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Current Cardiology Reviews

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ISSN (Print): 1573-403X
ISSN (Online): 1875-6557

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Heart Disease in Mothers of Children with Duchenne Muscular Dystrophy

In Press, (this is not the final "Version of Record"). Available online 23 July, 2024
Author(s): Rose Mary Ferreira Lisboa da Silva*
Published on: 23 July, 2024

Article ID: e230724232195

DOI: 10.2174/011573403X292850240719074112

Price: $95

Abstract

Female carriers of Duchenne Muscular Dystrophy (DMD) carry a heterozygous pathogenic variant in the dystrophin gene and can transmit pathogenic variants to their offspring. DMD is an X-linked recessive disease that affects up to 19.8 in every 100,000 male births. Those carriers with symptoms can be referred to as women with dystrophinopathy. Even among asymptomatic carriers, cardiac involvement can be verified in between 2.5% and 75% through echocardiography. The most commonly affected wall of the left ventricle is the inferolateral, with myocardial fibrosis detected by cardiac nuclear resonance. Therefore, screening is recommended for these women carriers due to the risk of cardiomyopathy. There is a lack of longitudinal studies on the evolution of these carriers. In this article, data on clinical presentation, cardiac assessment for female patients with dystrophinopathy and DMD carriers, and approaches for these patients are discussed.

