scholarly journals Case Reports: Emery-Dreifuss Muscular Dystrophy Presenting as a Heart Rhythm Disorders in Children

2021 ◽  
Vol 8 ◽  
Author(s):  
Tatiana Kovalchuk ◽  
Elena Yakovleva ◽  
Svetlana Fetisova ◽  
Tatiana Vershinina ◽  
Viktoriya Lebedeva ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Case Reports ◽  
Sinus Node ◽  
Heart Rhythm ◽  
Cardiac Abnormalities ◽  
Progressive Muscle Weakness ◽  
Cardiac Phenotype ◽  
Cardiac Symptoms ◽  
Heart Rhythm Disorders

Emery-Dreifuss muscular dystrophy (EDMD) is inherited muscle dystrophy often accompanied by cardiac abnormalities in the form of supraventricular arrhythmias, conduction defects and sinus node dysfunction. Cardiac phenotype typically arises years after skeletal muscle presentation, though, could be severe and life-threatening. The defined clinical manifestation with joint contractures, progressive muscle weakness and atrophy, as well as cardiac symptoms are observed by the third decade of life. Still, clinical course and sequence of muscle and cardiac signs may be variable and depends on the genotype. Cardiac abnormalities in patients with EDMD in pediatric age are not commonly seen. Here we describe five patients with different forms of EDMD (X-linked and autosomal-dominant) caused by the mutations in EMD and LMNA genes, presented with early onset of cardiac abnormalities and no prominent skeletal muscle phenotype. The predominant forms of cardiac pathology were atrial arrhythmias and conduction disturbances that progress over time. The presented cases discussed in the light of therapeutic strategy, including radiofrequency ablation and antiarrhythmic devices implantation, and the importance of thorough neurological and genetic screening in pediatric patients presenting with complex heart rhythm disorders.

scholarly journals Emery-Dreifuss muscular dystrophy presenting as a heart rhythm disorders in children

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
T S Kovalchuk ◽  
E V Yakovleva ◽  
S G Fetisova ◽  
T L Vershinina ◽  
T M Pervunina ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Atrial Flutter ◽  
Sinus Node ◽  
Heart Rhythm ◽  
Sinus Node Dysfunction ◽  
Supraventricular Arrhythmias ◽  
Heart Rhythm Disorders ◽  
The Mean

Abstract Introduction Emery-Dreifuss muscular dystrophy (EDMD) is an inherited muscle dystrophy often accompanied by cardiac abnormalities in the form of supraventricular arrhythmias, conduction defects, sinus node dysfunction. Cardiac phenotype typically arises years after skeletal muscle presentations, though, can be severe and life-threatening. The disease usually manifests during the third decade of life with elbow joint contractions and progressive muscle weakness and atrophy. Objective To present our clinical experience of diagnosis and treatment of arrhythmias in children with Emery-Dreifuss muscular dystrophy Materials and methods We enrolled 5 patients with different forms of EDMD (X-linked and autosomal dominant) linked to the mutations in EMD and LMNA genes, presented with early onset of cardiac abnormalities and no leading skeletal muscle phenotype. The predominant forms of cardiac pathology were atrial flutter, atrial fibrillation and conduction disturbances that progress over time. Clinical examination included physical examination, 12-lead electrocardiography, Holter ECG monitoring (HM), transthoracic echocardiography, neurological examination and biochemical and hormone tests. Also we performed CMR, electrophysiological study (EPS), treadmill test of some patients. One patient underwent an endomyocardial biopsy to exclude inflammatory heart disease. Target sequencing was performed using a panel of 108 or 172 genes Results We observed five patients with EDMD and cardiac debut during first-second decades of life: 3 with 1st subtype (variants in EMD gene) and 2 with 2nd subtype (variants in LMNA gene). All patients were males. The mean age of cardiac manifestation was 13,2±3,11 (from 9 to 16 y.o.). The mean follow-up period was 7,4±2,6 years. All patients presented with sinus node dysfunction and four out of five with AV conduction abnormalities. The leading arrhythmic phenotypes included various types of supraventricular arrhythmias: multifocal atrial tachycardia (AT) (n=4), premature atrial captures (PACs) (n=4), atrial flutter, (AF) (n=3), atrial fibrillation (AFib) (n=3) and AV nodal recurrent tachycardia (AVRNT). Heart rhythm disorders were the first manifestation in all three patients with 1st EDMD subtype. Radiofrequency ablation was performed in 2 patients, one of them received permanent pacemaker implantation. Conclusions In conclusion, while being the rare cases, heart rhythm disorders can represent the first and for a long time, the only clinical symptom of EDMD even in the pediatric group of patients. Therefore, thorough laboratory and neurological screening along with genetic studies, are of importance in each pediatric patient presenting with complex heart rhythm disorders of primary supraventricular origin to exclude EDMD or other neuromuscular disorders. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Cardiac Involvement in Facioscapulohumeral Muscular Dystrophy (FSHD)

