Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated with mutations in several genes involved in muscular structure and function. Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection. Muscle involvement image pattern differs depending on the limb girdle muscular dystrophy subtype. Muscle involvement is conspicuous at the posterior thigh in calpainopathy and fukutin-related proteinopathy; anterior thigh in sarcoglycanopathy; whole thigh in dysferlinopathy, and telethoninopathy. The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory management. Besides that, it may probably, in the future, provide specific genetic therapies for each subtype.

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Role of MRI in the diagnosis of neuromuscular disorders

Orvosi Hetilap ◽

10.1556/oh.2011.29193 ◽

2011 ◽

Vol 152 (34) ◽

pp. 1362-1367

Author(s):

Endre Pál ◽

Katalin Dérczy

Keyword(s):

Differential Diagnosis ◽

Muscle Damage ◽

Neuromuscular Disease ◽

Neuromuscular Disorders ◽

Whole Body ◽

Muscular Dystrophies ◽

Genetic Tests ◽

Muscle Involvement ◽

Whole Body Mri

Recently, the assessment of the muscles using limb MRI and whole body MRI has become widely available and more frequent. In cases of muscular dystrophies it may help to select the optimal muscles for biopsy, because the severely atrophic and degenerated muscles are not suitable for histological tests. It is also known that the pattern of muscle involvement is characteristic for a certain neuromuscular disease, and clinically silent muscle damage can be visualized, as well. Therefore, imaging of muscles is helpful in neuromuscular differential diagnosis and planning genetic tests. Orv. Hetil., 2011, 152, 1362–1367.

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P.P.4 07 Phenotype and muscle biopsy findings in the first German patient with limb-girdle muscular dystrophy 2K – Important differential diagnosis of Becker muscular dystrophy

Neuromuscular Disorders ◽

10.1016/j.nmd.2006.05.124 ◽

2006 ◽

Vol 16 (9-10) ◽

pp. 680

Author(s):

U. Schara ◽

W. Kress ◽

M. Vorgerd ◽

C. Gross ◽

J. Winkler ◽

...

Keyword(s):

Differential Diagnosis ◽

Muscular Dystrophy ◽

Muscle Biopsy ◽

Becker Muscular Dystrophy ◽

Limb Girdle Muscular Dystrophy ◽

German Patient ◽

Important Differential Diagnosis

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A Novel Mutation in a Large French-Canadian Family with LGMD1B

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s031716710000891x ◽

2008 ◽

Vol 35 (3) ◽

pp. 331-334 ◽

Cited By ~ 9

Author(s):

Nicolas Chrestian ◽

Paul N. Valdmanis ◽

Najmeddine Echahidi ◽

Denis Brunet ◽

Jean-Pierre Bouchard ◽

...

Keyword(s):

Muscular Dystrophy ◽

Muscle Biopsy ◽

Pacemaker Implantation ◽

Limb Girdle Muscular Dystrophy ◽

Cardiac Conduction ◽

Cardiac Complications ◽

French Canadian ◽

New Mutation ◽

Muscle Involvement ◽

Phenotypic Spectrum

ABSTRACTBackground:Limb girdle muscular dystrophy type 1B is an autosomal dominant disease characterized by late onset proximal muscle involvement associated with cardiac complications such as atrioventricular conduction blocks, dilated cardiomyopathy, and sudden death.Objective:Define the full phenotypic spectrum of a new mutation in the LMNA gene causing limb girdle muscular dystrophy type 1B.Methods:We identified a large French Canadian family with the LGMD 1B phenotype and a cardiac conduction disease phenotype that carried a new mutation in the LMNA gene and sought to define its full phenotypic spectrum by performing complete neurological and cardiac evaluations, muscle biopsy, RNA and DNA studies.Results:The proband and 12 living at risk relatives were tested. In total, we identified seven carriers of a new (IVS9-3C>G) LMNA gene mutation. Of the three symptomatic patients, all had cardiac involvement, but only two presented proximal limb weakness. The one available muscle biopsy demonstrated a normally expressed lamin A/C protein, localized at the nuclear envelope. RNA study revealed a loss of exon 10 transcription caused by the IVS9-3C to G splicing mutation.Conclusions:We have identified a new mutations in the LMNA gene in a French-Canadian family. This diagnosis has important implications for affected patients and their siblings since they may eventually require pacemaker implantation.

