Dilated, Arrhythmogenic Cardiomyopathy in Emery-Dreifuss Muscular Dystrophy Due to the Emerin Splice-Site Mutation c.449 + 1G&gt;A

Finsterer, Josef; Stöllberger, Claudia; Sehnal, Ernst; Rehder, Helga; Laccone, Franco

doi:10.1159/000368222

Cited by 12 publications

(8 citation statements)

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“…CI in X-EDMD due to emerin mutations has been occasionally reported and manifests as CCDs. 38) Rarely, dCMP in association with life-threatening ventricular arrhythmias has also been reported. 38) A subset of patients with X-EDMD due to FHL1 mutations can present with pulmonary artery hypoplasia or SCD ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

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Heart Disease in Disorders of Muscle, Neuromuscular Transmission, and the Nerves

Finsterer

Stöllberger

2016

Korean Circ J

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Little is known regarding cardiac involvement (CI) by neuromuscular disorders (NMDs). The purpose of this review is to summarise and discuss the major findings concerning the types, frequency, and severity of cardiac disorders in NMDs as well as their diagnosis, treatment, and overall outcome. CI in NMDs is characterized by pathologic involvement of the myocardium or cardiac conduction system. Less commonly, additional critical anatomic structures, such as the valves, coronary arteries, endocardium, pericardium, and even the aortic root may be involved. Involvement of the myocardium manifests most frequently as hypertrophic or dilated cardiomyopathy and less frequently as restrictive cardiomyopathy, non-compaction, arrhythmogenic right-ventricular dysplasia, or Takotsubo-syndrome. Cardiac conduction defects and supraventricular and ventricular arrhythmias are common cardiac manifestations of NMDs. Arrhythmias may evolve into life-threatening ventricular tachycardias, asystole, or even sudden cardiac death. CI is common and carries great prognostic significance on the outcome of dystrophinopathies, laminopathies, desminopathies, nemaline myopathy, myotonias, metabolic myopathies, Danon disease, and Barth-syndrome. The diagnosis and treatment of CI in NMDs follows established guidelines for the management of cardiac disease, but cardiotoxic medications should be avoided. CI in NMDs is relatively common and requires complete work-up following the establishment of a neurological diagnosis. Appropriate cardiac treatment significantly improves the overall long-term outcome of NMDs.

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Section: Resultsmentioning

confidence: 99%

“… 38) Rarely, dCMP in association with life-threatening ventricular arrhythmias has also been reported. 38) A subset of patients with X-EDMD due to FHL1 mutations can present with pulmonary artery hypoplasia or SCD ( Table 3 ). 39) In another study, FHL1 patients presented with myocardial thickening, hCMP, and SCD.…”

Section: Resultsmentioning

confidence: 99%

Heart Disease in Disorders of Muscle, Neuromuscular Transmission, and the Nerves

Finsterer

Stöllberger

2016

Korean Circ J

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“…Emerin (encoded by EMD) is ubiquitously expressed and located in the inner nuclear membrane13. A mutation in EMD in humans is a cause of Emery-Dreifuss muscular dystrophy (EDMD) and results in a disorder of skeletal muscle and cardiac muscle including a cardiac conduction aberration and dilated cardiomyopathy (DCM)141516. Emerin binds to several nuclear proteins and performs various functions in the nuclear lamina, nuclear structure, transcriptional regulation, and chromatin architecture171819.…”

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Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient

Shimojima

Yuasa

Motoda

et al. 2017

Sci Rep

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Alteration of the nuclear Ca2+ transient is an early event in cardiac remodeling. Regulation of the nuclear Ca2+ transient is partly independent of the cytosolic Ca2+ transient in cardiomyocytes. One nuclear membrane protein, emerin, is encoded by EMD, and an EMD mutation causes Emery-Dreifuss muscular dystrophy (EDMD). It remains unclear whether emerin is involved in nuclear Ca2+ homeostasis. The aim of this study is to elucidate the role of emerin in rat cardiomyocytes by means of hypertrophic stimuli and in EDMD induced pluripotent stem (iPS) cell-derived cardiomyocytes in terms of nuclear structure and the Ca2+ transient. The cardiac hypertrophic stimuli increased the nuclear area, decreased nuclear invagination, and increased the half-decay time of the nuclear Ca2+ transient in cardiomyocytes. Emd knockdown cardiomyocytes showed similar properties after hypertrophic stimuli. The EDMD-iPS cell-derived cardiomyocytes showed increased nuclear area, decreased nuclear invagination, and increased half-decay time of the nuclear Ca2+ transient. An autopsied heart from a patient with EDMD also showed increased nuclear area and decreased nuclear invagination. These data suggest that Emerin plays a crucial role in nuclear structure and in the nuclear Ca2+ transient. Thus, emerin and the nuclear Ca2+ transient are possible therapeutic targets in heart failure and EDMD.

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“…Differences in cardiac presentation, including the severity of LV enlargement and systolic dysfunction, were postulated [7,35]. LMNA is one of the most common DCMcausing genes in patients with no peripheral muscle involvement.…”

Section: Discussionmentioning

confidence: 99%

Echocardiographic Features of Cardiomyopathy in Emery-Dreifuss Muscular Dystrophy

Marchel

Madej-Pilarczyk

Tymińska

et al. 2021

Cardiology Research and Practice

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Background. Emery-Dreifuss muscular dystrophy (EDMD) is a very rare type of muscular dystrophy characterized by musculoskeletal abnormalities accompanied by cardiac defects. Two most common genetic subtypes are EDMD1 due to EMD and EDMD2 caused by LMNA gene mutations. The aim of the study was to characterize and compare the cardiac morphology and function in the two main genetic subgroups of EDMD with the use of echocardiography. Methods. 41 patients with EDMD (29 EDMD1 and 12 EDMD2) as well as 25 healthy controls were enrolled in our study. Transthoracic echo with the use of a prescribed protocol was performed. Results. Highly statistically significant differences with regard to left ventricle (LV) volumes between the EDMD and the control group were found. 51% of EDMD patients had an enlarged left atrium and as many as 71% had an enlarged right atrium. The LV ejection fraction (LVEF) was significantly lower in EDMD patients than in the control group which corresponded also with a lower systolic velocity of the mitral annulus. 43% of EDMD patients had LVEF below the normal limit. Diastolic dysfunction was detected in 17% of EDMD patients. There were no significant differences between the two types of EDMD in terms of diameters and volumes of any chamber, as well as the systolic function of both left and right ventricles. Conclusions. A significant number of EDMD patients present LV dilatation and different degrees of systolic dysfunction. Dilatation of the atria dominates over ventricle dilatation. We did not present any significant differences between EDMD1 and EDMD2 in terms of the morphology and the function of the heart.

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Dilated, Arrhythmogenic Cardiomyopathy in Emery-Dreifuss Muscular Dystrophy Due to the Emerin Splice-Site Mutation c.449 + 1G>A

Cited by 12 publications

References 11 publications

Heart Disease in Disorders of Muscle, Neuromuscular Transmission, and the Nerves

Heart Disease in Disorders of Muscle, Neuromuscular Transmission, and the Nerves

Emerin plays a crucial role in nuclear invagination and in the nuclear calcium transient

Echocardiographic Features of Cardiomyopathy in Emery-Dreifuss Muscular Dystrophy

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