儿童肥厚型心肌病的病因学进展
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摘要
儿童肥厚型心肌病(HCM)是一类常见的心血管遗传基因异常疾病,多数为单基因常染色体显性遗传性心肌病,也不排除其他遗传方式。HCM以心室对称性或非对称性肥厚为主要特征,组织病理学特点为心肌细胞肥大、排列紊乱以及纤维化。一般将儿童HCM分为原发性和继发性两种,原发性以编码肌小节蛋白基因突变为主要病因,非肌小节蛋白基因突变次之;其中肌小节性HCM以MYH7、MYBPC3、TNNT等基因突变为主。继发性病因包括肥胖、糖尿病母亲婴儿、运动员综合征、异常激素增高或药物诱发等。
Hypertrophic cardiomyopathy(HCM)in children is a kind of common cardiovascular genetic abnormalities disease,mostly single gene autosomal dominant inherited cardiomyopathy,although it does not exclude other genetic patterns. The main features of HCM are symmetrical or asymmetrical ventricular hypertrophy,and histopathological characteristics are myocyte hypertrophy,being disorganized,and fibrosis. Generally,HCM in children is divided into primary and secondary types. Mutation of sarcomere protein gene is the main cause of primary cardiomyopathy,followed by mutation of non-sarcomere protein gene.Mutation of MYH7,MYBPC3,TNNT and other genes are the main causes of sarcomere HCM. Secondary causes include obesity,diabetic mothers and babies,athlete syndrome,abnormal hormone elevation or drug-induced and so on.
Hypertrophic cardiomyopathy(HCM)in children is a kind of common cardiovascular genetic abnormalities disease,mostly single gene autosomal dominant inherited cardiomyopathy,although it does not exclude other genetic patterns. The main features of HCM are symmetrical or asymmetrical ventricular hypertrophy,and histopathological characteristics are myocyte hypertrophy,being disorganized,and fibrosis. Generally,HCM in children is divided into primary and secondary types. Mutation of sarcomere protein gene is the main cause of primary cardiomyopathy,followed by mutation of non-sarcomere protein gene.Mutation of MYH7,MYBPC3,TNNT and other genes are the main causes of sarcomere HCM. Secondary causes include obesity,diabetic mothers and babies,athlete syndrome,abnormal hormone elevation or drug-induced and so on.
引文
[1]马沛然,汪翼.小儿心肌病分类的建议和说明[J].中华儿科杂志,2012,50(6):472-474.
[2]Rowin EJ,Orfanos A,Estes N,et al.Occurrence and natural history of clinically silent episodes of atrial fibrillation in hypertrophic cardiomyopathy[J].Am J Cardiol,2017,119(11):1862-1865.
[3]Helms AS,Day SM.Hypertrophic cardiomyopathy:single gene disease or complex trait?[J].Eur Heart J,2016,37(23):1823-1825.
[4]Richard P,Charron P,Carrier L,et al.Hypertrophic cardiomyopathy:distribution of disease genes,spectrum of mutations,and implications for a molecular diagnosis strategy[J].Circulation,2003,107(17):2227-2232.
[5]Erdmann J,Daehmlow S,Wischke S,et al.Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy[J].Clin Genet,2003,64(4):339-349.
[6]Millat G,Bouvagnet P,Chevalier P,et al.Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy[J].Eur J Med Genet,2010,53(5):261-267.
[7]Kaski JP,Syrris P,Esteban MT,et al.Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy[J].Circ Cardiovasc Genet,2009,2(5):436-441.
[8]Kimura A,Harada H,Park JE,et al.Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy[J].Nat Genet,1997,16(4):379-382.
[9]Thierfelder L,Watkins H,MacRae C,et al.Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy:a disease of the sarcomere[J].Cell,1994,77(5):701-712.
[10]Farrell E,Armstrong AE,Grimes AC,et al.Transcriptome analysis of cardiac hypertrophic growth in MYBPC3-Null mice suggests early responders in hypertrophic remodeling[J].Front Physiol,2018,9:1442.
[11]Claes GR,van Tienen FH,Lindsey P,et al.Hypertrophic remodelling in cardiac regulatory myosin light chain(MYL2)founder mutation carriers[J].Eur Heart J,2016,37(23):1815-1822.
