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Clinics in Chest Medicine Jun 2018Muscular dystrophies represent a complex, varied, and important subset of neuromuscular disorders likely to require the care of a pulmonologist. The spectrum of... (Review)
Review
Muscular dystrophies represent a complex, varied, and important subset of neuromuscular disorders likely to require the care of a pulmonologist. The spectrum of conditions encapsulated by this subset ranges from severe and fatal congenital muscular dystrophies with onset in infancy to mild forms of limb and girdle weakness with onset in adulthood and minimal respiratory compromise. The list and classification of muscular dystrophies are undergoing near-constant revision, based largely on new insights from genetics and molecular medicine. The authors present an overview of the muscular dystrophies, including their basic features, common clinical phenotypes, and important facets of management.
Topics: Humans; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Duchenne; Muscular Dystrophy, Facioscapulohumeral
PubMed: 29779596
DOI: 10.1016/j.ccm.2018.01.004 -
BioMed Research International 2015
Topics: Humans; Muscular Dystrophies
PubMed: 26380274
DOI: 10.1155/2015/456348 -
Journal of Orthopaedic Surgery and... Feb 2022A variety of mutations in the largest human gene, dystrophin, cause a spectrum from mild to severe dystrophin-associated muscular dystrophies. Duchenne (DMD) and Becker... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A variety of mutations in the largest human gene, dystrophin, cause a spectrum from mild to severe dystrophin-associated muscular dystrophies. Duchenne (DMD) and Becker (BMD) muscular dystrophies are located at the severe end of the spectrum that primarily affects skeletal muscle. Progressive muscle weakness in these purely genetic disorders encourages families with a positive history for genetic counseling to prevent a recurrence, which requires an accurate prevalence of the disorder. Here, we provide a systematic review and meta-analysis to determine the prevalence of DMD and BMD worldwide.
METHOD
The current systematic review and meta-analysis was carried out using Cochrane seven-step procedure. After determining the research question and inclusion and exclusion criteria, the MagIran, SID, ScienceDirect, WoS, ProQuest, Medline (PubMed), Embase, Cochrane, Scopus, and Google Scholar databases were searched to find relevant studies using defined keywords and all possible keyword combinations using the AND and OR, with no time limit until 2021. The heterogeneity of studies was calculated using the I test, and the publication bias was investigated using the Begg and Mazumdar rank correlation test. Statistical analysis of data was performed using Comprehensive Meta-Analysis software (version 2).
RESULTS
A total of 25 articles involving 901,598,055 people were included. The global prevalence of muscular dystrophy was estimated at 3.6 per 100,000 people (95 CI 2.8-4.5 per 100,000 people), the largest prevalence in the Americans at 5.1 per 100,000 people (95 CI 3.4-7.8 per 100,000 people). According to the subgroup analysis, the prevalence of DMD and BMD was estimated at 4.8 per 100,000 people (95 CI 3.6-6.3 per 100,000 people) and 1.6 per 100,000 people (95 CI 1.1-2.4 per 100,000 people), respectively.
CONCLUSION
Knowing the precise prevalence of a genetic disorder helps to more accurately predict the likelihood of preventing its occurrence in families. The global prevalence of DMD and BMD was very high, indicating the urgent need for more attention to prenatal screening and genetic counseling for families with a positive history.
Topics: Dystrophin; Humans; Muscle Weakness; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Mutation; Prevalence
PubMed: 35168641
DOI: 10.1186/s13018-022-02996-8 -
Neurologic Clinics Aug 2014The dystrophinopathies Duchenne and Becker muscular dystrophies (DMD and BMD) represent the most common inherited disorders of muscle. Improvements in cardiac care,... (Review)
Review
The dystrophinopathies Duchenne and Becker muscular dystrophies (DMD and BMD) represent the most common inherited disorders of muscle. Improvements in cardiac care, attention to respiratory function, and judicious use of spinal correction surgery have led to increased survival in the DMD population. Meanwhile, advances in molecular therapeutics have led to promising therapies that are in or are entering clinical trials. An understanding of the dystrophinopathies, and recent advances in their molecular diagnosis and treatment, is of benefit to practicing neurologists.