2021 ◽  
Vol 12 ◽  
Author(s):  
Allison Ducharme-Smith ◽  
Stefan Nicolau ◽  
C. Anwar A. Chahal ◽  
Kirstie Ducharme-Smith ◽  
Shujah Rehman ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Atrioventricular Block ◽  
Cardiac Involvement ◽  
Case Reports ◽  
Shoulder Girdle ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Reduced Ejection Fraction ◽  
Cardiac Abnormalities ◽  
Conduction Abnormality ◽  
Conduction Abnormalities

Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and predominantly affects facial and shoulder girdle muscles. Previous case reports and cohort studies identified minor cardiac abnormalities in FSHD patients, but their nature and frequency remain incompletely characterized.Methods: We reviewed cardiac, neurological and genetic findings of 104 patients with genetically confirmed FSHD.Results: The most common conduction abnormality was complete (7%) or incomplete (5%) right bundle branch block (RBBB). Bifascicular block, left anterior fascicular block, complete atrioventricular block, and 2:1 atrioventricular block each occurred in 1% of patients. Atrial fibrillation or flutter were seen in 5% of patients. Eight percent of patients had heart failure with reduced ejection fraction and 25% had valvular disease. The latter included aortic stenosis in 6% (severe in 4% and moderate in 2%) and moderate aortic regurgitation in 8%. Mitral valve prolapse (MVP) was present in 9% of patients without significant mitral regurgitation. There were no significant associations between structural or conduction abnormalities and age, degree of muscle weakness, or size of the 4q deletion.Conclusions: Both structural and conduction abnormalities can occur in FSHD. The most common abnormalities are benign (RBBB and MVP), but more significant cardiac involvement was also observed. The presence of cardiac abnormalities cannot be predicted from the severity of the neurological phenotype, nor from the genotype.

scholarly journals DUX4 Signalling in the Pathogenesis of Facioscapulohumeral Muscular Dystrophy

2020 ◽  
Vol 21 (3) ◽  
pp. 729 ◽  
Author(s):  
Kenji Rowel Q. Lim ◽  
Quynh Nguyen ◽  
Toshifumi Yokota
Keyword(s):  
Skeletal Muscle ◽  
Cell Death ◽  
Transcription Factor ◽  
Muscular Dystrophy ◽  
Embryonic Development ◽  
Disease Onset ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Signalling Pathways ◽  
Progressive Muscle Weakness ◽  
Homeobox Protein

Facioscapulohumeral muscular dystrophy (FSHD) is a disabling inherited muscular disorder characterized by asymmetric, progressive muscle weakness and degeneration. Patients display widely variable disease onset and severity, and sometimes present with extra-muscular symptoms. There is a consensus that FSHD is caused by the aberrant production of the double homeobox protein 4 (DUX4) transcription factor in skeletal muscle. DUX4 is normally expressed during early embryonic development, and is then effectively silenced in all tissues except the testis and thymus. Its reactivation in skeletal muscle disrupts numerous signalling pathways that mostly converge on cell death. Here, we review studies on DUX4-affected pathways in skeletal muscle and provide insights into how understanding these could help explain the unique pathogenesis of FSHD.

scholarly journals Muscle-Related Plectinopathies

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2480
Author(s):  
Michaela M. Zrelski ◽  
Monika Kustermann ◽  
Lilli Winter
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Epidermolysis Bullosa Simplex ◽  
Progressive Muscle Weakness ◽  
Mitochondrial Alterations ◽  
Cytoplasmic Bodies ◽  
Downstream Effects ◽  
Myasthenic Syndrome ◽  
Genetically Manipulated ◽  
Muscle Biopsies

