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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 -
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 -
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 -
Tidsskrift For Den Norske Laegeforening... Apr 2024Myotonic dystrophy type 1 is an autosomal dominant, inherited multiorgan disorder that can affect people of all ages. It is the most prevalent inherited muscular disease... (Review)
Review
Myotonic dystrophy type 1 is an autosomal dominant, inherited multiorgan disorder that can affect people of all ages. It is the most prevalent inherited muscular disease in adults. Late diagnosis points to limited knowledge among the medical community that symptoms other than typical muscular symptoms can dominate. The condition often worsens with each generation and some families are severely affected. Significantly delayed diagnosis means a risk of more serious development of the disorder and inadequate symptomatic treatment. We hope that this clinical review article may lead to more rapid diagnosis and better follow-up of this patient group.
Topics: Myotonic Dystrophy; Humans; Delayed Diagnosis; Adult
PubMed: 38651711
DOI: 10.4045/tidsskr.23.0687 -
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 -
Neuromuscular Disorders : NMD Mar 2018Myotonic dystrophy type 1 (DM1) is a multisystemic disorder with neuromuscular symptoms and brain dysfunctions. Depending on the phenotypic expression, the degree of... (Review)
Review
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder with neuromuscular symptoms and brain dysfunctions. Depending on the phenotypic expression, the degree of cognitive impairment remains heterogeneous, ranging from moderate to severe intellectual disability in the congenital form, to executive, visuospatial and personality dysfunction in the adult-onset form. Studies exploring the cognitive or psychiatric impairments in the childhood form of DM1, characterized by an age of onset between one and ten years, uneventful pre and post natal history and normal development the first year of life, are scarce and show conflicting results in regard to a comorbid diagnosis of Autism Spectrum Disorder (ASD). The aim of the current review is to summarize diagnostic criteria and update the state of the debate regarding comorbidity. Evidence from 9 studies collected in PubMed database (representing a total of 175 cases) focusing on clinical, neuropsychological and neuroimaging domains in childhood DM1 is considered and similarities or differences between childhood DM1 and ASD are identified. Highlighting what is known about the neurocognitive features specific to the childhood-onset form of DM1 could help (1) propose early screening regarding socio-emotional and attentional/executive functions or (2) implement therapeutic programs based on reinforcement of executive skills or social cognition.
Topics: Age of Onset; Autism Spectrum Disorder; Cognition Disorders; Comorbidity; Humans; Myotonic Dystrophy
PubMed: 29361396
DOI: 10.1016/j.nmd.2017.12.006 -
Muscle & Nerve Oct 2020The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1... (Review)
Review
The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography, and genetic confirmation. In the absence of genetic confirmation, the diagnosis is supported by detailed electrophysiological testing, exclusion of other related disorders, and analysis of a variant of uncertain significance if present. Symptomatic treatment with a sodium channel blocker, such as mexiletine, is usually the first step in management, as well as educating patients about potential anesthetic complications.
Topics: Acetazolamide; Age of Onset; Carbonic Anhydrase Inhibitors; Chloride Channels; Electrodiagnosis; Electromyography; Fatigue; Genetic Testing; Humans; Lamotrigine; Mexiletine; Muscle Weakness; Muscle, Skeletal; Myalgia; Myotonia Congenita; Myotonic Disorders; NAV1.4 Voltage-Gated Sodium Channel; Practice Guidelines as Topic; Ranolazine; Sodium Channel Blockers; Voltage-Gated Sodium Channel Blockers
PubMed: 32270509
DOI: 10.1002/mus.26887 -
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 -
Chang Gung Medical Journal Aug 2005Myotonic dystrophies or dystrophia myotonica (DM) is a clinical syndrome that includes myotonic dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2), myotonic... (Review)
Review
Myotonic dystrophies or dystrophia myotonica (DM) is a clinical syndrome that includes myotonic dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2), myotonic dystrophy type 3 (DM3), and so forth. The terminology was recommended by the new nomenclature for myotonic dystrophies of an International Panel for Consensus. Previous studies have shown that DM1 is caused by the expansion of a cytosine-thymine-guanine (CTG) repeat in the DM protein kinase gene on chromosome 19, and DM2 is caused by an expansion of a cytosine-cytosine-thymine-guanine (CCTG) repeat in the zinc finger protein 9 (ZNF9) gene on chromosome 3. Because DM1 and DM2 have very similar clinical presentations, the diagnosis of these two disorders needs to be confirmed by molecular genetic analysis. Recently, DM3 was reported to include a multisystem myotonic disorder with frontotemporal dementia, and a linkage to chromosome 15q21-24. Although the age at onset, disease severity, and cerebral abnormality on a brain magnetic resonance spectrometry may correlate with the number of triplet repeats in the blood cells of DM1, it is too early to reach a conclusion. In Taiwan, the prevalence of DM1 is much lower than in Western countries. Previous studies have shown that the central nervous system symptomatology is correlated mainly with the white matter lesions in the brain MRI, but the CNS manifestations seem unrelated to the numbers of CTG triplet repeats in the blood cells. The inverse correlation between age at onset and CTG repeat length is significant only in patients with small expansions of about 100-250 triplet repeats. Transmission contraction of the repeat size is likely to occur in alleles with large repeats and is associated with paternal transmission. In congenital DM1, individual variability of muscle differentiation does occur, in spite of the same number of CTG repeats in the leukocytes.
Topics: Brain; Humans; Magnetic Resonance Imaging; Myotonic Dystrophy; Myotonin-Protein Kinase; Protein Serine-Threonine Kinases; Trinucleotide Repeats
PubMed: 16265841
DOI: No ID Found -
Neuromuscular Disorders : NMD Mar 1996This mini-review describes proximal myotonic myopathy, a recently delineated, dominantly inherited disorder that is similar to but distinct from myotonic dystrophy.... (Review)
Review
This mini-review describes proximal myotonic myopathy, a recently delineated, dominantly inherited disorder that is similar to but distinct from myotonic dystrophy. Proximal myotonic myopathy is not linked to the gene locus for myotonic dystrophy or to the loci of the genes of the muscle sodium and chloride channels associated with other myotonic disorders. Patients often present with myotonia and peculiar muscle pain in early adulthood and develop weakness of the thigh muscles later in life. Cataracts that are indistinguishable from those in myotonic dystrophy also occur commonly. The gene defect responsible for proximal myotonic myopathy awaits discovery. Because of the clinical similarities between proximal myotonic myopathy and myotonic dystrophy, clarification of the genetic differences will not only shed light on the pathomechanism of proximal myotonic myopathy, but may also increase our understanding of myotonic dystrophy.
Topics: Humans; Myotonic Dystrophy
PubMed: 8664567
DOI: 10.1016/0960-8966(95)00036-4