RESUMO
Myopathies represent a wide spectrum of heterogeneous diseases mainly characterized by the abnormal structure or functioning of skeletal muscle. The current paper provides a comprehensive overview of cognitive deficits observed in various myopathies by consulting the main libraries (Pubmed, Scopus and Google Scholar). This review focuses on the causal classification of myopathies and concomitant cognitive deficits. In most studies, cognitive deficits have been found after clinical observations while lesions were also present in brain imaging. Most studies refer to hereditary myopathies, mainly Duchenne muscular dystrophy (DMD), and myotonic dystrophies (MDs); therefore, most of the overview will focus on these subtypes of myopathies. Most recent bibliographical sources have been preferred.
Assuntos
Disfunção Cognitiva/etiologia , Distrofia Muscular de Duchenne/complicações , Distrofia Miotônica/complicações , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Humanos , Distrofia Muscular de Duchenne/classificação , Distrofia Muscular de Duchenne/genética , Distrofia Miotônica/classificação , Distrofia Miotônica/genéticaRESUMO
Duchenne muscular dystrophy (DMD) is a progressive, fatal pediatric disorder with significant burden on parents. Assessing disease impact can inform clinical interventions. Best-worst scaling (BWS) was used to elicit parental priorities among 16 short-term, DMD-related worries identified through community engagement. Respondents viewed 16 subsets of worries, identified using a balanced, incomplete block design, and identified the most and least worrying items. Priorities were assessed using best-worst scores (spanning +1 to -1) representing the relative number of times items were endorsed as most and least worrying. Independent-sample t-tests compared prioritization of parents with ambulatory and non-ambulatory children. Participants (n = 119) most prioritized worries about weakness progression (BW score = 0.64) and getting the right care over time (BW = 0.25). Compared to parents of non-ambulatory children, parents of ambulatory children more highly prioritized missing treatments (BW = 0.31 vs. 0.13, p < 0.001) and being a good enough parent (BW = 0.06 vs. -0.08, p = 0.010), and less prioritized child feeling like a burden (BW = -0.24 vs. -0.07, p < 0.001). Regardless of child's disease stage, caregiver interventions should address the emotional impact of caring for a child with a progressive, fatal disease. We demonstrate an accessible, clinically-relevant approach to prioritize disease impact using BWS, which offers an alternative to the use of traditional rating/ranking scales.
Assuntos
Ansiedade/diagnóstico , Ansiedade/psicologia , Distrofia Muscular de Duchenne/classificação , Distrofia Muscular de Duchenne/genética , Pais/psicologia , Perfil de Impacto da Doença , Atividades Cotidianas/classificação , Atividades Cotidianas/psicologia , Adulto , Criança , Pré-Escolar , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/psicologia , Poder Familiar/psicologia , Prognóstico , Psicometria , Reprodutibilidade dos TestesRESUMO
Achondroplasia, Duchenne muscular dystrophy, and osteogenesis imperfecta are among the most frequent rare genetic disorders affecting the musculoskeletal system in children. Rare genetic disorders are severely disabling and can have substantial impacts on families, children, and on healthcare systems. This literature review aims to classify, summarize and compare these non-medical impacts of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.
Assuntos
Acondroplasia/classificação , Proteção da Criança , Distrofia Muscular de Duchenne/classificação , Osteogênese Imperfeita/classificação , Acondroplasia/genética , Acondroplasia/terapia , Criança , Humanos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/terapia , Qualidade de VidaRESUMO
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) phenotypes are used to describe disease progression in affected individuals. However, considerable heterogeneity has been observed across and within these two phenotypes, suggesting a spectrum of severity rather than distinct conditions. Characterizing the phenotypes and subphenotypes aids researchers in the design of clinical studies and clinicians in providing anticipatory guidance to affected individuals and their families. Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), we used K-means cluster analysis to group phenotypically similar males with pediatric-onset dystrophinopathy. We identified four dystrophinopathy clusters: Classical BMD, Classical DMD, late ambulatory DMD, and severe DMD. The clusters that we identified align with both 'classical' and 'non-classical' dystrophinopathy described in the literature. Individuals with dystrophinopathies have heterogenous clinical presentations that cluster into phenotypically similar groups. Use of clinically-derived phenotyping may provide a clearer understanding of disease trajectories, reduce variability in study results, and prevent exclusion of certain cohorts from analysis. Findings from studying subphenotypes may ultimately improve our ability to predict disease progression.
