{"id":17734,"date":"2017-07-06T14:48:49","date_gmt":"2017-07-06T21:48:49","guid":{"rendered":"https:\/\/mr66givry2.onrocket.site\/?p=17734"},"modified":"2026-01-20T16:20:40","modified_gmt":"2026-01-21T00:20:40","slug":"dm1-genotype-and-cardiac-phenotype","status":"publish","type":"post","link":"https:\/\/myotonic.org\/fr\/dm1-genotype-and-cardiac-phenotype\/","title":{"rendered":"DM1 Genotype and Cardiac Phenotype"},"content":{"rendered":"

DMPK\u00a0<\/em>CTG expansion length generally correlates with the severity of myotonic dystrophy type 1 (DM1), but is not fully prognostic of disease onset, course and severity. For congenital myotonic dystrophy (CDM), the apparent requirement for an epigenetic change upstream of the\u00a0DMPK\u00a0<\/em>locus is apparently a co-requirement, along with a long CTG repeat. Moreover, the relationship between repeat expansion length and the cardiac phenotype in DM is a gap in our understanding of cardiac disease in\u00a0DM1.<\/p>\n

Multivariate Analysis of a Large Genetically Confirmed DM1\u00a0Cohort<\/h2>\n

Dr. Caroline Chong-Nguyen (Sorbonne Paris Cit\u00e9 University) and colleagues characterized the relationship between\u00a0DMPK\u00a0<\/em>repeat expansion length and cardiac disease in a\u00a0retrospective study<\/a>\u00a0of a cohort of 855 adult subjects from the DM1-Heart Registry. Subjects entered into the study had genetic analysis (Southern blot of peripheral blood) done at the time of their baseline cardiac\u00a0investigations.<\/p>\n

Genotyped patients were followed for a median of 11.5 years. The authors utilized a multivariate analysis that considered potential confounding factors, including age, sex, and diabetes\u00a0mellitus.<\/p>\n

Repeat Length is a Key Factor in Prognosis Even When Confounding Variables are Taken into\u00a0Account<\/h2>\n

Survival of DM1 subjects was correlated with the quartile of CTG expansion size\u201437% mortality was reported in subjects with greater than 830 repeats. Across the range of repeat lengths studied, each 500 repeat increase was associated with 1.5-fold higher risk of death from all causes. Heart rate was higher and conduction system disease, left bundle branch block, and longer PR and QRS intervals were more prevalent in subjects with larger repeats. CTG length also associated with the presence of a permanently implanted pacemaker. Availability of extensive longitudinal data allowed the authors to report Kaplan\u2013Meier estimates for survival, supraventricular arrhythmias, pacemaker implantation and sudden\u00a0death.<\/p>\n

This longitudinal study of a large cohort genotyped at the time of initial cardiac evaluation provides new insights into genotype-cardiac phenotype relationships in DM1. Overall, the authors showed that longer\u00a0DMPK\u00a0<\/em>repeat expansions were correlated with the severity of cardiac involvement, including development of conduction defects, left ventricular dysfunction, supraventricular arrhythmias, the requirement for permanent pacing, sudden death and mortality. These findings support a more aggressive approach toward cardiac screening based on\u00a0DMPK\u00a0<\/em>repeat length\u2014the authors argue that care should be based on assessment of conduction system defects and other cardiac\u00a0manifestations.<\/p>\n

This peer-reviewed research article was accompanied by an\u00a0editorial<\/a>\u00a0by Dr. Matthew Wheeler (Stanford University) in the same issue of the journal. This editorial is also referenced\u00a0below.<\/p>\n

References:<\/em><\/p>\n

Association Between Mutation Size and Cardiac Involvement in Myotonic Dystrophy Type 1: An Analysis of the DM1-Heart Registry.<\/a>
\nChong-Nguyen C, Wahbi K, Algalarrondo V, B\u00e9cane HM, Radvanyi-Hoffman H, Arnaud P, Furling D, Lazarus A, Bassez G, B\u00e9hin A, Fayssoil A, Lafor\u00eat P, Stojkovic T, Eymard B, Duboc D.
\nCirc Cardiovasc Genet.<\/strong>\u00a02017 Jun;10(3). pii: e001526. doi: 10.1161\/CIRCGENETICS.116.001526.<\/p>\n

Repeats and Survival in Myotonic Dystrophy Type 1.<\/a>
\nWheeler MT.
\nCirc Cardiovasc Genet.<\/strong>\u00a02017 Jun;10(3). pii: e001783. doi: 10.1161\/CIRCGENETICS.117.001783<\/p>\n","protected":false},"excerpt":{"rendered":"

DMPK\u00a0CTG expansion length generally correlates with the severity of myotonic dystrophy type 1 (DM1), but is not fully prognostic of disease onset, course and severity. For congenital myotonic dystrophy (CDM), the apparent requirement for an epigenetic change upstream of the\u00a0DMPK\u00a0locus is apparently a co-requirement, along with a long CTG repeat. Moreover, the relationship between repeat […]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[72],"tags":[114],"class_list":["post-17734","post","type-post","status-publish","format-standard","hentry","category-research","tag-cardiovascular-system"],"_links":{"self":[{"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/posts\/17734","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/comments?post=17734"}],"version-history":[{"count":0,"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/posts\/17734\/revisions"}],"wp:attachment":[{"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/media?parent=17734"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/categories?post=17734"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/myotonic.org\/fr\/wp-json\/wp\/v2\/tags?post=17734"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}