[12]Mirabel M,Damy T,Donal E,et al.Influence of centre expertise on the diagnosis and management of hypertrophic cardiomyopathy:A study from the French register of hypertrophic cardiomyopathy(REMY)[J].Int J Cardiol,2019,275:107-113.
[13]Ehsan M,Kelly M,Hooper C,et al.Mutant muscle LIM protein C58G causes cardiomyopathy through protein depletion[J].J Mol Cell Cardiol,2018,121:287-296.
[14]Vanninen S,Leivo K,Seppala EH,et al.Heterozygous junctophilin-2(JPH2)p.(Thr161Lys)is a monogenic cause for HCMwith heart failure[J].PLoS One,2018,13(9):e203422.
[15]Walsh R,Buchan R,Wilk A,et al.Defining the genetic architecture of hypertrophic cardiomyopathy:re-evaluating the role of non-sarcomeric genes[J].Eur Heart J,2017,38(46):3461-3468.
[16]Sanderson S,Green A,Preece MA,et al.The incidence of inherited metabolic disorders in the West Midlands,UK[J].Arch Dis Child,2006,91(11):896-899.
[17]Chatterjee A,Seyfferth J,Lucci J,et al.MOF acetyl transferase regulates transcription and respiration in mitochondria[J].Cell,2016,167(3):722-738.
[18]Prendiville TW,Gauvreau K,Tworog-Dube E,et al.Cardiovascular disease in Noonan syndrome[J].Arch Dis Child,2014,99(7):629-634.
[19]Spiegel R,Saada A,Flannery PJ,et al.Fatal infantile mitochondrial encephalomyopathy,hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation[J].J Med Genet,2016,53(2):127-131.
[20]Olivotto I,Cecchi F,Poggesi C,et al.Patterns of disease progression in hypertrophic cardiomyopathy:an individualized approach to clinical staging[J].Circ Heart Fail,2012,5(4):535-546.
[21]Watkins H,Ashrafian H,Redwood C.Inherited cardiomyopathies[J].N Engl J Med,2011,364(17):1643-1656.
[22]Wang L,Seidman JG,Seidman CE.Narrative review:harnessing molecular genetics for the diagnosis and management of hypertrophic cardiomyopathy[J].Ann Intern Med,2010,152(8):513-520,W181.
[23]Gersh BJ,Maron BJ,Bonow RO,et al.2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy:executive summary:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines[J].Circulation,2011,124(24):2761-2796.
[24]Piran S,Liu P,Morales A,et al.Where genome meets phenome:rationale for integrating genetic and protein biomarkers in the diagnosis and management of dilated cardiomyopathy and heart failure[J].J Am Coll Cardiol,2012,60(4):283-289.
[25]Olivotto I,Maron MS,Autore C,et al.Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy[J].J Am Coll Cardiol,2008,52(7):559-566.
[26]Turkbey EB,McClelland RL,Kronmal RA,et al.The impact of obesity on the left ventricle:the multi-ethnic study of atherosclerosis(MESA)[J].JACC Cardiovasc Imaging,2010,3(3):266-274.
[27]Abel ED,Litwin SE,Sweeney G.Cardiac remodeling in obesity[J].Physiol Rev,2008,88(2):389-419.
[28]Olivotto I,Maron BJ,Tomberli B,et al.Obesity and its association to phenotype and clinical course in hypertrophic cardiomyopathy[J].J Am Coll Cardiol,2013,62(5):449-457.
[29]Molin DG,Roest PA,Nordstrand H,et al.Disturbed morphogenesis of cardiac outflow tract and increased rate of aortic arch anomalies in the offspring of diabetic rats[J].Birth Defects Res A Clin Mol Teratol,2004,70(12):927-938.
[30]Menezes HS,Barra M,Bello AR,et al.Fetal myocardial hypertrophy in an experimental model of gestational diabetes[J].Cardiol Young,2001,11(6):609-613.
[31]Castellana S,Mastroianno S,Palumbo P,et al.Sudden death in mild hypertrophic cardiomyopathy with compound DSG2/DSC2/MYH6 mutations:Revisiting phenotype after genetic assessment in a master runner athlete[J].J Electrocardiol,2019,53:95-99.
[32]Olmati F,Petramala L,Bisogni V,et al.A rare case report of hypertrophic cardiomyopathy induced by catecholamine-producing tumor[J].Medicine(Baltimore),2018,97(50):e13369.