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Axial muscle involvement in patients with Limb girdle muscular dystrophy type R9

Muscle & Nerve ◽

10.1002/mus.27491 ◽

2022 ◽

Author(s):

Karoline Lolk Revsbech ◽

Karen Rudolf ◽

Aisha Munawar Sheikh ◽

Tahmina Khawajazada ◽

Josefine Stricker Borch ◽

...

Keyword(s):

Muscular Dystrophy ◽

Limb Girdle Muscular Dystrophy ◽

Muscle Involvement ◽

Axial Muscle

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Respiratory muscle imaging by ultrasound and MRI in neuromuscular disorders

European Respiratory Journal ◽

10.1183/13993003.00137-2021 ◽

2021 ◽

pp. 2100137

Author(s):

Jeroen L.M. van Doorn ◽

Francesca Pennati ◽

Hendrik H.G. Hansen ◽

Baziel G.M. van Engelen ◽

Andrea Aliverti ◽

...

Keyword(s):

Respiratory Muscle ◽

Imaging Techniques ◽

Neuromuscular Disorders ◽

Respiratory Muscles ◽

Daily Practice ◽

Structure And Function ◽

Muscle Structure ◽

Respiratory Management ◽

Technological Developments ◽

And Function

Respiratory muscle weakness is common in neuromuscular disorders and leads to significant respiratory difficulties. Therefore, reliable and easy assessment of respiratory muscle structure and function in neuromuscular disorders is crucial. In the last decade, ultrasound and MRI emerged as promising imaging techniques to assess respiratory muscle structure and function. Respiratory muscle imaging directly measures the respiratory muscles and, in contrast to pulmonary function testing, is independent of patient effort. This makes respiratory muscle imaging suitable to use as tool in clinical respiratory management and as outcome parameter in upcoming drug trials for neuromuscular disorders, particularly in children. In this narrative review, we discuss the latest studies and technological developments in imaging of the respiratory muscles by US and MR, and its clinical application and limitations. We aim to increase understanding of respiratory muscle imaging and facilitate its use as outcome measure in daily practice and clinical trials.

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Differential diagnosis of Duchenne muscular dystrophy

L.O. Badalyan Neurological Journal ◽

10.46563/2686-8997-2021-2-3-159-166 ◽

2021 ◽

Vol 2 (3) ◽

pp. 159-166

Author(s):

Alexey L. Kurenkov ◽

Lyudmila M. Kuzenkova ◽

Lale A. Pak ◽

Bella I. Bursagova ◽

Tatyana V. Podkletnova ◽

...

Keyword(s):

Differential Diagnosis ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Muscle Damage ◽

Genetic Diagnosis ◽

Clinical Manifestations ◽

Neuromuscular Diseases ◽

Muscular Dystrophies ◽

Juvenile Form ◽

Pathogenic Variants

Duchenne muscular dystrophy (DMD) is a disease with an X-linked recessive type of inheritance, belonging to a group of disorders with primary muscle damage, caused by pathogenic variants in the DMD gene and associated with dysfunction of the dystrophin protein. Since DMD is manifested by the gradual development of progressive, mainly proximal muscle weakness, the differential diagnosis is primarily carried out in the group of diseases with muscle damage - myopathies. Among these diseases, the leading candidates for differential diagnosis are hereditary myopathies (limb-girdle muscular dystrophies, facioscapulohumeral dystrophy, congenital muscular dystrophies, glycogenoses - the most common juvenile form of glycogenosis type II (Pompe disease)) and, much less often, congenital myopathies and other conditions of neuromuscular diseases). When conducting a differential diagnosis in a child with suspected DMD, the age of the onset of the disease, early initial clinical manifestations and the development of symptoms as they grow, genealogical analysis, laboratory tests (the level of creatine kinase, aspartate aminotransferase, alanine aminotransferase in blood serum), instrumental (electromyography, magnetic resonance imaging of the brain and muscles) and molecular genetics (polymerase chain reaction, multiplex ligation-dependent probe amplification, next-generation sequencing, Sanger sequencing, etc.) of studies, and in some cases, muscle biopsy data. Knowledge of the nuances of the differential diagnosis allows establishing a genetic diagnosis of DMD as early as possible, which is extremely important for the formation of the prognosis of the disease and the implementation of all available treatment methods, including pathogenetic therapy, and is also necessary for medical and genetic counselling of families with DMD patients.

