Muscular dystrophies are primary diseases of muscle due to mutations in more than 40 genes, which result in dystrophic changes on muscle biopsy. Unfortunately, gene replacement strategies are not indicated for treating dominant diseases, where reduction or elimination of an abnormal allele would be needed, and as a result, gene therapies for dominant muscular dystrophies have lagged behind. Their inheritance is either autosomal dominant lgmd1 or. Weakness is mainly proximal and the muscular dystrophies alan e h emery seminar the muscular dystrophies are inherited myogenic disorders characterised by progressive muscle wasting and weakness of variable distribution and severity.
It is now well known that all forms of muscular dystrophies are genetic. An improved understanding of their molecular bases has led to more accurate definitions of the clinical features associated with known subtypes. The cumulative evidence suggests that an abnormal muscle surface membrane is the most likely, but this has not been proven. In early stages the muscle biopsy may just reveal a myopathic picture without clear dystrophic features. A pathognomonic pattern characteristic of inclusion body. Duchenne muscular dystrophy dmd is highlighted as the most common and most rapidly progressive muscular dystrophy, with most patients losing the ability to walk by 12 years of age and requiring ventilatory support by 25 years of age. Pdf the inherited myopathies and muscular dystrophies are a diverse group of muscle diseases. The most well known of the muscular dystrophies is duchenne muscular dystrophy dmd, followed by becker muscular dystrophy bmd. In early stages the muscle biopsy may just reveal a myopathic picture without clear dystrophic features, but the clinical context and morphology are able.
Mammen, md, phd the limbgirdle muscular dystrophies 25 matthew p. A unifying feature of the dystrophies is the histological analysis of muscle samples which typically includes variations in fibre size, areas of muscle necrosis, and, ultimately, increased amounts of fat and connective tissue. Listed below are the 9 different types of muscular dystrophy. Neoepitope peptides as biomarkers of disease progression for. The pattern of weakness, tempo of evolution, and mode of inheritance vary among different dystrophies. Neoepitope peptides as biomarkers of disease progression for muscular dystrophies and other myopathies. Muscular dystrophies investigations bmj best practice.
From the department of neurology, college of physicians and surgeons, columbia university, and the neurological institute, columbiapresby terian medical center received for publication july 11, 1958. Jul 22, 2016 overall 167 unrelated patients presenting nmd falling into categories of muscular dystrophies, congenital muscular dystrophies, congenital myopathies, distal myopathies, and other myopathies were tested by targeted ngs of 42 known nmd. Three major theories have been proposed to explain the pathogenesis of muscular dystrophies. Other organs such as the brain, eyes, and skin may be involved. Despite advances in genetics, the importance of the clinical history and physical examination has increased rather than diminished. The inflammatory process leads to destruction of muscle tissue, and is. Shamanthakamani narendran m u s c u l a r d y s t r o p h y m. The first muscles to be affected by weakness are those of the face, neck, hands, forearms, and feet.
Muscular dystrophies and other muscle diseases basicmedical key. Recent findings historically, diagnoses of congenital muscular dystrophy and congenital myopathy have. Disorders of muscle can be simplified into the following categories. Unlike muscular dystrophies, myopathies usually dont cause muscles to. Dec 16, 2019 muscular dystrophy md is a collective group of inherited noninflammatory but progressive muscle disorders without a central or peripheral nerve abnormality. Other inheritable myopathies cause episodes of muscle weakness or stiffness that are milder and more localized and temporary in nature. The inherited myopathies and muscular dystrophies are a diverse group of muscle diseases presenting with common complaints and physical signs. The muscular dystrophies are inherited myogenic disorders characterised by progressive muscle wasting and weakness of variable distribution and severity. Muscular dystrophy md is a group of more than 30 inherited diseases. Home 20 icd9cm diagnosis codes diseases of the nervous system and sense organs 320389 disorders of the peripheral nervous system 350359 muscular dystrophies and other myopathies 359. Henricson ek, abresch rt, florence jm, eagle m, gappmaier e, et al. Increasing availability of dna analysis has been important in decreasing delay in.
Sep 27, 2016 the panel covers all types of muscular dystrophies, myopathies, and other neuromuscular disorders encompassing more than 300 diseases to date. Other recognized varieties of muscular dystrophies are classified into different groups according to their clinical or genetic similarities. This article summarizes the clinical and genetic aspects of these disorders. Myopathies are disorders with structural changes or functional impairment of muscle and can be differentiated from other diseases of the motor unit e. Congenital muscular dystrophies cmds are overall clinically and genetically heterogeneous neuromuscular disorders with onset at birth or in infancy and in which the muscle biopsy is compatible with the presence of a dystrophic myopathy. Muscular dystrophies and other genetic myopathies oxford. The lgmds comprise a group of genetic myopathies that manifest as chronic progressive weakness of hip and shoulder girdles.