Topics: Dystrophin; Humans; Male; Muscular Dystrophy, Duchenne
PubMed: 25037084
DOI: 10.1016/j.ncl.2014.05.002 -
Lancet (London, England) Nov 2019Muscular dystrophies are primary diseases of muscle due to mutations in more than 40 genes, which result in dystrophic changes on muscle biopsy. Now that most of the... (Review)
Review
Muscular dystrophies are primary diseases of muscle due to mutations in more than 40 genes, which result in dystrophic changes on muscle biopsy. Now that most of the genes responsible for these conditions have been identified, it is possible to accurately diagnose them and implement subtype-specific anticipatory care, as complications such as cardiac and respiratory muscle involvement vary greatly. This development and advances in the field of supportive medicine have changed the standard of care, with an overall improvement in the clinical course, survival, and quality of life of affected individuals. The improved understanding of the pathogenesis of these diseases is being used for the development of novel therapies. In the most common form, Duchenne muscular dystrophy, a few personalised therapies have recently achieved conditional approval and many more are at advanced stages of clinical development. In this Seminar, we concentrate on clinical manifestations, molecular pathogenesis, diagnostic strategy, and therapeutic developments for this group of conditions.
Topics: Humans; Muscular Dystrophies
PubMed: 31789220
DOI: 10.1016/S0140-6736(19)32910-1 -
Continuum (Minneapolis, Minn.) Dec 2019Congenital muscular dystrophies and congenital myopathies are a heterogeneous group of disorders resulting in hypotonia, muscle weakness, and dystrophic or myopathic... (Review)
Review
PURPOSE OF REVIEW
Congenital muscular dystrophies and congenital myopathies are a heterogeneous group of disorders resulting in hypotonia, muscle weakness, and dystrophic or myopathic features on muscle biopsy. This article summarizes the clinical and genetic aspects of these disorders.
RECENT FINDINGS
Historically, diagnoses of congenital muscular dystrophy and congenital myopathy have been made by clinical features and histopathology; however, recent advances in genetics have changed diagnostic practice by relying more heavily on genetic findings. This article reviews the clinical and genetic features of the most common congenital muscular dystrophies including laminin subunit alpha 2 (LAMA2)-related (merosin deficient), collagen VI-related, and α-dystroglycan-related congenital muscular dystrophies and reviews the most common congenital myopathies including nemaline rod, core, and centronuclear myopathies. With the increasing accessibility of genetic testing, the number of genes found to be associated with these disorders has increased dramatically. A wide spectrum of severity and onset (from birth to adulthood) exist across all subtypes. Progression and other features are variable depending on the subtype and severity of the specific genetic mutation.
SUMMARY
Congenital muscular dystrophy and congenital myopathy are increasingly recognized disorders. A growing appreciation for the breadth of phenotypic variability and overlap between established subtypes has challenged long-standing phenotypic and histopathologic classifications of these disorders but has driven a greater understanding of pathogenesis and opened the door to the development of novel treatments.
Topics: Child, Preschool; Female; Humans; Infant; Male; Muscular Dystrophies; Myopathies, Structural, Congenital
PubMed: 31794464
DOI: 10.1212/CON.0000000000000792 -
Disease Models & Mechanisms Feb 2020Skeletal muscle fibres are multinucleated cells that contain postmitotic nuclei (i.e. they are no longer able to divide) and perform muscle contraction. They are formed... (Review)
Review
Skeletal muscle fibres are multinucleated cells that contain postmitotic nuclei (i.e. they are no longer able to divide) and perform muscle contraction. They are formed by fusion of muscle precursor cells, and grow into elongating myofibres by the addition of further precursor cells, called satellite cells, which are also responsible for regeneration following injury. Skeletal muscle regeneration occurs in most muscular dystrophies in response to necrosis of muscle fibres. However, the complex environment within dystrophic skeletal muscle, which includes inflammatory cells, fibroblasts and fibro-adipogenic cells, together with the genetic background of the model and the muscle being studied, complicates the interpretation of laboratory studies on muscular dystrophies. Many genes are expressed in satellite cells and in other tissues, which makes it difficult to determine the molecular cause of various types of muscular dystrophies. Here, and in the accompanying poster, we discuss our current knowledge of the cellular mechanisms that govern the growth and regeneration of skeletal muscle, and highlight the defects in satellite cell function that give rise to muscular dystrophies.
