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Neurologic Clinics Aug 2014Myotonic dystrophy (dystrophia myotonica, DM) is one of the most common lethal monogenic disorders in populations of European descent. DM type 1 was first described over... (Review)
Review
Myotonic dystrophy (dystrophia myotonica, DM) is one of the most common lethal monogenic disorders in populations of European descent. DM type 1 was first described over a century ago. More recently, a second form of the disease, DM type 2 was recognized, which results from repeat expansion in a different gene. Both disorders have autosomal dominant inheritance and multisystem features, including myotonic myopathy, cataract, and cardiac conduction disease. This article reviews the clinical presentation and pathophysiology of DM and discusses current management and future potential for developing targeted therapies.
Topics: Europe; Female; Humans; Male; Myotonic Dystrophy
PubMed: 25037086
DOI: 10.1016/j.ncl.2014.04.011 -
Continuum (Minneapolis, Minn.) Dec 2022Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are genetic disorders affecting skeletal and smooth muscle, heart, brain, eyes, and other organs. The... (Review)
Review
PURPOSE OF REVIEW
Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are genetic disorders affecting skeletal and smooth muscle, heart, brain, eyes, and other organs. The multisystem involvement and disease variability of myotonic dystrophy have presented challenges for clinical care and research. This article focuses on the diagnosis and management of the disease. In addition, recent advances in characterizing the diverse clinical manifestations and variability of the disease are discussed.
RECENT FINDINGS
Studies of the multisystem involvement of myotonic dystrophy, including the most lethal cardiac and respiratory manifestations and their molecular underpinnings, expand our understanding of the myotonic dystrophy phenotype. Advances have been made in understanding the molecular mechanisms of both types of myotonic dystrophy, providing opportunities for developing targeted therapeutics, some of which have entered clinical trials in DM1.
SUMMARY
Continued efforts focus on advancing our molecular and clinical understanding of DM1 and DM2. Accurately measuring and monitoring the diverse and variable clinical manifestations of myotonic dystrophy in clinic and in research is important to provide adequate care, prevent complications, and find treatments that improve symptoms and life quality.
Topics: Humans; Myotonic Dystrophy; Phenotype; Brain
PubMed: 36537977
DOI: 10.1212/CON.0000000000001184 -
Acta Myologica : Myopathies and... Dec 2020The myotonic dystrophies are the commonest cause of adult-onset muscular dystrophy. Phenotypes of DM1 and DM2 are similar, but there are some important differences,... (Review)
Review
The myotonic dystrophies are the commonest cause of adult-onset muscular dystrophy. Phenotypes of DM1 and DM2 are similar, but there are some important differences, including the presence or absence of congenital form, muscles primarily affected (distal vs proximal), involved muscle fiber types (type 1 vs type 2 fibers), and some associated multisystemic phenotypes. There is currently no cure for the myotonic dystrophies but effective management significantly reduces the morbidity and mortality of patients. For the enormous understanding of the molecular pathogenesis of myotonic dystrophy type 1 and myotonic dystrophy type 2, these diseases are now called "spliceopathies" and are mediated by a primary disorder of RNA rather than proteins. Despite clinical and genetic similarities, myotonic dystrophy type 1 and type 2 are distinct disorders requiring different diagnostic and management strategies. Gene therapy for myotonic dystrophy type 1 and myotonic dystrophy type 2 appears to be very close and the near future is an exciting time for clinicians and patients.
Topics: Humans; Microsatellite Repeats; Myotonic Dystrophy; Myotonin-Protein Kinase; RNA-Binding Proteins
PubMed: 33458578
DOI: 10.36185/2532-1900-026 -
Drug Discovery Today Mar 2023The beginning of the 20th decade has witnessed an increase in drug development programs for myotonic dystrophy type 1 (DM1). We have collected nearly 20 candidate drugs... (Review)
Review
The beginning of the 20th decade has witnessed an increase in drug development programs for myotonic dystrophy type 1 (DM1). We have collected nearly 20 candidate drugs with accomplished preclinical and clinical phases, updating our previous drug development pipeline review with new entries and relevant milestones for pre-existing candidates. Three interventional first-in-human clinical trials got underway with distinct drug classes, namely AOC 1001 and DYNE-101 nucleic acid-based therapies, and the small molecule pitolisant, which joins the race toward market authorization with other repurposed drugs, including tideglusib, metformin, or mexiletine, already in clinical evaluation. Furthermore, newly disclosed promising preclinical data for several additional nucleic-acid therapeutic candidates and a CRISPR-based approach, as well as the advent into the pipeline of novel therapeutic programs, increase the plausibility of success in the demanding task of providing valid treatments to patients with DM1.