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The use of ivabradine in a patient with inappropriate sinus tachycardia and cardiomyopathy due to limb girdle muscular dystrophy type 2I

BMJ Case Reports ◽

10.1136/bcr-2019-230647 ◽

2020 ◽

Vol 13 (1) ◽

pp. e230647

Author(s):

Rajkumar Rajendram ◽

Fahad AlDhahri ◽

Naveed Mahmood ◽

Mubashar Kharal

Keyword(s):

Skeletal Muscle ◽

Muscular Dystrophy ◽

Cardiac Disease ◽

Sinus Tachycardia ◽

Prognostic Significance ◽

Mechanisms Of Action ◽

Limb Girdle Muscular Dystrophy ◽

Muscular Dystrophies ◽

Appropriate Use ◽

Inappropriate Sinus Tachycardia

Muscular dystrophies are a heterogeneous group of disorders that commonly involve cardiac and skeletal muscle. Comprehensive guidelines for the management of cardiac failure and arrhythmias are available. However, the studies from which their recommendations are derived did not include any patients with muscular dystrophy. Some medications (eg, betablockers) may have significant side effects in this cohort. In some situations the use of agents with unique mechanisms of action such as ivabradine (a ‘funny’ channel inhibitor) may be more appropriate. Use of ivabradine has not previously been reported in limb girdle muscular dystrophy (LGMD). We describe the course of a patient with LGMD type 2I, cardiomyopathy and inappropriate sinus tachycardia treated with ivabradine. As advances in respiratory support have improved the outcomes of patients with muscular dystrophy; the prognostic significance of cardiac disease has increased. Ivabradine is tolerated and may reduce symptoms, morbidity and mortality in this cohort.

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The Duchenne muscular dystrophy gene and cancer

Cellular Oncology ◽

10.1007/s13402-020-00572-y ◽

2020 ◽

Author(s):

Leanne Jones ◽

Michael Naidoo ◽

Lee R. Machado ◽

Karen Anthony

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Muscle Protein ◽

Neuromuscular Disorders ◽

Becker Muscular Dystrophy ◽

Gene Products ◽

Large Gene ◽

Cancer Types ◽

And Function ◽

Dystrophin Protein

Abstract Background Mutation of the Duchenne muscular dystrophy (DMD) gene causes Duchenne and Becker muscular dystrophy, degenerative neuromuscular disorders that primarily affect voluntary muscles. However, increasing evidence implicates DMD in the development of all major cancer types. DMD is a large gene with 79 exons that codes for the essential muscle protein dystrophin. Alternative promotor usage drives the production of several additional dystrophin protein products with roles that extend beyond skeletal muscle. The importance and function(s) of these gene products outside of muscle are not well understood. Conclusions We highlight a clear role for DMD in the pathogenesis of several cancers, including sarcomas, leukaemia’s, lymphomas, nervous system tumours, melanomas and various carcinomas. We note that the normal balance of DMD gene products is often disrupted in cancer. The short dystrophin protein Dp71 is, for example, typically maintained in cancer whilst the full-length Dp427 gene product, a likely tumour suppressor, is frequently inactivated in cancer due to a recurrent loss of 5’ exons. Therefore, the ratio of short and long gene products may be important in tumorigenesis. In this review, we summarise the tumours in which DMD is implicated and provide a hypothesis for possible mechanisms of tumorigenesis, although the question of cause or effect may remain. We hope to stimulate further study into the potential role of DMD gene products in cancer and the development of novel therapeutics that target DMD.

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