Muscular dystrophies and other genetic myopathies

2018 ◽  
Author(s):  
Stefen Brady ◽  
David Hilton-Jones
Keyword(s):  
Molecular Genetic ◽  
Immunosuppressive Treatment ◽  
Clinical History ◽  
Muscular Dystrophies ◽  
Genetic Mutations ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Diagnostic Confusion ◽  
Genetic Techniques ◽  
Diagnostic Investigations

Muscular dystrophies are a genetically and phenotypically heterogeneous group of progressive muscle diseases. Modern molecular genetic techniques have made it possible to clarify the genetic mutations responsible for most muscular dystrophies. Despite advances in genetics, the importance of the clinical history and physical examination has increased rather than diminished. It is only through correctly identifying the clinical features that the appropriate diagnostic investigations will be performed. Although muscular dystrophies are typically slowly progressive disorders in which muscle atrophy and weakness are the defining characteristics, diagnostic confusion with the idiopathic inflammatory myopathies (IIM) can occur, and a diagnosis of muscular dystrophy may be considered only after the failure of immunosuppressive treatment for a presumed case of IIM. This chapter reviews the various muscular dystrophies, and discusses how to differentiate between them and the IIM.

scholarly journals Role of Myokines in Myositis Pathogenesis and Their Potential to be New Therapeutic Targets in Idiopathic Inflammatory Myopathies

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Vlad Mageriu ◽  
Emilia Manole ◽  
Alexandra E. Bastian ◽  
Florica Staniceanu
Keyword(s):  
Skeletal Muscle ◽  
Inflammatory Process ◽  
Immunosuppressive Treatment ◽  
Therapeutic Targets ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Autoimmune Process ◽  
Antagonistic Action ◽  
Scientific Approach

Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of autoimmune diseases whose treatment is often a challenge. Many patients, even after immunosuppressive therapy, do not respond to treatment, so new alternatives have been sought for this. Therefore, other signaling pathways that could contribute to the pathogenesis of myositis have been investigated, such as the expression of myokines in skeletal muscle in response to the inflammatory process. In this review, we will refer to these muscle cytokines that are overexpressed or downregulated in skeletal muscle in patients with various forms of IIM, thus being able to contribute to the maintenance of the autoimmune process. Some muscle cytokines, through their antagonistic action, may be a helpful contributor to the disease modulation, and thus, they could represent personalized treatment targets. Here, we consider the main myokines involved in the pathogenesis of myositis, expressing our view on the possibility of using them as potential therapeutic targets: interleukins IL-6, IL-15, and IL-18; chemokines CXCL10, CCL2, CCL3, CCL4, CCL5, and CCL20; myostatin; follistatin; decorin; osteonectin; and insulin-like 6. An interesting topic regarding the complex connection between myokines and noninflammatory pathways implied in IIM has also been briefly described, because it is an important scientific approach to the pathogenesis of IIM and can be a therapeutic alternative to be considered, especially for the patients who do not respond to immunosuppressive treatment.

scholarly journals Genetic Defects Underlie the Non-syndromic Autosomal Recessive Intellectual Disability (NS-ARID)

2017 ◽  
Vol 12 (1) ◽  
pp. 167-177
Author(s):  
Shamim Saleha ◽  
Muhammad Sajid ◽  
Shaista Zafar ◽  
Neelam Pervaiz
Keyword(s):  
Intellectual Disability ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Neurodevelopmental Disorder ◽  
Molecular Genetic ◽  
Family Health ◽  
Genetic Mutations ◽  
Genetic Defects ◽  
Genetic Etiology ◽  
Genetic Techniques

AbstractIntellectual disability (ID) is a neurodevelopmental disorder which appears frequently as the result of genetic mutations and may be syndromic (S-ID) or non-syndromic (NS-ID). ID causes an important economic burden, for patient's family, health systems, and society. Identifying genes that cause S-ID can easily be evaluated due to the clinical symptoms or physical anomalies. However, in the case of NS-ID due to the absence of co-morbid features, the latest molecular genetic techniques can be used to understand the genetic defects that underlie it. Recent studies have shown that non-syndromic autosomal recessive (NS-ARID) is extremely heterogeneous and contributes much more than X-linked ID. However, very little is known about the genes and loci involved in NS-ARID relative to X-linked ID, and whose complete genetic etiology remains obscure. In this review article, the known genetic etiology of NS-ARID and possible relationships between genes and the associated molecular pathways of their encoded proteins has been reviewed which will enhance our understanding about the underlying genes and mechanisms in NS-ARID.

Biological therapy in idiopathic inflammatory myopathies

2014 ◽  
Vol 155 (1) ◽  
pp. 3-10
Author(s):  
Levente Bodoki ◽  
Melinda Nagy-Vincze ◽  
Zoltán Griger ◽  
Andrea Péter ◽  
Csilla András ◽  
...  
Keyword(s):  
T Cells ◽  
Muscle Weakness ◽  
Biological Therapy ◽  
Therapeutic Options ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Progressive Muscle Weakness ◽  
Immune Mediated ◽  
Novel Therapeutic

Idiopathic inflammatory myopathies are systemic, immune-mediated diseases characterized by proximal, symmetrical, progressive muscle weakness. The aim of this work is to give an overview of the biological therapy used in the treatment of idiopathic inflammatory myopathies. The authors also focus on novel results in the therapy directed against the B- and T-cells. They emphasize the importance of new trials in these diseases which may lead to the introduction of novel therapeutic options in these disorders. Orv. Hetil., 2014, 155(1), 3–10.