The different types can vary in whom they affect, which muscles they affect, and what the symptoms are. Adult and adolescent onset muscular dystrophies mds are a group of disorders that cause muscle disease myopathy characterized by progressive muscle weakness myasthenia and muscle degeneration atrophy due to mutations in one or more genes required for normal muscle function 21. Muscular dystrophies and other muscle diseases harrison. Us20160008320a1 statins in the treatment of muscular. These conditions can be differentiated from other diseases of the motor unit e. Unfortunately, most of them have very similar clinical presentations and even with thorough clinical evaluation and muscle pathology, a correct diagnosis without genetic testing remains difficult.
Muscular dystrophies and other muscle diseases harrisons. In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. Congenital muscular dystrophies and congenital myopathies. This meaning implies that the primary defect is within the muscle, as opposed to the nerves neuropathies or neurogenic disorders or elsewhere e. Inherited myopathies and muscular dystrophies macpeds. They can be subdivided into several groups, including congenital forms, in accordance with the distribution of predominant muscle weakness. Heterogeneous group of diseases, which do not fit into the above two major categories. Neoepitope peptides as biomarkers of disease progression. Recent findings more than 30 genes have been associated with these diseases, most of which have only been recognized in the past decade. Each type differs in the muscles affected, the age of onset, and its rate of progression.
The disease affects the muscles with definite fiber degeneration but without evidence of morphologic aberrations. For example, limb girdle muscular dystrophy is an umbrella name for a group of diseases which exhibits. Recent findings historically, diagnoses of congenital muscular dystrophy and congenital myopathy. In 1986, mdasupported researchers identified the gene that, when flawed a problem known as a mutation causes dmd. Skeletal muscle diseases, or myopathies, are disorders with structural changes or functional impairment of muscle. These episodes often can be managed through medication, or by careful control of exercise and diet. Muscular dystrophy myopathy limbgirdle fshd myotonic dystrophy. Request pdf muscular dystrophies and other inherited myopathies it is certain that more inherited neuromuscular disorders of dogs and cats will be identified as the ability of practicing. The 6minute walk test and other endpoints in duchenne muscular dystrophy.
Types of muscular dystrophy and neuromuscular diseases. Besides being an issue in the form of cachexia and sarcopenia, it is additionally important in a range of neuromuscular diseases, namely muscular dystrophies, congenital myopathies and myositis. Some types are also associated with problems in other organs. The panel covers all types of muscular dystrophies, myopathies, and other neuromuscular disorders encompassing more than 300 diseases to date. Patients with these conditions share characteristics such as early onset of weakness and severe hypotonia. Pdf inherited myopathies and muscular dystrophies researchgate. Myopathies can be distinguished from other disorders of the motor unit, including the. Modern molecular genetic techniques have made it possible to clarify the genetic mutations responsible for most muscular dystrophies. Findings historically, diagnoses of congenital muscular dystrophy and congenital myopathy have been made by clinical features and histopathology. Over 30 genes causing muscular dystrophy are known presently.
It summarizes the advances in molecular and cell biology, biochemistry, and other biological sciences, with an emphasis on their application to this group of muscle disorders and to their clinical implications. Muscular dystrophies are a heterogeneous group of inherited disorders that share similar clinical features and dystrophic changes on muscle biopsy. Unlike the other muscular dystrophies, the muscle weakness is accompanied by myotonia delayed relaxation of muscles after contraction and by various other nonmuscular symptoms. The inflammatory myopathies are a group of muscle diseases that involve inflammation of the muscles or associated tissues, such as the blood vessels that supply the muscles. Muscular dystrophies and other inherited myopathies. The expansion of the spectrum of limb girdle muscular dystrophies lgmds in recent years means that neurologists need to be familiar with the clinical clues that can help with their diagnosis. Duchennes muscular dystrophy also called pseudo hypertrophic muscular dystrophy. The histopathological features of muscular dystrophies. Neoepitope peptides as biomarkers of disease progression for muscular dystrophies and other myopathies article pdf available august 2016 with 92 reads how we measure reads. Diagnosis depends largely on recognition of phenotype, muscle biopsy, and mutation analysis. The congenital muscular dystrophies cmd and myopathies cm are a diverse group of diseases that share features such as early onset of symptoms in the first year of life, genetic causes, and high risks for restrictive lung disease and orthopedic deformities.
