Muscular Dystrophy Research Today is a free monthly online journal that collates and summarizes the latest research about Muscular Dystrophy, including details on duchenne muscular dystrophy, symptoms, treatment.

Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1.

Groh WJ, Groh MR, Saha C, Kincaid JC, Simmons Z, Ciafaloni E, Pourmand R, Otten RF, Bhakta D, Nair GV, Marashdeh MM, Zipes DP, Pascuzzi RM

Department of Medicine, Krannert Institute of Cardiology, Indiana University, Indianapolis 46202, USA. wgroh@iupui.edu

BACKGROUND: Sudden death can occur as a consequence of cardiac-conduction abnormalities in the neuromuscular disease myotonic dystrophy type 1. The determinants of the risk of sudden death remain imprecise. METHODS: We assessed whether the electrocardiogram (ECG) was useful in predicting sudden death in 406 adult patients with genetically confirmed myotonic dystrophy type 1. A patient was characterized as having a severe abnormality if the ECG had at least one of the following features: rhythm other than sinus, PR interval of 240 msec or more, QRS duration of 120 msec or more, or second-degree or third-degree atrioventricular block. RESULTS: Patients with severe abnormalities according to the entry ECG were older than patients without severe abnormalities, had more severe skeletal-muscle impairment, and were more likely to have heart failure, left ventricular systolic dysfunction, or atrial tachyarrhythmia. Such patients were more likely to receive a pacemaker or an implantable cardioverter-defibrillator during the follow-up period. During a mean follow-up period of 5.7 years, 81 patients died; there were 27 sudden deaths, 32 deaths from progressive neuromuscular respiratory failure, 5 nonsudden deaths from cardiac causes, and 17 deaths from other causes. Among the 17 patients who died suddenly in whom postcollapse rhythm was evaluated, a ventricular tachyarrhythmia was observed in 9. A severe ECG abnormality (relative risk, 3.30; 95% confidence interval [CI], 1.24 to 8.78) and a clinical diagnosis of atrial tachyarrhythmia (relative risk, 5.18; 95% CI, 2.28 to 11.77) were independent risk factors for sudden death. CONCLUSIONS: Patients with adult myotonic dystrophy type 1 are at high risk for arrhythmias and sudden death. A severe abnormality on the ECG and a diagnosis of an atrial tachyarrhythmia predict sudden death. (ClinicalTrials.gov number, NCT00622453.)

Published 20 June 2008 in N Engl J Med, 358(25): 2688-97.
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Articles on Muscular Dystrophy published 2 June 2008:

Characteristics and outcomes of cardiomyopathy in children with Duchenne or Becker muscular dystrophy: a comparative study from the Pediatric Cardiomyopathy Registry.   Am Heart J, 155(6): 998-1005.

OBJECTIVE: The aim of this study was to determine in pediatric Duchenne (DMD) and Becker muscular dystrophy (BMD) or other dilated cardiomyopathies (ODCM) whether outcomes differ by diagnosis. BACKGROUND: Children with dilated cardiomyopathy are treated as a single undifferentiated group. METHODS: This cohort study of 128 children with DMD, 15 with BMD, and 312 with ODCM uses outcome measures of left ventricular (LV) size and function, death, heart transplant, and death or transplant. RESULTS: ... [Abstract] [Full-text]

Solution structure of the inner DysF domain of myoferlin and implications for limb girdle muscular dystrophy type 2b.   J Mol Biol, 379(5): 981-90.

Mutations in the protein dysferlin, a member of the ferlin family, lead to limb girdle muscular dystrophy type 2B and Myoshi myopathy. The ferlins are large proteins characterised by multiple C2 domains and a single C-terminal membrane-spanning helix. However, there is sequence conservation in some of the ferlin family in regions outside the C2 domains. In one annotation of the domain structure of these proteins, an unusual internal duplication event has been noted where a putative domain is ... [Abstract] [Full-text]

A novel SNaPshot assay to detect the mdx mutation.   Muscle Nerve, 37(6): 731-5.