Clinical impact of myositis-specific autoantibodies on long-term prognosis of juvenile idiopathic inflammatory myopathies: multicentre study

Rheumatology ◽  
2021 ◽  
Author(s):  
Yuichi Yamasaki ◽  
Norimoto Kobayashi ◽  
Shinji Akioka ◽  
Kazuko Yamazaki ◽  
Shunichiro Takezaki ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Multiple Drug ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Gamma Subunits ◽  
Specific Autoantibody ◽  
Long Term Prognosis ◽  
Using Data ◽  
Drug Free

Abstract Objectives This study aimed to investigate the clinical characteristics, treatment and prognosis of juvenile idiopathic inflammatory myopathies (JIIM) in Japan for each myositis-specific autoantibody (MSA) profile. Methods A multicentre, retrospective study was conducted using data of patients with JIIM at nine paediatric rheumatology centres in Japan. Patients with MSA profiles, determined by immunoprecipitation using stored serum from the active stage, were included. Results MSA were detected in 85 of 96 cases eligible for the analyses. Over 90% of the patients in this study had one of the following three MSA types: anti-melanoma differentiation-associated protein 5 (MDA5) (n = 31), anti-transcriptional intermediary factor 1 alpha and/or gamma subunits (TIF1γ) (n = 25) and anti-nuclear matrix protein 2 (NXP2) (n = 25) antibodies. Gottron papules and periungual capillary abnormalities were the most common signs of every MSA group in the initial phase. The presence of interstitial lung disease (ILD) was the highest risk factor for patients with anti-MDA5 antibodies. Most patients were administered multiple drug therapies: glucocorticoids and MTX were administered to patients with anti-TIF1γ or anti-NXP2 antibodies. Half of the patients with anti-MDA5 antibodies received more than three medications including i.v. CYC, especially patients with ILD. Patients with anti-MDA5 antibodies were more likely to achieve drug-free remission (29 vs 21%) and less likely to relapse (26 vs 44%) than others. Conclusion Anti-MDA5 antibodies are the most common MSA type in Japan, and patients with this antibody are characterized by ILD at onset, multiple medications including i.v. CYC, drug-free remission, and a lower frequency of relapse. New therapeutic strategies are required for other MSA types.

scholarly journals Myositis autoantibodies in a racially diverse population of children with idiopathic inflammatory myopathies

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Megan Mariko Perron ◽  
Natalia Vasquez-Canizares ◽  
Gabriel Tarshish ◽  
Dawn M. Wahezi
Keyword(s):  
Clinical Phenotype ◽  
Laboratory Data ◽  
Small Sample ◽  
Organ Involvement ◽  
Idiopathic Inflammatory Myopathies ◽  
Diverse Population ◽  
Inflammatory Myopathies ◽  
Racially Diverse ◽  
Parametric Testing ◽  
Overlap Myositis

Abstract Background Juvenile idiopathic inflammatory myopathies (JIIMs) is a group of autoimmune disorders, including juvenile dermatomyositis (JDM), juvenile polymyositis (JPM) and overlap myositis, that are characterized by proximal muscle weakness, elevated levels of serum muscle enzymes, and pathognomonic skin findings. While the exact etiology of JIIMs is unclear, the presence of myositis specific autoantibodies (MSAs) have been associated with certain clinical phenotypes, organ involvement and disease prognosis. To date, there have been few studies of the associations between MSA presence and patient ethnicity. It is important to understand the extent to which ethnicity impacts disease manifestations, organ involvement and clinical outcomes. The goal of our study is to determine MSA and myositis associated autoantibody (MAA) presence, clinical phenotype, and disease course in a racially diverse population of pediatric patients with JIIMs. Methods Patients age 2–21 years with a prior diagnosis of JDM, JPM or overlap myositis, who had been tested for MSA/MAA, were eligible for study inclusion. Clinical and laboratory data were collected retrospectively via manual chart review in this single-center study. Descriptive statistics were performed to summarize each variable. Given the small sample size, non-parametric testing was performed using Fischer’s exact test, Wilcoxon rank sum test and Kruskal-Wallis test. Results Thirty one patients were included in the analysis. Race and ethnicity were self-reported as Hispanic (48.4%), white (25.8%), and Black (25.8%). The most prevalent MSAs were anti-MDA5 (25.8%), anti-p155/140 (22.6%) and anti-MJ (19.4%). Presence of autoantibodies (p = 0.04) and pulmonary disease (p = 0.03) were significantly higher in patients of Black or Hispanic descent compared with white descent. Anti-MDA5 antibodies, cutaneous ulceration, cardiopulmonary involvement, hospitalizations and one death were only reported in patients with Black or Hispanic descent. Patients with anti-MDA5 antibodies were more likely to be male (p = 0.04) and to have cutaneous ulceration (p = 0.02). Conclusions This study describes the prevalence of MSA/MAA in a racially diverse group of patients with JIIM and further delineates clinical phenotype and disease complications in these groups. We found a relatively high proportion of children with anti-MDA5 antibodies and described potentially worse clinical courses in children of Black or Hispanic descent. Further investigation is warranted to examine these findings.

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