Topics: Humans; Myotonic Dystrophy; Drug Development
PubMed: 36634841
DOI: 10.1016/j.drudis.2023.103489 -
Neurologia Apr 2020Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of...
BACKGROUND AND OBJECTIVES
Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1.
MATERIAL AND METHODS
Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide.
RECOMMENDATIONS
The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives.
CONCLUSION
MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.
Topics: Deglutition Disorders; Follow-Up Studies; Genetic Counseling; Humans; Myotonic Dystrophy; Practice Guidelines as Topic
PubMed: 31003788
DOI: 10.1016/j.nrl.2019.01.001 -
Semergen Oct 2020
Topics: Follow-Up Studies; Humans; Myotonic Dystrophy; Plant Extracts; Primary Health Care
PubMed: 33039262
DOI: 10.1016/j.semerg.2020.09.001 -
Continuum (Minneapolis, Minn.) Dec 2019This article describes the clinical features, pathogenesis, prevalence, diagnosis, and management of myotonic dystrophy type 1 and myotonic dystrophy type 2. (Review)
Review
PURPOSE OF REVIEW
This article describes the clinical features, pathogenesis, prevalence, diagnosis, and management of myotonic dystrophy type 1 and myotonic dystrophy type 2.
RECENT FINDINGS
The prevalence of myotonic dystrophy type 1 is better understood than the prevalence of myotonic dystrophy type 2, and new evidence indicates that the risk of cancer is increased in patients with the myotonic dystrophies. In addition, descriptions of the clinical symptoms and relative risks of comorbidities such as cardiac arrhythmias associated with myotonic dystrophy type 1 have been improved.
SUMMARY
Myotonic dystrophy type 1 and myotonic dystrophy type 2 are both characterized by progressive muscle weakness, early-onset cataracts, and myotonia. However, both disorders have multisystem manifestations that require a comprehensive management plan. While no disease-modifying therapies have yet been identified, advances in therapeutic development have a promising future.
Topics: Adult; Female; Humans; Infant, Newborn; Male; Middle Aged; Myotonic Dystrophy
PubMed: 31794466
DOI: 10.1212/CON.0000000000000793 -
International Journal of Molecular... Oct 2022Current studies concerning myotonic dystrophy type 1 (DM1) are in the process of transitioning from molecular investigations to preclinical and clinical trials [...].
Current studies concerning myotonic dystrophy type 1 (DM1) are in the process of transitioning from molecular investigations to preclinical and clinical trials [...].
Topics: Humans; Myotonic Dystrophy
PubMed: 36233257
DOI: 10.3390/ijms231911954 -
Trends in Cardiovascular Medicine May 2020Patients with myotonic dystrophy, the most common neuromuscular dystrophy in adults, have a high prevalence of arrhythmic complications with increased cardiovascular... (Review)
Review
Patients with myotonic dystrophy, the most common neuromuscular dystrophy in adults, have a high prevalence of arrhythmic complications with increased cardiovascular mortality and high risk for sudden death. Sudden death prevention is central and relies on annual follow-up and prophylactic permanent pacing in patients with conduction defects on electrocardiogram and/or infrahisian blocks on electrophysiological study. Implantable cardiac defibrillator therapy may be indicated in patients with ventricular tachyarrhythmia.
Topics: Animals; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Genetic Predisposition to Disease; Humans; Myotonic Dystrophy; Pacemaker, Artificial; Prevalence; Risk Factors; Treatment Outcome
PubMed: 31213350
DOI: 10.1016/j.tcm.2019.06.001 -
JACC. Clinical Electrophysiology Dec 2021
Topics: Cardiac Conduction System Disease; Humans; Myotonic Dystrophy
PubMed: 34949429
DOI: 10.1016/j.jacep.2021.09.017