The mdx mouse is an animal model for Duchenne muscular dystrophy (DMD). In order to evaluate possible treatments and to carry out genetic studies, it is essential to distinguish between mice that carry the dystrophic (mutant) or wild-type (wt) allele(s). The current amplification-resistant mutation system (ARMS) assay is labor intensive and yields false negatives, which reduces its efficiency as a screening tool. An alternate assay based on single-nucleotide polymorphism (SNP) primer extension ... [Abstract] [Full-text]

Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle.   Hum Mol Genet, 17(12): 1855-66.

Muscular dystrophies comprise a genetically heterogeneous group of degenerative muscle disorders characterized by progressive muscle wasting and weakness. Two forms of limb-girdle muscular dystrophy, 2A and 2B, are caused by mutations in calpain 3 (CAPN3) and dysferlin (DYSF), respectively. While CAPN3 may be involved in sarcomere remodeling, DYSF is proposed to play a role in membrane repair. The coexistence of CAPN3 and AHNAK, a protein involved in subsarcolemmal cytoarchitecture and membrane ... [Abstract] [Full-text]

Articles on Muscular Dystrophy published 30 May 2008:

L-arginine decreases inflammation and modulates the nuclear factor-kappaB/matrix metalloproteinase cascade in mdx muscle fibers.   Am J Pathol, 172(6): 1509-19.

Duchenne muscular dystrophy (DMD) is a lethal, X-linked disorder associated with dystrophin deficiency that results in chronic inflammation, sarcolemma damage, and severe skeletal muscle degeneration. Recently, the use of L-arginine, the substrate of nitric oxide synthase (nNOS), has been proposed as a pharmacological treatment to attenuate the dystrophic pattern of DMD. However, little is known about signaling events that occur in dystrophic muscle with l-arginine treatment. Considering the ... [Abstract] [Full-text]

Articles on Muscular Dystrophy published 29 May 2008:

Log-PCR: a new tool for immediate and cost-effective diagnosis of up to 85% of dystrophin gene mutations.   Clin Chem, 54(6): 973-81.

BACKGROUND: Duchenne (DMD) and Becker (BMD) muscular dystrophies are caused by mutations in the dystrophin gene. Despite the progress in the technologies of mutation detection, the disease of one third of patients escapes molecular definition because the labor and expense involved has precluded analyzing the entire gene. Novel techniques with higher detection rates, such as multiplex ligation-dependent probe amplification and multiplex amplifiable probe hybridization, have been introduced. ... [Abstract] [Full-text]

Articles on Muscular Dystrophy published 20 May 2008:

A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy.   Ann Neurol, 63(5): 561-71.

OBJECTIVE: Myostatin is an endogenous negative regulator of muscle growth and a novel target for muscle diseases. We conducted a safety trial of a neutralizing antibody to myostatin, MYO-029, in adult muscular dystrophies (Becker muscular dystrophy, facioscapulohumeral dystrophy, and limb-girdle muscular dystrophy). METHODS: This double-blind, placebo-controlled, multinational, randomized study included 116 subjects divided into sequential dose-escalation cohorts, each receiving MYO-029 or ... [Abstract] [Full-text]

Articles on Muscular Dystrophy published 19 May 2008:

Oculopharyngeal myopathy with inflammation and calcinosis: an unusual phenotype.   J Neurol Neurosurg Psychiatry, 79(6): 731-3.

The case is reported of a patient with progressive proximal and distal weakness, dysphagia, respiratory weakness, calcifications, ptosis and ophthalmoparesis with inflammation, rimmed vacuoles and positive amyloid and ubiquitin on muscle biopsy. The histopathological features fit best with inclusion body myositis, but ophthalmoparesis and ptosis have not previously been described. The clinical phenotype fits best with hereditary inclusion body myopathy or distal-oculopharyngeal muscular ... [Abstract] [Full-text]

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