离我们有多远[J].中国医学前沿杂志(电子版),2016,8(5):8-15.
[2]MIGLIORE F,ZORZI A,MICHIELI P,et al.Prevalence of cardiomyopathy in Italian asymptomatic children with electrocardiographic T-wave inversion at preparticipation screening[J].Circulation,2012,125(3):529-538.
[3]郭潇,张健.儿童扩张型心肌病的病因及预后[J].中国循环杂志,2013,28(5):396-398.
[4]TOWBIN J A,LOWE A M,COLAN S D,et al.Incidence,causes,and outcomes of dilated cardiomyopathy in children[J].JAMA,2006,296(15):1867-1876.
[5]DAUBENEY P E,NUGENT A W,CHONDROS P,et al.Clinical features and outcomes of childhood dilated cardiomyopathy:Results from a national population-based study[J].Circulation,2006,114(24):2671-2678.
[6]中华医学会心血管病学分会,中华心血管病杂志编辑委员会,中国心肌病诊断与治疗建议工作组.心肌病诊断与治疗建议[J].中华心血管病杂志,2007,35(1):5-16.
[7]中华心血管病杂志编辑委员会心肌炎心肌病对策专题组.关于成人急性病毒性心肌炎诊断参考标准和采纳世界卫生组织及国际心脏病学会联合会工作组关于心肌病定义和分类的意见[J].中华心血管病杂志,1999,16(6):307-308.
[8]LIPSHULTZ S E,SLEEPER L A,TOWBIN J A,et al.The incidence of pediatric cardiomyopathy in two regions of the United States[J].N Engl J Med,2003,348(17):1647-1655.
[9]韩燕燕,聂抒,孙景辉,等.小儿扩张型心肌病62例临床分析[J].中华全科医师杂志,2009,8(12):899-900.
[10]章旭,黄美蓉,陈树宝,等.儿童心肌病诊断治疗10年回顾[J].临床儿科杂志,2011,29(4):345-348.
[11]段庆宁,王凤鸣,赵乃峥,等.原发性扩张型心肌病96例患儿长期随访[J].实用儿科临床杂志,2011,26(13):997-1000.
[12]NUGENT A W,DAUBENEY P E,CHONDROS P,et al.The epidemiology of childhood cardiomyopathy in Australia[J].N Engl J Med,2003,348(17):1639-1646.
[13]SILVA M J,PINTO F J.Clinical use of multimodality imaging in the assessment of dilated cardiomyopathy[J].Heart,2015,101(7):565-572.
[14]ALVAREZ J A,ORAV E J,WILKINSON J D,et al.Competing risks for death and cardiac transplantation in children with dilated cardiomyopathy:Results from the pediatric cardiomyopathy registry[J].Circulation,2011,124(7):814-823.
[15]李运泉,周福军,陈国桢,等.小儿心肌病临床和生存分析[J].实用儿科临床杂志,2008,23(17):1354-1356.
[16]TSIRKA A E,TRINKAUS K,CHEN S C,et al.Improved outcomes of pediatric dilated cardiomyopathy with utilization of heart transplantation[J].J Am Coll Cardiol,2004,44(2):391-397.
[17]HSU D T,CANTER C E.Dilated cardiomyopathy and heart failure in children[J].Heart Fail Clin,2010,6(4):415-432.
[18]YAJIMA T,KNOWLTON K U.Viral myocarditis:From the perspective of the virus[J].Circulation,2009,119(19):2615-2624.
[19]SAGAR S,LIU P P,COOPER L J.Myocarditis[J].Lancet,2012,379(9817):738-747.
[20]曹敏.炎症性扩张型心肌病免疫抑制治疗的随机化安慰剂对照试验:2年随访结果[J].国外医学:心血管疾病分册,2002,29(1):64.
[21]YOSHIKAWA T,BABA A,AKAISHI M,et al.Immunoadsorption therapy for dilated cardiomyopathy using tryptophan column-A prospective,multicenter,randomized,within-patient and parallel-group comparative study to evaluate efficacy and safety[J].J Clin Apher,2016,31(6):535-544.
[22]LAKDAWALA N K,WINTERFIELD J R,FUNKE B H.Dilated cardiomyopathy[J].Circ Arrhythm Electrophysiol,2013,6(1):228-237.
[23]杨杰孚,廖玉华,袁瞡,等.中国扩张型心肌病诊断和治疗指南[J].临床心血管病杂志,2018,34(5):421-434.
[24]MESTRONI L,BRUN F,SPEZZACATENE A,et al.Gene-tic causes of dilated cardiomyopathy[J].Prog Pediatr Cardiol,2014,37(1-2):13-18.
[25]ZHAO C M,SUN S,SONG H M,et al.TBX20loss-offunction mutation associated with familial dilated cardiomyopathy[J].Clin Chem Lab Med,2016,54(2):325-332.
[26]ZHOU Y M,DAI X Y,QIU X B,et al.HAND1loss-offunction mutation associated with familial dilated cardiomyopathy[J].Clin Chem Lab Med,2016,54(7):1161-1167.
[27]梁华生,张黔桓,陈泗林.扩张型心肌病致病基因的研究进展[J].国际心血管病杂志,2016,43(1):22-24.
[28]刘剑,田野,孟繁超.X-连锁扩张型心肌病患者杜兴氏肌营养不良基因突变分析及临床评价[J].中国实用内科杂志,2004(1):14-16.
[29]NAKAMURA A.X-Linked dilated cardiomyopathy:A cardiospecific phenotype of dystrophinopathy[J].Pharmaceuticals(Basel),2015,8(2):303-320.
[30]CHAMBERLAIN R C,SMITH E C,CAMPBELL M J.Novel rod domain duplication in dystrophin resulting in X-Linked dilated cardiomyopathy[J].Pediatr Neurol,2015,53(5):439-441.
[31]HOOGERWAARD E M,BAKKER E,IPPEL P F,et al.Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the netherlands:a cohort study[J].Lancet,1999,353(9170):2116-2119.
[32]中华医学会儿科学分会心血管学组,中华儿科杂志编辑委员会.儿童心肌病基因检测建议[J].中华儿科杂志,2013,51(8):595-597.
[33]杨世伟,秦玉明.儿童心肌病遗传学研究进展与精准诊断展望[J].中国实用儿科杂志,2016,31(8):574-578.
[34]王怡璐,宋雷,康连鸣.肥厚型心肌病——心血管疾病精准医疗离我们有多远[J].中国医学前沿杂志(电子版),2016,8(5):8-15.