Cardiac involvement in hereditary myopathy with early respiratory failure: A cohort study

Neurology. 2016 Sep 6;87(10):1031-5. doi: 10.1212/WNL.0000000000003064. Epub 2016 Aug 10.

Abstract

Objective: To assess whether hereditary myopathy with early respiratory failure (HMERF) due to the c.951434T>C; (p.Cys31712Arg) TTN missense mutation also includes a cardiac phenotype.

Method: Clinical cohort study of our HMERF cohort using ECG, 2D echocardiogram, and cross-sectional cardiac imaging with MRI or CT.

Results: We studied 22 participants with the c.951434T>C; (p.Cys31712Arg) TTN missense mutation. Three were deceased. Cardiac conduction abnormalities were identified in 7/22 (32%): sustained atrioventricular tachycardia (n = 2), atrial fibrillation (n = 2), nonsustained atrial tachycardia (n = 1), premature supraventricular complexes (n = 1), and unexplained sinus bradycardia (n = 1). In addition, 4/22 (18%) had imaging evidence of otherwise unexplained cardiomyopathy. These findings are supported by histopathologic correlation suggestive of myocardial cytoskeletal remodeling.

Conclusions: Coexisting cardiac and skeletal muscle involvement is not uncommon in patients with HMERF arising due to the c.951434T>C; (p.Cys31712Arg) TTN mutation. All patients with pathogenic or putative pathogenic TTN mutations should be offered periodic cardiac surveillance.

Publication types

  • Clinical Study

MeSH terms

  • Adolescent
  • Adult
  • Arrhythmias, Cardiac / diagnostic imaging
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / genetics
  • Arrhythmias, Cardiac / physiopathology
  • Blotting, Western
  • Cohort Studies
  • Connectin / genetics
  • Electrocardiography
  • Female
  • Genetic Diseases, Inborn / diagnostic imaging*
  • Genetic Diseases, Inborn / drug therapy
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / physiopathology*
  • Heart / diagnostic imaging*
  • Heart / physiopathology*
  • Humans
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Muscular Diseases / diagnostic imaging*
  • Muscular Diseases / drug therapy
  • Muscular Diseases / genetics
  • Muscular Diseases / physiopathology*
  • Mutation, Missense
  • Myocardium / pathology
  • Phenotype
  • Respiratory Insufficiency / diagnostic imaging*
  • Respiratory Insufficiency / drug therapy
  • Respiratory Insufficiency / genetics
  • Respiratory Insufficiency / physiopathology*
  • Tomography, X-Ray Computed
  • Young Adult

Substances

  • Connectin
  • TTN protein, human

Supplementary concepts

  • Hereditary Myopathy with Early Respiratory Failure