[1]
Mercuri E, Bönnemann CG, Muntoni F. Muscular dystrophies. Lancet 2019; 394(10213): 2025-38.
[http://dx.doi.org/10.1016/S0140-6736(19)32910-1] [PMID: 31789220]
[2]
Duan D, Goemans N, Takeda S, Mercuri E, Aartsma-Rus A. Duchenne muscular dystrophy. Nat Rev Dis Primers 2021; 7(1): 13.
[http://dx.doi.org/10.1038/s41572-021-00248-3] [PMID: 33602943]
[3]
Crisafulli S, Sultana J, Fontana A, Salvo F, Messina S, Trifirò G. Global epidemiology of Duchenne muscular dystrophy: An updated systematic review and meta-analysis. Orphanet J Rare Dis 2020; 15(1): 141.
[http://dx.doi.org/10.1186/s13023-020-01430-8] [PMID: 32503598]
[4]
Salari N, Fatahi B, Valipour E, et al. Global prevalence of Duchenne and Becker muscular dystrophy: A systematic review and meta-analysis. J Orthop Surg Res 2022; 17(1): 96.
[http://dx.doi.org/10.1186/s13018-022-02996-8] [PMID: 35168641]
[5]
Emery AEH. Duchenne muscular dystrophy—Meryon’s disease. Neuromuscul Disord 1993; 3(4): 263-6.
[http://dx.doi.org/10.1016/0960-8966(93)90018-F] [PMID: 8268722]
[6]
Tyler KL. Origins and early descriptions of “Duchenne muscular dystrophy”. Muscle Nerve 2003; 28(4): 402-22.
[http://dx.doi.org/10.1002/mus.10435] [PMID: 14506712]
[7]
Angelini C. Muscular dystrophy Handbook of Clinical Neurology. 2009.
[http://dx.doi.org/10.1016/S0072-9752(08)02131-3] [PMID: 19892134]
[8]
Kamdar F, Garry DJ. Dystrophin-Deficient Cardiomyopathy. J Am Coll Cardiol 2016; 67(21): 2533-46.
[http://dx.doi.org/10.1016/j.jacc.2016.02.081] [PMID: 27230049]
[9]
Darras BT, Urion DK, Ghosh PS. DystrophinopathiesGeneReviews® Seattle, WA. University of Washington Seattle 2000; pp. 1993-2024.
[10]
Nguyen K, Putoux A, Busa T, et al. Incidental findings on array comparative genomic hybridization: Detection of carrier females of dystrophinopathy without any family history. Clin Genet 2015; 87(5): 488-91.
[http://dx.doi.org/10.1111/cge.12421] [PMID: 24835530]
[11]
Fratter C, Dalgleish R, Allen SK, et al. EMQN best practice guidelines for genetic testing in dystrophinopathies. Eur J Hum Genet 2020; 28(9): 1141-59.
[http://dx.doi.org/10.1038/s41431-020-0643-7] [PMID: 32424326]
[12]
Sarkozy A, Quinlivan R, Bourke JP, et al. 263rd ENMC International Workshop: Focus on female carriers of dystrophinopathy: Refining recommendations for prevention, diagnosis, surveillance, and treatment. Hoofddorp, The Netherlands, 13-15 May 2022. Neuromuscul Disord 2023; 33(3): 274-84.
[http://dx.doi.org/10.1016/j.nmd.2023.01.003] [PMID: 36804616]
[13]
Johansen Taber K, Ben-Shachar R, Torres R, et al. A guidelines-consistent carrier screening panel that supports equity across diverse populations. Genet Med 2022; 24(1): 201-13.
[http://dx.doi.org/10.1016/j.gim.2021.09.009] [PMID: 34906503]
[14]
Singer A, Aartsma-Rus A, Grinshpun-Cohen J, Sagi-Dain L. Lessons learned from the first national population-based genetic carrier-screening program for Duchenne muscular dystrophy. Genet Med 2023; 25(12): 100981.
[http://dx.doi.org/10.1016/j.gim.2023.100981] [PMID: 37712502]
[15]
Cohen G, Shtorch-Asor A, Ben-Shachar S, et al. Large scale population screening for Duchenne muscular dystrophy—Predictable and unpredictable challenges. Prenat Diagn 2022; 42(9): 1162-72.
[http://dx.doi.org/10.1002/pd.6201] [PMID: 35751502]
[16]
Juan-Mateu J, Rodríguez MJ, Nascimento A, et al. Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy. Orphanet J Rare Dis 2012; 7(1): 82.
[http://dx.doi.org/10.1186/1750-1172-7-82] [PMID: 23092449]
[17]
Viggiano E, Picillo E, Cirillo A, Politano L. Comparison of X‐chromosome inactivation in Duchenne muscle/myocardium‐manifesting carriers, non‐manifesting carriers and related daughters. Clin Genet 2013; 84(3): 265-70.
[http://dx.doi.org/10.1111/cge.12048] [PMID: 23110537]
[18]
Ishizaki M, Kobayashi M, Adachi K, Matsumura T, Kimura E. Female dystrophinopathy: Review of current literature. Neuromuscul Disord 2018; 28(7): 572-81.
[http://dx.doi.org/10.1016/j.nmd.2018.04.005] [PMID: 29801751]
[19]
