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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 -
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 -
Continuum (Minneapolis, Minn.) Dec 2013With transition to the genetic era, the number of muscular dystrophies has grown significantly, but so too has our understanding of their pathogenic underpinnings.... (Review)
Review
PURPOSE OF REVIEW
With transition to the genetic era, the number of muscular dystrophies has grown significantly, but so too has our understanding of their pathogenic underpinnings. Clinical features associated with each muscular dystrophy still guide us to the diagnosis. However, improved diagnostic abilities refine and expand phenotypic and genotypic correlates. This article discusses the epidemiology, clinical features, and diagnosis of these disorders.
RECENT FINDINGS
Some important recent advancements include (1) a much greater understanding of the pathogenetic pathways underlying facioscapulohumeral muscular dystrophy and myotonic dystrophy type 1; (2) the publication of diagnostic and treatment guidelines for Duchenne muscular dystrophy; and (3) further clarification of the many genetic muscle disorders presenting a limb-girdle pattern of weakness.
SUMMARY
Muscular dystrophies are genetic, progressive, degenerative disorders with the primary symptom of muscle weakness. Duchenne, Becker, facioscapulohumeral, and myotonic muscular dystrophies are most prevalent and tend to have distinctive features helpful in diagnosis. The limb-girdle, Emery-Dreifuss, and oculopharyngeal muscular dystrophies are less common but often may also be diagnosed on the basis of phenotype. Researchers hope to help patients with future discoveries effective in slowing or halting disease progression, reversing or preventing underlying mechanisms, and repairing previously damaged muscle.
Topics: Humans; Muscular Dystrophies
PubMed: 24305447
DOI: 10.1212/01.CON.0000440659.41675.8b -
Current Opinion in Neurology Oct 2018Muscle and bone are intrinsically linked, and therefore, it is not surprising that many muscular dystrophies are associated with impaired bone health and increased risk... (Review)
Review
PURPOSE OF REVIEW
Muscle and bone are intrinsically linked, and therefore, it is not surprising that many muscular dystrophies are associated with impaired bone health and increased risk of osteoporosis. Osteoporotic fracture is an important and preventable cause of morbidity and mortality. This article will firstly review the general causes of impaired bone health in muscular dystrophies and then focus on the evidence available for the diagnosis and treatment of osteoporosis in specific conditions.
RECENT FINDINGS
With the exception of DMD, there is a paucity of data regarding bone health in muscular dystrophies. However, it appears that in common with all types of muscular dystrophies that cause a significant level of muscle weakness and disability there is an increased risk of falls, fractures and decreased vitamin D levels. A better understanding of the extent of the impaired bone health and underlying causes could help to identify potential new therapeutic agents and aid clinical care.
SUMMARY
It would be prudent for clinicians to assess fracture risk in their muscular dystrophy patients and if appropriate, arrange surveillance and recommend vitamin D supplementation. Additionally, fracture should be considered in any patient presenting with new-onset bone pain.
Topics: Bone Diseases; Bone and Bones; Humans; Muscular Dystrophies; Osteoporotic Fractures; Risk Assessment
PubMed: 30080716
DOI: 10.1097/WCO.0000000000000603 -
Orphanet Journal of Rare Diseases Aug 2006Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide... (Review)
Review
Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years. WWS presents at birth with generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. It is associated with type II cobblestone lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities and congenital muscular dystrophy characterized by hypoglycosylation of alpha-dystroglycan. Several genes have been implicated in the etiology of WWS, and others are as yet unknown. Several mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein (FKRP) genes. Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered alpha-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown. No specific treatment is available. Management is only supportive and preventive.