Plectin is a giant cytoskeletal crosslinker and intermediate filament stabilizing protein. Mutations in the human plectin gene (PLEC) cause several rare diseases that are grouped under the term plectinopathies. The most common disorder is autosomal recessive disease epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), which is characterized by skin blistering and progressive muscle weakness. Besides EBS-MD, PLEC mutations lead to EBS with nail dystrophy, EBS-MD with a myasthenic syndrome, EBS with pyloric atresia, limb-girdle muscular dystrophy type R17, or EBS-Ogna. In this review, we focus on the clinical and pathological manifestations caused by PLEC mutations on skeletal and cardiac muscle. Skeletal muscle biopsies from EBS-MD patients and plectin-deficient mice revealed severe dystrophic features with variation in fiber size, degenerative myofibrillar changes, mitochondrial alterations, and pathological desmin-positive protein aggregates. Ultrastructurally, PLEC mutations lead to a disorganization of myofibrils and sarcomeres, Z- and I-band alterations, autophagic vacuoles and cytoplasmic bodies, and misplaced and degenerating mitochondria. We also summarize a variety of genetically manipulated mouse and cell models, which are either plectin-deficient or that specifically lack a skeletal muscle-expressed plectin isoform. These models are powerful tools to study functional and molecular consequences of PLEC defects and their downstream effects on the skeletal muscle organization.

scholarly journals A Dystrophin Exon-52 Deleted Miniature Pig Model of Duchenne Muscular Dystrophy and Evaluation of Exon Skipping

2021 ◽  
Vol 22 (23) ◽  
pp. 13065
Author(s):  
Yusuke Echigoya ◽  
Nhu Trieu ◽  
William Duddy ◽  
Hong M. Moulton ◽  
HaiFang Yin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Exon Skipping ◽  
Pig Model ◽  
Advanced Technology ◽  
Large Animal ◽  
Miniature Pig ◽  
Cardiac Phenotype ◽  
Dmd Gene

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder caused by mutations in the DMD gene and the subsequent lack of dystrophin protein. Recently, phosphorodiamidate morpholino oligomer (PMO)-antisense oligonucleotides (ASOs) targeting exon 51 or 53 to reestablish the DMD reading frame have received regulatory approval as commercially available drugs. However, their applicability and efficacy remain limited to particular patients. Large animal models and exon skipping evaluation are essential to facilitate ASO development together with a deeper understanding of dystrophinopathies. Using recombinant adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer, we generated a Yucatan miniature pig model of DMD with an exon 52 deletion mutation equivalent to one of the most common mutations seen in patients. Exon 52-deleted mRNA expression and dystrophin deficiency were confirmed in the skeletal and cardiac muscles of DMD pigs. Accordingly, dystrophin-associated proteins failed to be recruited to the sarcolemma. The DMD pigs manifested early disease onset with severe bodywide skeletal muscle degeneration and with poor growth accompanied by a physical abnormality, but with no obvious cardiac phenotype. We also demonstrated that in primary DMD pig skeletal muscle cells, the genetically engineered exon-52 deleted pig DMD gene enables the evaluation of exon 51 or 53 skipping with PMO and its advanced technology, peptide-conjugated PMO. The results show that the DMD pigs developed here can be an appropriate large animal model for evaluating in vivo exon skipping efficacy.

Evaluation and Treatment of Arrhythmias

2012 ◽  
Author(s):  
Peter A. Brady
Keyword(s):  
Ventricular Arrhythmias ◽  
Heart Rate Response ◽  
Sinus Node ◽  
Heart Rhythm ◽  
Holter Monitoring ◽  
Cardiac Conduction ◽  
Electrophysiologic Study ◽  
Heart Rhythm Disorders ◽  
Response To Exercise ◽  
Treadmill Exercise Testing

Abnormal cardiac arrhythmias may be due to reentry, abnormal automaticity, or triggered activity. Reentrant rhythms may be microreentrant or macroreentrant. Ambulatory (Holter) monitoring is useful for the evaluation of both symptomatic and asymptomatic rhythm disturbances and their relationship to daily activity. Treadmill exercise testing is very useful in the evaluation of patients who present with bradycardia and symptoms of palpitations because it allows both documentation of the adequacy of heart rate response to exercise and the recording of the cardiac rhythm during exercise in a controlled setting with ECG monitoring. An electrophysiologic study is useful for assessing sinus node function and the cardiac conduction system and for attempting to induce atrial or ventricular arrhythmias that could explain the clinical presentation. Electrophysiologic study requires placement of electrode catheters in the heart to record and to stimulate heart rhythm. Several therapeutic options are available for heart rhythm disorders, including drug therapy, radiofrequency ablation, and device therapy.