Politano L, Nigro V, Nigro G, et al. Development of cardiomyopathy in female carriers of Duchenne and Becker muscular dystrophies. JAMA 1996; 275(17): 1335-8.
[http://dx.doi.org/10.1001/jama.1996.03530410049032] [PMID: 8614119]
[20]
Solheim TÅ, Fornander F, Raja AA, et al. Cardiac involvement in women with pathogenic dystrophin gene variants. Front Neurol 2021; 12: 707838.
[http://dx.doi.org/10.3389/fneur.2021.707838] [PMID: 34385974]
[21]
Ueda Y, Kawai H, Adachi K, Naruo T, Saito S. [Cardiac dysfunction in female gene carriers of Duchenne muscular dystrophy]. Rinsho Shinkeigaku 1995; 35(11): 1191-8.
[PMID: 8720327]
[22]
Fornander F, Solheim TÅ, Eisum ASV, et al. Quantitative muscle MRI and clinical findings in women with pathogenic dystrophin gene variants. Front Neurol 2021; 12: 707837.
[http://dx.doi.org/10.3389/fneur.2021.707837] [PMID: 34539555]
[23]
Lee SH, Lee JH, Lee KA, Choi YC. Clinical and genetic characterization of female dystrophinopathy. J Clin Neurol 2015; 11(3): 248-51.
[http://dx.doi.org/10.3988/jcn.2015.11.3.248] [PMID: 26022459]
[24]
Giliberto F, Radic CP, Luce L, Ferreiro V, de Brasi C, Szijan I. Symptomatic female carriers of Duchenne muscular dystrophy (DMD): Genetic and clinical characterization. J Neurol Sci 2014; 336(1-2): 36-41.
[http://dx.doi.org/10.1016/j.jns.2013.09.036] [PMID: 24135430]
[25]
Liu C, Ma J, Lu Y, et al. Clinical, pathological, and genetic characterization in a large Chinese cohort with female dystrophinopathy. Neuromuscul Disord 2023; 33(10): 728-36.
[http://dx.doi.org/10.1016/j.nmd.2023.08.008] [PMID: 37716855]
[26]
Adachi K, Kawai H, Saito M, et al. Plasma levels of brain natriuretic peptide as an index for evaluation of cardiac function in female gene carriers of Duchenne muscular dystrophy. Intern Med 1997; 36(7): 497-500.
[http://dx.doi.org/10.2169/internalmedicine.36.497] [PMID: 9240500]
[27]
Hoogerwaard EM, van der Wouw PA, Wilde AAM, et al. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy. Neuromuscul Disord 1999; 9(5): 347-51.
[http://dx.doi.org/10.1016/S0960-8966(99)00018-8] [PMID: 10407858]
[28]
Iwase T, Takao S, Akaike M, et al. Diagnostic utility of cardiac magnetic resonance for detection of cardiac involvement in female carriers of Duchenne muscular dystrophy. Heart Asia 2010; 2(1): 52-5.
[http://dx.doi.org/10.1136/ha.2010.002006] [PMID: 27325943]
[29]
Hoogerwaard EM, Bakker E, Ippel PF, et al. Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the Netherlands: A cohort study. Lancet 1999; 353(9170): 2116-9.
[http://dx.doi.org/10.1016/S0140-6736(98)10028-4] [PMID: 10382696]
[30]
Melacini P, Fanin M, Angelini A, et al. Cardiac transplantation in a Duchenne muscular dystrophy carrier. Neuromuscul Disord 1998; 8(8): 585-90.
[http://dx.doi.org/10.1016/S0960-8966(98)00071-6] [PMID: 10093066]
[31]
Davies JE, Winokur TS, Aaron MF, Benza RL, Foley BA, Holman WL. Cardiomyopathy in a carrier of duchenne’s muscular dystrophy. J Heart Lung Transplant 2001; 20(7): 781-4.
[http://dx.doi.org/10.1016/S1053-2498(00)00240-0] [PMID: 11448811]
[32]
Cullom C, Vo V, McCabe MD. Orthotopic heart transplantation in manifesting carrier of duchenne muscular dystrophy. J Cardiothorac Vasc Anesth 2022; 36(8) (8 Pt A): 2593-9.
[http://dx.doi.org/10.1053/j.jvca.2021.09.047] [PMID: 34670720]
[33]
Feingold B, Mahle WT, Auerbach S, et al. Management of cardiac involvement associated with neuromuscular diseases: A scientific statement from the american heart association. Circulation 2017; 136(13): e200-31.
[http://dx.doi.org/10.1161/CIR.0000000000000526] [PMID: 28838934]
[34]
Bogue L, Peay H, Martin A, Lucas A, Ramchandren S. Knowledge of carrier status and barriers to testing among mothers of sons with Duchenne or Becker muscular dystrophy. Neuromuscul Disord 2016; 26(12): 860-4.
[http://dx.doi.org/10.1016/j.nmd.2016.09.008] [PMID: 27863875]
[35]
Eekhoff L, Edwards J, Martin A, Prijoles EJ. Assessing the barriers to cardiac care in carriers of Duchenne and Becker muscular dystrophy. J Genet Couns 2019; 28(5): 993-1002.