Topics: Abnormalities, Multiple; Brain; Child, Preschool; Dystrophin; Eye Abnormalities; Female; Glycoproteins; Humans; Infant; Infant, Newborn; Mannosyltransferases; Muscular Dystrophies; Mutation; Pregnancy; Prenatal Diagnosis; Prognosis; Syndrome
PubMed: 16887026
DOI: 10.1186/1750-1172-1-29 -
Matrix Biology : Journal of the... Aug 2018The production of force and power are inherent properties of skeletal muscle, and regulated by contractile proteins within muscle fibers. However, skeletal muscle... (Review)
Review
The production of force and power are inherent properties of skeletal muscle, and regulated by contractile proteins within muscle fibers. However, skeletal muscle integrity and function also require strong connections between muscle fibers and their extracellular matrix (ECM). A well-organized and pliant ECM is integral to muscle function and the ability for many different cell populations to efficiently migrate through ECM is critical during growth and regeneration. For many neuromuscular diseases, genetic mutations cause disruption of these cytoskeletal-ECM connections, resulting in muscle fragility and chronic injury. Ultimately, these changes shift the balance from myogenic pathways toward fibrogenic pathways, culminating in the loss of muscle fibers and their replacement with fatty-fibrotic matrix. Hence a common pathological hallmark of muscular dystrophy is prominent fibrosis. This review will cover the salient features of muscular dystrophy pathogenesis, highlight the signals and cells that are important for myogenic and fibrogenic actions, and discuss how fibrosis alters the ECM of skeletal muscle, and the consequences of fibrosis in developing therapies.
Topics: Animals; Clinical Trials as Topic; Extracellular Matrix; Fibrosis; Humans; Muscle, Skeletal; Muscular Dystrophies; Signal Transduction
PubMed: 29408413
DOI: 10.1016/j.matbio.2018.01.014 -
Comprehensive Physiology Sep 2018The immune response to acute muscle damage is important for normal repair. However, in chronic diseases such as many muscular dystrophies, the immune response can... (Review)
Review
The immune response to acute muscle damage is important for normal repair. However, in chronic diseases such as many muscular dystrophies, the immune response can amplify pathology and play a major role in determining disease severity. Muscular dystrophies are inheritable diseases that vary tremendously in severity, but share the progressive loss of muscle mass and function that can be debilitating and lethal. Mutations in diverse genes cause muscular dystrophy, including genes that encode proteins that maintain membrane strength, participate in membrane repair, or are components of the extracellular matrix or the nuclear envelope. In this article, we explore the hypothesis that an important feature of many muscular dystrophies is an immune response adapted to acute, infrequent muscle damage that is misapplied in the context of chronic injury. We discuss the involvement of the immune system in the most common muscular dystrophy, Duchenne muscular dystrophy, and show that the immune system influences muscle death and fibrosis as disease progresses. We then present information on immune cell function in other muscular dystrophies and show that for many muscular dystrophies, release of cytosolic proteins into the extracellular space may provide an initial signal, leading to an immune response that is typically dominated by macrophages, neutrophils, helper T-lymphocytes, and cytotoxic T-lymphocytes. Although those features are similar in many muscular dystrophies, each muscular dystrophy shows distinguishing features in the magnitude and type of inflammatory response. These differences indicate that there are disease-specific immunomodulatory molecules that determine response to muscle cell damage caused by diverse genetic mutations. © 2018 American Physiological Society. Compr Physiol 8:1313-1356, 2018.
Topics: Humans; Muscular Dystrophies, Limb-Girdle; Muscular Dystrophy, Duchenne; Muscular Dystrophy, Facioscapulohumeral
PubMed: 30215857
DOI: 10.1002/cphy.c170052 -
Journal of Medical Genetics Oct 1989Emery-Dreifuss muscular dystrophy is characterised by the triad of (1) early contractures of the elbows, Achilles tendons, and postcervical muscles; (2) slowly... (Review)
Review
Emery-Dreifuss muscular dystrophy is characterised by the triad of (1) early contractures of the elbows, Achilles tendons, and postcervical muscles; (2) slowly progressive muscle wasting and weakness with a humeroperoneal distribution in the early stages; and (3) a cardiomyopathy usually presenting as heart block. The early recognition of the condition is essential because the insertion of a cardiac pacemaker can be life saving. The disorder is usually inherited as an X linked recessive trait (linked to DNA markers around Xq28). However, occasionally it can be inherited as an autosomal dominant trait and there is an indication that this and the X linked form may in some cases have a neurogenic basis. For these reasons it has recently been proposed that the appellation 'Emery-Dreifuss syndrome' be used for this triad of symptoms and signs.
Topics: Cardiomyopathies; Diagnosis, Differential; Genes, Dominant; Genetic Linkage; Humans; Male; Muscular Dystrophies; Prognosis; Syndrome; X Chromosome
PubMed: 2685312
DOI: 10.1136/jmg.26.10.637