A Famous Chinese Prescription That Promotes Hcn4 Activity in Bone Marrow Mesenchymal Stem Cells is Shenfu Injection: Opinion

2021 ◽  
Vol 7 (4) ◽  
pp. 1-2
Author(s):  
Rong Li ◽  
Keyword(s):  
Sick Sinus Syndrome ◽  
Heart Function ◽  
Sinus Node ◽  
Heart Rhythm ◽  
Underlying Mechanism ◽  
Shenfu Injection ◽  
Chinese Herbal ◽  
Heart Rhythm Disorders ◽  
Marrow Mesenchymal Stem Cells ◽  
Pacemaker Insertion

Sick Sinus Syndrome (SSS) refers to a group of heart rhythm disorders caused by problems relating to the sinus node. Currently, there is no effective treatment for SSS, and an electronic pacemaker is required to support heart function in SSS patients. However, electronic pacemakers are associated with several defects. For example, external magnetic noise commonly interferes, leading to complications. In addition, some patients, especially children with congenitals inoatrial node dysfunction, are not suitable subjects for pacemaker insertion. Therefore, the search for new therapeutic strategies for treating cardiovascular diseases has become imperative. Shenfu injection (SFI), a Chinese herbal medicine, is effective in improving bradyarrhythmia. However, the underlying mechanism of SFI's therapeutic effect remains elusive.

Clinical and Morphological Features of Myocardial Damage and the Course of Fulminant Myocarditis on the Background of СOVID-19, Diagnosis and Treatment Tactics

2020 ◽  
Vol 75 (5S) ◽  
pp. 414-425
Author(s):  
Olga S. Oynotkinova ◽  
Evgenii L. Nikonov ◽  
Oleg V. Zayratyants ◽  
Elena V. Rzhevskaya ◽  
Evgenii V. Krukov ◽  
...  
Keyword(s):  
Myocardial Dysfunction ◽  
Myocardial Damage ◽  
Heart Rhythm ◽  
Microvascular Dysfunction ◽  
Symptomatic Treatment ◽  
Clinical Situation ◽  
Diagnosis And Treatment ◽  
Screening Tests ◽  
Fulminant Myocarditis ◽  
Heart Rhythm Disorders

In a review article based on my own clinical experience of managing patients with acute myocardial injury and fulminant myocarditis, taking into account expert recommendations on the clinical treatment of myocardial damage associated with novel coronavirus infection a National clinical geriatric medical research center, division of cardiovascular diseases, the Chinese geriatrics society, Department of cardiology, Beijing Medical Association and European clinics discusses the pathogenesis, diagnosis and treatment of myocardial damage and FM patients, infected with SARS-CoV-2 in the context of the COVID-19 pandemic. Clinical features and diagnostic criteria are presented, including screening tests of markers of myocardial damage in the form of a highly sensitive troponin test, a natriuretic peptide. The article discusses in detail the pathogenesis and mechanisms of myocardial damage, including immune mechanisms, cytokine storm, systemic inflammation with macro- and microvascular dysfunction and the development of myocardial dysfunction with acute heart failure, hypotension, cardiogenic shock and/or life-threatening heart rhythm disorders caused by hypoxia and metabolic disorders at the cellular level. Features of the clinical course of fulminant myocarditis in infected patients (SARS-CoV-2) in the conditions of the COVID-19 pandemic are presented. For the first time, a detailed histo-morphological analysis of pathological myocardial injuries and complications is presented on the basis of unique autopsy material on post-mortem diagnostics of various pathoanatomic autopsies of those who died from COVID-19 in Moscow. Based on the clinical, functional and morphological material, the Protocol of etiopathogenetic treatment is presented. The basis of standard therapy is considered antiviral drugs, immunoglobulin G, the use of monoclonal antibodies to interleukin-6, anticoagulants, glucocorticoids, depending on the clinical situation, cardioprotectors and symptomatic treatment are recommended to maintain the heart, which in combination can achieve a certain clinical effectiveness. As adjuvant cardioprotective targeted therapy, the sodium salt of phosphocreatine is considered in order to preserve the myocardium, maintain its contractility and vital activity.

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