[http://dx.doi.org/10.1002/jgc4.1151] [PMID: 31373078]
[36]
Hoefel AML, Weschenfelder CA, Rosa BF, Donis KC, Saute JAM. Empowerment of genetic information by women at-risk of being carriers of Duchenne and Becker muscular dystrophies. J Community Genet 2024; 15(2): 163-75.
[http://dx.doi.org/10.1007/s12687-023-00695-3] [PMID: 38165635]
[37]
Lim KRQ, Sheri N, Nguyen Q, Yokota T. Cardiac involvement in dystrophin-deficient females: Current understanding and implications for the treatment of dystrophinopathies. Genes (Basel) 2020; 11(7): 765.
[http://dx.doi.org/10.3390/genes11070765] [PMID: 32650403]
[38]
Thomas GD. Functional muscle ischemia in Duchenne and Becker muscular dystrophy. Front Physiol 2013; 4: 381.
[http://dx.doi.org/10.3389/fphys.2013.00381] [PMID: 24391598]
[39]
Dombernowsky NW, Ölmestig JNE, Witting N, Kruuse C. Role of neuronal nitric oxide synthase (nNOS) in Duchenne and Becker muscular dystrophies – Still a possible treatment modality? Neuromuscul Disord 2018; 28(11): 914-26.
[http://dx.doi.org/10.1016/j.nmd.2018.09.001] [PMID: 30352768]
[40]
Grain L, Cortina-Borja M, Forfar C, Hilton-Jones D, Hopkin J, Burch M. Cardiac abnormalities and skeletal muscle weakness in carriers of Duchenne and Becker muscular dystrophies and controls. Neuromuscul Disord 2001; 11(2): 186-91.
[http://dx.doi.org/10.1016/S0960-8966(00)00185-1] [PMID: 11257476]
[41]
Mccaffrey T, Guglieri M, Murphy AP, Bushby K, Johnson A, Bourke JP. Cardiac involvement in female carriers of duchenne or becker muscular dystrophy. Muscle Nerve 2017; 55(6): 810-8.
[http://dx.doi.org/10.1002/mus.25445] [PMID: 27761893]
[42]
Kincl V, Panovský R, Pešl M, et al. Echocardiographic signs of subclinical cardiac function impairment in Duchenne dystrophy gene carriers. Sci Rep 2020; 10(1): 20794.
[http://dx.doi.org/10.1038/s41598-020-77882-6] [PMID: 33247228]
[43]
Adachi K, Hashiguchi S, Saito M, et al. Detection and management of cardiomyopathy in female dystrophinopathy carriers. J Neurol Sci 2018; 386: 74-80.
[http://dx.doi.org/10.1016/j.jns.2017.12.024] [PMID: 29358000]
[44]
van Westrum SMS, Hoogerwaard EM, Dekker L, et al. Cardiac abnormalities in a follow-up study on carriers of Duchenne and Becker muscular dystrophy. Neurology 2011; 77(1): 62-6.
[http://dx.doi.org/10.1212/WNL.0b013e318221ad14] [PMID: 21700587]
[45]
Liu C, Ferrari VA, Han Y. Cardiovascular magnetic resonance imaging and heart failure. Curr Cardiol Rep 2021; 23(4): 35.
[http://dx.doi.org/10.1007/s11886-021-01464-9] [PMID: 33686516]
[46]
Florian A, Rösch S, Bietenbeck M, et al. Cardiac involvement in female Duchenne and Becker muscular dystrophy carriers in comparison to their first-degree male relatives: A comparative cardiovascular magnetic resonance study. Eur Heart J Cardiovasc Imaging 2016; 17(3): 326-33.
[http://dx.doi.org/10.1093/ehjci/jev161] [PMID: 26113120]
[47]
Wexberg P, Avanzini M, Mascherbauer J, et al. Myocardial late gadolinium enhancement is associated with clinical presentation in Duchenne muscular dystrophy carriers. J Cardiovasc Magn Reson 2016; 18(1): 61.
[http://dx.doi.org/10.1186/s12968-016-0281-y] [PMID: 27660108]
[48]
Masárová L, Panovský R, Pešl M, et al. Myocardial native T1 mapping and extracellular volume quantification in asymptomatic female carriers of Duchenne muscular dystrophy gene mutations. Orphanet J Rare Dis 2023; 18(1): 283.
[http://dx.doi.org/10.1186/s13023-023-02899-9] [PMID: 37697356]
[49]
Tang L, Shao S, Wang C. Electrocardiographic features of children with Duchenne muscular dystrophy. Orphanet J Rare Dis 2022; 17(1): 320.
[http://dx.doi.org/10.1186/s13023-022-02473-9] [PMID: 35987773]
[50]
Mah ML, Cripe L, Slawinski MK, et al. Duchenne and Becker muscular dystrophy carriers: Evidence of cardiomyopathy by exercise and cardiac MRI testing. Int J Cardiol 2020; 316: 257-65.
[http://dx.doi.org/10.1016/j.ijcard.2020.05.052] [PMID: 32473283]
[51]