[33]Nally LM,Conner E,Paige S,et al.Multi-disciplinary evaluation of a 5-month-old with hypertrophic cardiomyopathy related to a functional adrenocortical tumor[J].J Pediatr Endocrinol Metab,2018,31(12):1371-1376.
[34]Adameova A,Abdellatif Y,Dhalla NS.Role of the excessive amounts of circulating catecholamines and glucocorticoids in stress-induced heart disease[J].Can J Physiol Pharmacol,2009,87(7):493-514.
[35]Schwartz BG,Rezkalla S,Kloner RA.Cardiovascular effects of cocaine[J].Circulation,2010,122(24):2558-2569.
[36]Plouin PF,Gimenez-Roqueplo AP.Pheochromocytomas and secreting paragangliomas[J].Orphanet J Rare Dis,2006,1:49.
[37]Kotb MA,Abd ESI,Badr AM,et al.Pulmonary hypertension and cardiac hypertrophy in children recipients of orthotopic living related liver transplantation[J].J Adv Res,2017,8(6):663-668.··352
[2]Rowin EJ,Orfanos A,Estes N,et al.Occurrence and natural history of clinically silent episodes of atrial fibrillation in hypertrophic cardiomyopathy[J].Am J Cardiol,2017,119(11):1862-1865.
[3]Helms AS,Day SM.Hypertrophic cardiomyopathy:single gene disease or complex trait?[J].Eur Heart J,2016,37(23):1823-1825.
[4]Richard P,Charron P,Carrier L,et al.Hypertrophic cardiomyopathy:distribution of disease genes,spectrum of mutations,and implications for a molecular diagnosis strategy[J].Circulation,2003,107(17):2227-2232.
[5]Erdmann J,Daehmlow S,Wischke S,et al.Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy[J].Clin Genet,2003,64(4):339-349.
[6]Millat G,Bouvagnet P,Chevalier P,et al.Prevalence and spectrum of mutations in a cohort of 192 unrelated patients with hypertrophic cardiomyopathy[J].Eur J Med Genet,2010,53(5):261-267.
[7]Kaski JP,Syrris P,Esteban MT,et al.Prevalence of sarcomere protein gene mutations in preadolescent children with hypertrophic cardiomyopathy[J].Circ Cardiovasc Genet,2009,2(5):436-441.
[8]Kimura A,Harada H,Park JE,et al.Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy[J].Nat Genet,1997,16(4):379-382.
[9]Thierfelder L,Watkins H,MacRae C,et al.Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy:a disease of the sarcomere[J].Cell,1994,77(5):701-712.
[10]Farrell E,Armstrong AE,Grimes AC,et al.Transcriptome analysis of cardiac hypertrophic growth in MYBPC3-Null mice suggests early responders in hypertrophic remodeling[J].Front Physiol,2018,9:1442.
[11]Claes GR,van Tienen FH,Lindsey P,et al.Hypertrophic remodelling in cardiac regulatory myosin light chain(MYL2)founder mutation carriers[J].Eur Heart J,2016,37(23):1815-1822.
[12]Mirabel M,Damy T,Donal E,et al.Influence of centre expertise on the diagnosis and management of hypertrophic cardiomyopathy:A study from the French register of hypertrophic cardiomyopathy(REMY)[J].Int J Cardiol,2019,275:107-113.
[13]Ehsan M,Kelly M,Hooper C,et al.Mutant muscle LIM protein C58G causes cardiomyopathy through protein depletion[J].J Mol Cell Cardiol,2018,121:287-296.
[14]Vanninen S,Leivo K,Seppala EH,et al.Heterozygous junctophilin-2(JPH2)p.(Thr161Lys)is a monogenic cause for HCMwith heart failure[J].PLoS One,2018,13(9):e203422.
[15]Walsh R,Buchan R,Wilk A,et al.Defining the genetic architecture of hypertrophic cardiomyopathy:re-evaluating the role of non-sarcomeric genes[J].Eur Heart J,2017,38(46):3461-3468.
[16]Sanderson S,Green A,Preece MA,et al.The incidence of inherited metabolic disorders in the West Midlands,UK[J].Arch Dis Child,2006,91(11):896-899.
[17]Chatterjee A,Seyfferth J,Lucci J,et al.MOF acetyl transferase regulates transcription and respiration in mitochondria[J].Cell,2016,167(3):722-738.