Us20160008320a1 us14798,877 us201514798877a us2016008320a1 us 20160008320 a1 us20160008320 a1 us 20160008320a1 us 201514798877 a us201514798877 a us 201514798877a us 2016008320 a1 us2016008320 a1 us 2016008320a1 authority us united states prior art keywords muscle mdx statin simvastatin mice prior art date 20140714 legal status the legal status is an. The muscular dystrophies are a group of inherited disorders characterised by progressive muscle wasting and weakness. Muscular dystrophies discusses the pathogenesis and treatment prospects for muscular dystrophies. Knowledge of diseasespecific complications, implementation of anticipatory care, and medical advances. An approach to myopathy for the primary care clinician american. Muscular dystrophies are genetically transmitted diseases characterized pathologically by degeneration and loss of myofibers and clinically by inexorably progressive weakness and, many of them, by elevated ck. Some types are named for the affected muscles, including the. When other cranial nerve muscles are weak, causing ptosis or extraocular muscle weakness, the most important disorders to consider include neuromuscular junction disorders, oculopharyngeal muscular dystrophy, mitochondrial myopathies, or some of the congenital myopathies table 462e1. Facts about rare muscular dystrophies muscular dystrophy. Central core myopathy, fsh, limbgirdle muscular dystrophy type 1. In performing manual muscle testing of the upper extremities, it is necessary to. Jul 11, 20 muscular dystrophies muscular dystrophy refers to a group of hereditary progressive diseases each with unique phenotypic and genetic features 16. There are several types of muscular dystrophy and each has differing severities and progressions.
Muscular dystrophies, polymyositis, and other myopathies. The inherited myopathies and muscular dystrophies are a diverse group of muscle diseases. Other symptoms of myopathy can include include muscle cramps, stiffness, and spasm. With advances of molecular genetics, the pathogenesis of some of these conditions has become understood. Muscular dystrophies are a genetically and phenotypically heterogeneous group of progressive muscle diseases. Pathogenic or probably pathogenic sequence changes were identified in 79 patients 47. These mutations impact the function of proteins responsible. The disorders differ in which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin. Longitudinal natural history observations over 48 weeks from a multicenter study.
Myopathy is when the muscle fibers do not function properly. Myopathies can be inherited such as the muscular dystrophies or acquired such as common muscle cramps. Congenital muscular dystrophies cmds are clinically and genetically. Clinically, muscular dystrophies are typically progressive, because the muscles ability to regenerate is eventually lost, leading to progressive weakness, often leading to use of a wheelchair, and eventually death. Muscular dystrophies and other genetic myopathies neurologic. A firstline diagnostic assay for limbgirdle muscular. A patient that presents with muscle weakness can have any of these.
In 1987, the protein associated with this gene was identified and named dystrophin. Mitochondrial myopathies muscular dystrophies myotonias acquired druginduced myopathies endocrine myopathies. The myopathies are neuromuscular disorders in which the primary symptom is muscle weakness due to dysfunction of muscle fiber. A myopathy is a muscle disease, and inflammation is a response to cell damage. These mutations impact the function of proteins responsible for giving the muscle structural. Rnai therapy for dominant muscular dystrophies and other. Diseases characterized by muscular weakness in early infancy typically obvious at birth and elevated ck in neonatal period normalizes by 610 wks. Until the 1980s, little was known about the cause of any kind of muscular dystrophy. Congenital muscular dystrophy and congenital myopathy. Muscular dystrophies muscular dystrophy refers to a group of hereditary progressive diseases each with unique phenotypic and genetic features 16. Other inheritable myopathies cause epi sodes of muscle weakness or stiffness that are milder and more localized and temporary in nature. Disease bioinformatics muscular dystrophies and myopathies is a group of conditions that weaken muscles and hinder movement.
Facts about myopathies muscular dystrophy association. Pathogenesis of muscular dystrophies jama neurology jama. Mar 27, 2019 the myopathies are neuromuscular disorders in which the primary symptom is muscle weakness due to dysfunction of muscle fiber. From the department of neurology, college of physicians and surgeons, columbia university, and the neurological institute, columbiapresby terian. Overall 167 unrelated patients presenting nmd falling into categories of muscular dystrophies, congenital muscular dystrophies, congenital myopathies, distal myopathies, and other myopathies were tested by targeted ngs of 42 known nmd.