Topics: Animals; Disease; Disease Models, Animal; Health; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Dystrophies
PubMed: 32066552
DOI: 10.1242/dmm.042192 -
Journal of Neuromuscular Diseases 2022Clinical and molecular data on the occurrence and frequency of inherited neuromuscular disorders (NMD) in the Lebanese population is scarce.
BACKGROUND
Clinical and molecular data on the occurrence and frequency of inherited neuromuscular disorders (NMD) in the Lebanese population is scarce.
OBJECTIVE
This study aims to provide a retrospective overview of hereditary NMDs based on our clinical consultations in Lebanon.
METHODS
Clinical and molecular data of patients referred to a multi-disciplinary consultation for neuromuscular disorders over a 20-year period (1999-2019) was reviewed.
RESULTS
A total of 506 patients were diagnosed with 62 different disorders encompassing 10 classes of NMDs. 103 variants in 49 genes were identified. In this cohort, 81.4% of patients were diagnosed with motor neuron diseases and muscular dystrophies, with almost half of these described with spinal muscular atrophy (SMA) (40.3% of patients). We estimate a high SMA incidence of 1 in 7,500 births in Lebanon. Duchenne and Becker muscular dystrophy were the second most frequently diagnosed NMDs (17% of patients). These disorders were associated with the highest number of variants (39) identified in this study. A highly heterogeneous presentation of Limb Girdle Muscular Dystrophy and Charcot-Marie-Tooth disease was notably identified. The least common disorders (5.5% of patients) involved congenital, metabolic, and mitochondrial myopathies, congenital myasthenic syndromes, and myotonic dystrophies. A review of the literature for selected NMDs in Lebanon is provided.
CONCLUSIONS
Our study indicates a high prevalence and underreporting of heterogeneous forms of NMDs in Lebanon- a major challenge with many novel NMD treatments in the pipeline. This report calls for a regional NMD patient registry.
Topics: Adolescent; Adult; Charcot-Marie-Tooth Disease; Child; Child, Preschool; Female; Humans; Infant; Lebanon; Male; Middle Aged; Motor Neuron Disease; Muscular Atrophy, Spinal; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Duchenne; Retrospective Studies; Young Adult
PubMed: 34602496
DOI: 10.3233/JND-210652 -
Cells Sep 2021Plectin is a giant cytoskeletal crosslinker and intermediate filament stabilizing protein. Mutations in the human plectin gene () cause several rare diseases that are... (Review)
Review
Plectin is a giant cytoskeletal crosslinker and intermediate filament stabilizing protein. Mutations in the human plectin gene () 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, 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 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, 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 defects and their downstream effects on the skeletal muscle organization.
Topics: Animals; Epidermolysis Bullosa Simplex; Humans; Muscle, Skeletal; Muscular Dystrophies; Plectin
PubMed: 34572129
DOI: 10.3390/cells10092480 -
Brain and Nerve = Shinkei Kenkyu No... Jun 2022In Japan, medical care for patients with muscular dystrophy has improved through multidisciplinary care provided by specialized institutions, resulting in a marked...
In Japan, medical care for patients with muscular dystrophy has improved through multidisciplinary care provided by specialized institutions, resulting in a marked increase in life expectancy. Today, most patients with muscular dystrophy live in their own homes and receive medical care in various non-specialized institutions. Some muscular dystrophy patients have associated central nervous system disorders, which include neurodevelopmental syndromes. In addition, many patients are physically and mentally unstable during adolescence, when the transition from pediatric neurology to adult neurology occurs. Early opportunities to consult specialized institutions for rehabilitation or specific periods when pediatric and adult neurologists take care of patients together should be considered to facilitate this transition more easily.
Topics: Adolescent; Adult; Child; Humans; Japan; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Neurology; Patient Care
PubMed: 35676214
DOI: 10.11477/mf.1416202121