[18]Prendiville TW,Gauvreau K,Tworog-Dube E,et al.Cardiovascular disease in Noonan syndrome[J].Arch Dis Child,2014,99(7):629-634.
[19]Spiegel R,Saada A,Flannery PJ,et al.Fatal infantile mitochondrial encephalomyopathy,hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation[J].J Med Genet,2016,53(2):127-131.
[20]Olivotto I,Cecchi F,Poggesi C,et al.Patterns of disease progression in hypertrophic cardiomyopathy:an individualized approach to clinical staging[J].Circ Heart Fail,2012,5(4):535-546.
[21]Watkins H,Ashrafian H,Redwood C.Inherited cardiomyopathies[J].N Engl J Med,2011,364(17):1643-1656.
[22]Wang L,Seidman JG,Seidman CE.Narrative review:harnessing molecular genetics for the diagnosis and management of hypertrophic cardiomyopathy[J].Ann Intern Med,2010,152(8):513-520,W181.
[23]Gersh BJ,Maron BJ,Bonow RO,et al.2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy:executive summary:a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines[J].Circulation,2011,124(24):2761-2796.
[24]Piran S,Liu P,Morales A,et al.Where genome meets phenome:rationale for integrating genetic and protein biomarkers in the diagnosis and management of dilated cardiomyopathy and heart failure[J].J Am Coll Cardiol,2012,60(4):283-289.
[25]Olivotto I,Maron MS,Autore C,et al.Assessment and significance of left ventricular mass by cardiovascular magnetic resonance in hypertrophic cardiomyopathy[J].J Am Coll Cardiol,2008,52(7):559-566.
[26]Turkbey EB,McClelland RL,Kronmal RA,et al.The impact of obesity on the left ventricle:the multi-ethnic study of atherosclerosis(MESA)[J].JACC Cardiovasc Imaging,2010,3(3):266-274.
[27]Abel ED,Litwin SE,Sweeney G.Cardiac remodeling in obesity[J].Physiol Rev,2008,88(2):389-419.
[28]Olivotto I,Maron BJ,Tomberli B,et al.Obesity and its association to phenotype and clinical course in hypertrophic cardiomyopathy[J].J Am Coll Cardiol,2013,62(5):449-457.
[29]Molin DG,Roest PA,Nordstrand H,et al.Disturbed morphogenesis of cardiac outflow tract and increased rate of aortic arch anomalies in the offspring of diabetic rats[J].Birth Defects Res A Clin Mol Teratol,2004,70(12):927-938.
[30]Menezes HS,Barra M,Bello AR,et al.Fetal myocardial hypertrophy in an experimental model of gestational diabetes[J].Cardiol Young,2001,11(6):609-613.
[31]Castellana S,Mastroianno S,Palumbo P,et al.Sudden death in mild hypertrophic cardiomyopathy with compound DSG2/DSC2/MYH6 mutations:Revisiting phenotype after genetic assessment in a master runner athlete[J].J Electrocardiol,2019,53:95-99.
[32]Olmati F,Petramala L,Bisogni V,et al.A rare case report of hypertrophic cardiomyopathy induced by catecholamine-producing tumor[J].Medicine(Baltimore),2018,97(50):e13369.
[33]Nally LM,Conner E,Paige S,et al.Multi-disciplinary evaluation of a 5-month-old with hypertrophic cardiomyopathy related to a functional adrenocortical tumor[J].J Pediatr Endocrinol Metab,2018,31(12):1371-1376.
[34]Adameova A,Abdellatif Y,Dhalla NS.Role of the excessive amounts of circulating catecholamines and glucocorticoids in stress-induced heart disease[J].Can J Physiol Pharmacol,2009,87(7):493-514.
[35]Schwartz BG,Rezkalla S,Kloner RA.Cardiovascular effects of cocaine[J].Circulation,2010,122(24):2558-2569.
[36]Plouin PF,Gimenez-Roqueplo AP.Pheochromocytomas and secreting paragangliomas[J].Orphanet J Rare Dis,2006,1:49.
[37]Kotb MA,Abd ESI,Badr AM,et al.Pulmonary hypertension and cardiac hypertrophy in children recipients of orthotopic living related liver transplantation[J].J Adv Res,2017,8(6):663-668.··352