Assuntos
Distrofia Muscular de Duchenne/classificação , Distrofia Muscular de Duchenne/fisiopatologia , Idade de Início , Criança , Pré-Escolar , Análise por Conglomerados , Humanos , Masculino , FenótipoRESUMO
INTRODUCTION: We carried out a population-based study of dystrophin mutations in patients followed by members of the Canadian Paediatric Neuromuscular Group (CPNG) over a ten-year period. OBJECTIVES: We aimed to describe the changes in diagnostic testing for dystrophinopathy and to determine the frequency of dystrophin mutations from 2000 to 2009. METHODS: De-identified data containing the clinical phenotypes, diagnostic methods, and mutational reports from dystrophinopathy patients followed by CPNG centres from January 2000 to December 2009 were analyzed using descriptive statistics. RESULTS: 773 patients had a confirmed diagnosis of dystrophinopathy based on genetic testing (97%), muscle biopsy (2%), or family history (1%). 573 (74%) had complete deletion/duplication analysis of all 79 exons or whole gene sequencing, resulting in 366 (64%) deletions, 64 (11%) duplications, and 143 (25%) point mutations. The percentage of patients who were diagnosed using currently accepted genetic testing methods varied across Canada, with a mean of 63% (SD 23). 246 (43%) mutations involved exons 45 to 53. The top ten deletions (n=147, 26%) were exons 45-47, 45-48, 45, 45-50, 45-55, 51, 45-49, 45-52, 49-50, and 46-47. 169 (29%) mutations involved exons 2 to 20. The most common duplications (n=29, 5.1%) were exons 2, 2-7, 2-17, 3-7, 8-11, 10, 10-11, and 12. CONCLUSION: This is the most comprehensive report of dystrophin mutations in Canada. Consensus guidelines regarding the diagnostic approach to dystrophinopathy will hopefully reduce the geographical variation in mutation detection rates in the coming decade.
Assuntos
Distrofina/genética , Distrofia Muscular de Duchenne/epidemiologia , Distrofia Muscular de Duchenne/genética , Mutação/genética , Canadá , Planejamento em Saúde Comunitária , Éxons/genética , Feminino , Testes Genéticos/métodos , Humanos , Estudos Longitudinais , Masculino , Distrofia Muscular de Duchenne/classificação , Distrofia Muscular de Duchenne/diagnóstico , Fenótipo , Prevalência , Estudos Retrospectivos , Estatística como Assunto , Fatores de TempoRESUMO
BACKGROUND: The aim of this study was to compare the electromyographic pattern in Becker muscular dystrophy (BMD) with that found in Duchenne muscular dystrophy (DMD). MATERIAL AND METHOD: Fourteen men with BMD and 51 boys with DMD were investigated. Proximal muscles were examined: m. biceps brachii (BB) and m. rectus femoris (RF). They were divided according to the clinical criteria in two groups: of those with slight changes (group AB) and of those with severe abnormalities (CD). As in the Part I of the paper our own method of Functional-QEMG was applied in the CNEMG examination. RESULTS AND CONCLUSIONS: Spontaneous activity (fibrillations, complex repetitive discharges) was equally frequent in BMD and DMD. Linked potentials were rather frequent in either group. Myopathic features such as MUAPs low amplitude and area, polyphasic shape were seen in either condition, but more marked in DMD than in BMD. Evaluation of IP recordings revealed that IP amplitude (amplitude size) is low in DMD already at the early stage of lesion but normal or only slightly diminished in BMD. It might perhaps suggest different degrees of lesion in type II MUs between the compared types of muscular dystrophy.
Assuntos
Eletromiografia , Músculo Esquelético/fisiopatologia , Distrofia Muscular de Duchenne/classificação , Distrofia Muscular de Duchenne/fisiopatologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Contração Muscular/fisiologiaRESUMO
Dystrophinopathies are caused by mutations in DMD resulting in progressive muscle weakness. They are historically divided into the more severe Duchenne (DMD) and milder Becker (BMD) muscular dystrophy phenotypes. Classification is important for research and clinical care. The purpose of this study was to describe a multi-variable approach to classifying cases from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) and to assess the accuracy of the diagnostic classification scheme. We used age at loss of mobility, molecular testing results, and age at symptom onset to classify cases as having DMD or BMD and to assess sensitivity and specificity. Mobility status showed low sensitivity and high specificity for predicting DMD (65.5% and 99.3%, respectively) and BMD (62.8% and 97.7%, respectively) phenotypes. Molecular testing showed 90.9% sensitivity and 66.4% specificity for DMD; 76.3% sensitivity and 90.0% specificity for BMD. Age of onset predicted DMD with sensitivity of 73.9% and specificity of 69.0%; BMD had 99.7% specificity and 36.7% sensitivity. Mobility status, molecular test results, and age at symptom onset are important but inconsistent measures for accurately classifying individuals into DMD or BMD phenotypes. These results have implications for prognosis in newly diagnosed individuals and for classifying phenotype in clinical trials.