Azzu A, Antonopoulos AS, Krupickova S, et al. Myocardial strain analysis by cardiac magnetic resonance 3D feature-tracking identifies subclinical abnormalities in patients with neuromuscular disease and no overt cardiac involvement. Eur Heart J Cardiovasc Imaging 2023; 24(4): 503-11.
[http://dx.doi.org/10.1093/ehjci/jeac129] [PMID: 35793360]
[52]
Kondo T, Okumura T, Takefuji M, et al. Long-term pathological follow-up of myocardium in a carrier of duchenne muscular dystrophy with dilated cardiomyopathy. Circ Heart Fail 2017; 10(3): e003826.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.003826] [PMID: 28235759]
[53]
Mavrogeni S, Bratis K, Papavasiliou A, et al. CMR detects subclinical cardiomyopathy in mother-carriers of Duchenne and Becker muscular dystrophy. JACC Cardiovasc Imaging 2013; 6(4): 526-8.
[http://dx.doi.org/10.1016/j.jcmg.2012.09.017] [PMID: 23579015]
[54]
Giglio V, Puddu PE, Camastra G, et al. Patterns of late gadolinium enhancement in Duchenne muscular dystrophy carriers. J Cardiovasc Magn Reson 2014; 16(1): 45.
[http://dx.doi.org/10.1186/1532-429X-16-45] [PMID: 25008475]
[55]
Schelhorn J, Schoenecker A, Neudorf U, et al. Cardiac pathologies in female carriers of Duchenne muscular dystrophy assessed by cardiovascular magnetic resonance imaging. Eur Radiol 2015; 25(10): 3066-72.
[http://dx.doi.org/10.1007/s00330-015-3694-3] [PMID: 25791640]
[56]
Lang SM, Shugh S, Mazur W, et al. Myocardial Fibrosis and left ventricular dysfunction in duchenne muscular dystrophy carriers using cardiac magnetic resonance imaging. Pediatr Cardiol 2015; 36(7): 1495-501.
[http://dx.doi.org/10.1007/s00246-015-1192-7] [PMID: 25976773]
[57]
Han S, Xu H, Zheng J, et al. Population-wide duchenne muscular dystrophy carrier detection by CK and molecular testing. BioMed Res Int 2020; 2020: 1-12.
[http://dx.doi.org/10.1155/2020/8396429] [PMID: 33029525]
[58]
Fortunato F, Ferlini A. Biomarkers in Duchenne Muscular Dystrophy: Current status and future directions. J Neuromuscul Dis 2023; 10(6): 987-1002.
[http://dx.doi.org/10.3233/JND-221666] [PMID: 37545256]
[59]
Armstrong N, Apkon S, Berggren KN, et al. The early care (0–3 years) in duchenne muscular dystrophy meeting report. J Neuromuscul Dis 2024; 11(2): 1-9.
[http://dx.doi.org/10.3233/JND-230180] [PMID: 38189762]
[60]
Spurney CF, Ascheim D, Charnas L, et al. Current state of cardiac troponin testing in Duchenne muscular dystrophy cardiomyopathy: Review and recommendations from the Parent Project Muscular Dystrophy expert panel. Open Heart 2021; 8(1): e001592.
[http://dx.doi.org/10.1136/openhrt-2021-001592] [PMID: 33762424]
[61]
Florian A, Patrascu A, Tremmel R, et al. Identification of Cardiomyopathy-Associated Circulating miRNA Biomarkers in muscular dystrophy female carriers using a complementary cardiac imaging and plasma profiling approach. Front Physiol 2018; 9: 1770.
[http://dx.doi.org/10.3389/fphys.2018.01770] [PMID: 30622476]
[62]
Mousa NO, Abdellatif A, Fahmy N, Zada S, El-Fawal H, Osman A. Circulating MicroRNAs in Duchenne Muscular Dystrophy. Clin Neurol Neurosurg 2020; 189: 105634.
[http://dx.doi.org/10.1016/j.clineuro.2019.105634] [PMID: 31838454]
[63]
Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022; 145(18): e895-e1032.
[http://dx.doi.org/10.1161/CIR.0000000000001063] [PMID: 35363499]
[64]
McDonagh TA, Metra M, Adamo M, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail 2024; 26(1): 5-17.
[http://dx.doi.org/10.1002/ejhf.3024] [PMID: 38169072]
[65]
Finsterer J, Stöllberger C, Freudenthaler B, De Simoni D, Höftberger R, Wagner K. Muscular and cardiac manifestations in a Duchenne-carrier harboring a <i>dystrophin</i> deletion of exons 12-29. Intractable Rare Dis Res 2018; 7(2): 120-5.
[http://dx.doi.org/10.5582/irdr.2018.01003] [PMID: 29862154]
[66]
Earl CC, Soslow JH, Markham LW, Goergen CJ. Myocardial strain imaging in Duchenne muscular dystrophy. Front Cardiovasc Med 2022; 9: 1031205.
[http://dx.doi.org/10.3389/fcvm.2022.1031205] [PMID: 36505382]

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