Abstract Objective To investigate the clinical phenotype and genotype characteristics of children with cardiomyopathy (CM) associated with MYH7 gene mutation. Methods A retrospective analysis was conducted on the medical data of five children with CM caused by MYH7 gene mutation who were diagnosed and treated in the Department of Cardiology, Hebei Children's Hospital. Results Among the five children with CM, there were three girls and two boys, all of whom carried MYH7 gene mutation. Seven mutation sites were identified, among which five were not reported before. Among the five children, there were three children with hypertrophic cardiomyopathy, one child with dilated cardiomyopathy, and one child with noncompaction cardiomyopathy. The age ranged from 6 to 156 months at the initial diagnosis. At the initial diagnosis, two children had the manifestations of heart failure such as cough, shortness of breath, poor feeding, and cyanosis of lips, as well as delayed development; one child had palpitation, blackness, and syncope; one child had fever, runny nose, and abnormal liver function; all five children had a reduction in activity endurance. All five children received pharmacotherapy for improving cardiac function and survived after follow-up for 7-24 months. Conclusions The age of onset varies in children with CM caused by MYH7 gene mutation, and most children lack specific clinical manifestations at the initial diagnosis and may have the phenotype of hypertrophic cardiomyopathy, dilated cardiomyopathy or noncompaction cardiomyopathy. The children receiving early genetic diagnosis and pharmacological intervention result in a favorable short-term prognosis.
LIU Lu,ZHENG Kui,ZHANG Ying-Qian. Phenotype and genotype characteristics of children with cardiomyopathy associated with MYH7 gene mutation: a retrospective analysis[J]. CJCP, 2023, 25(11): 1156-1160.
LIU Lu,ZHENG Kui,ZHANG Ying-Qian. Phenotype and genotype characteristics of children with cardiomyopathy associated with MYH7 gene mutation: a retrospective analysis[J]. CJCP, 2023, 25(11): 1156-1160.
De Angelis G, Bobbo M, Paldino A, et al. Cardiomyopathies in children: classification, diagnosis and treatment[J]. Curr Opin Organ Transplant, 2020, 25(3): 218-230. PMID: 32374574. DOI: 10.1097/MOT.0000000000000755.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. PMID: 25741868. PMCID: PMC4544753. DOI: 10.1038/gim.2015.30.
Kantor PF, Lougheed J, Dancea A, et al. Presentation, diagnosis, and medical management of heart failure in children: Canadian Cardiovascular Society guidelines[J]. Can J Cardiol. 2013;29(12):1535-1552. PMID: 24267800. DOI:10.1016/j.cjca.2013.08.008.
Atemin S, Todorov T, Maver A, et al. MYH7-related disorders in two Bulgarian families: novel variants in the same region associated with different clinical manifestation and disease penetrance[J]. Neuromuscul Disord, 2021, 31(7): 633-641. PMID: 34053846. DOI: 10.1016/j.nmd.2021.04.004.
Hershkovitz T, Kurolap A, Ruhrman-Shahar N, et al. Clinical diversity of MYH7-related cardiomyopathies: insights into genotype-phenotype correlations[J]. Am J Med Genet A, 2019, 179(3): 365-372. PMID: 30588760. DOI: 10.1002/ajmg.a.61017.
Fadl S, W?hlander H, Fall K, et al. The highest mortality rates in childhood dilated cardiomyopathy occur during the first year after diagnosis[J]. Acta Paediatr, 2018, 107(4): 672-677. PMID: 29224255. PMCID: PMC5887975. DOI: 10.1111/apa.14183.
Masarone D, Kaski JP, Pacileo G, et al. Epidemiology and clinical aspects of genetic cardiomyopathies[J]. Heart Fail Clin, 2018, 14(2): 119-128. PMID: 29525641. DOI: 10.1016/j.hfc.2017.12.007.
17 Gao Y, Peng L, Zhao C. MYH7 in cardiomyopathy and skeletal muscle myopathy[J]. Mol Cell Biochem, 2023. Epub ahead of print. PMID: 37079208. DOI: 10.1007/s11010-023-04735-x.
Tajsharghi H, Fyhr IM. Structural effects of the slow/b-cardiac myosin heavy chain R453C mutation in cardiac and skeletal muscle[J]. Scand Cardiovasc J, 2008, 42(2): 153-156. PMID: 18365899. DOI: 10.1080/14017430701762701.
Marschall C, Moscu-Gregor A, Klein HG. Variant panorama in 1,385 index patients and sensitivity of expanded next-generation sequencing panels in arrhythmogenic disorders[J]. Cardiovasc Diagn Ther, 2019, 9(Suppl 2): S292-S298. PMID: 31737537. PMCID: PMC6837920. DOI: 10.21037/cdt.2019.06.06.
Meredith C, Herrmann R, Parry C, et al. Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1)[J]. Am J Hum Genet, 2004, 75(4): 703-708. PMID: 15322983. PMCID: PMC1182058. DOI: 10.1086/424760.
Hirono K, Hata Y, Miyao N, et al. Increased burden of ion channel gene variants is related to distinct phenotypes in pediatric patients with left ventricular noncompaction[J]. Circ Genom Precis Med, 2020, 13(4): e002940. PMID: 32600061. DOI: 10.1161/CIRCGEN.119.002940.
Vershinina T, Fomicheva Y, Muravyev A, et al. Genetic spectrum of left ventricular non-compaction in paediatric patients[J]. Cardiology, 2020, 145(11): 746-756. PMID: 33049752. DOI: 10.1159/000510439.
Mazzarotto F, Hawley MH, Beltrami M, et al. Systematic large-scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies[J]. Genet Med, 2021, 23(5): 856-864. PMID: 33500567. PMCID: PMC8105165. DOI: 10.1038/s41436-020-01049-x.
Franaszczyk M, Truszkowska G, Chmielewski P, et al. Analysis of de novo mutations in sporadic cardiomyopathies emphasizes their clinical relevance and points to novel candidate genes[J]. J Clin Med, 2020, 9(2): 370. PMID: 32013205. PMCID: PMC7073782. DOI: 10.3390/jcm9020370.
de Frutos F, Ochoa JP, Navarro-Pe?alver M, et al. Natural history of MYH7-related dilated cardiomyopathy[J]. J Am Coll Cardiol, 2022, 80(15): 1447-1461. PMID: 36007715. DOI: 10.1016/j.jacc.2022.07.023.