Assuntos
Distrofia Muscular de Duchenne/classificação , Distrofia Muscular de Duchenne/diagnóstico , Adulto , Bases de Dados Factuais , Humanos , Masculino , Prontuários Médicos , Fenótipo , Adulto JovemRESUMO
There exists much phenotypic heterogeneity in Duchenne muscular dystrophy and its allelic variant, Becker muscular dystrophy. The molecular findings on 53 patients with Duchenne and 15 patients with Becker type muscular dystrophy in KwaZulu Natal, South Africa are reported. Multiplex PCR was performed using primers targeting 18 hot-spot exons throughout the dystrophin gene. Analysis of the multiplex PCR data revealed that 39/68 (57.0%) patients included in the study showed a deletion (33 DMD and 6 BMD patients). Twenty-five patients were Black, 4 were White and 10 were Indian. Using the Chamberlain and Beggs multiplex PCR assays, the region of the genome most frequently affected by a deletion includes exons 47-51. The distal region of the dystrophin gene was most frequently affected by the deletion in both Black and Indian patients. There were too few White patients for conclusions to be drawn concerning the most frequently affected part of the gene. Although the numbers are insufficient to determine whether ethnic differences are present, the Chamberlain and Beggs multiplex PCR assays detect deletions with the same frequency in South African DMD/BMD patients as that reported in the literature.
Assuntos
Distrofina/genética , Deleção de Genes , Distrofia Muscular de Duchenne/genética , Éxons , Feminino , Humanos , Masculino , Distrofia Muscular de Duchenne/classificação , Distrofia Muscular de Duchenne/epidemiologia , Reação em Cadeia da Polimerase/métodos , África do Sul/epidemiologia , África do Sul/etnologiaRESUMO
Neuromuscular diseases represent a rare cause of dilated myocardiopathy, among them Duchenne muscular dystrophy is the most common. Transthoracic echocardiography and cardiac magnetic resonance imaging can assess cardiac involvement early. The case of a patient diagnosed with Duchenne muscular dystrophy who develops cardiac involvement during cardiology follow-up is presented below.
Assuntos
Humanos , Masculino , Adulto , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , Cardiomiopatia Dilatada , Distrofina/genética , Distrofia Muscular de Duchenne/classificação , Distrofia Muscular de Duchenne/fisiopatologia , Diagnóstico Diferencial , Insuficiência CardíacaRESUMO
High variability in patients' changes in 6 minute walk distance (6MWD) over time has complicated clinical trials of treatment efficacy in Duchenne muscular dystrophy (DMD). We assessed whether boys with DMD could be grouped into classes that shared similar ambulatory function trajectories as measured by 6MWD. Ambulatory boys aged 5 years or older with genetically confirmed DMD who were enrolled in a natural history study at 11 care centers throughout Italy were included. For each boy, standardized assessments of 6MWD were available at annual intervals spanning 3 years. Trajectories of 6MWD vs. age and trajectories of 6MWD vs. time from enrollment were examined using latent class analysis. A total of 96 boys were included. At enrollment, the mean age was 8.3 years (mean 6MWD: 374 meters). After accounting for age, baseline 6MWD, and steroid use, four latent trajectory classes were identified as explaining 3-year 6MWD outcomes significantly better than a single average trajectory. Patient trajectories of 6MWD change from enrollment were categorized as having fast decline (n = 25), moderate decline (n = 19), stable function (n = 37), and improving function (n = 15) during the 3-year follow-up. After accounting for trajectory classes, the standard deviation of variation in 6MWD was reduced by approximately 40%. The natural history of ambulatory function in DMD may be composed of distinct trajectory classes. The extent to which trajectories are associated with novel and established prognostic factors warrants further study. Reducing unexplained variation in patient outcomes could help to further improve DMD clinical trial design and analysis.
Assuntos
Distrofia Muscular de Duchenne/classificação , Distrofia Muscular de Duchenne/fisiopatologia , Caminhada , Adolescente , Fatores Etários , Criança , Pré-Escolar , Progressão da Doença , Teste de Esforço , Seguimentos , Humanos , Masculino , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/genética , Estudos Retrospectivos , Esteroides/uso terapêuticoRESUMO
We have designed a multiplex ligation-dependent probe amplification (MLPA) assay to simultaneously screen all 79 DMD gene exons for deletions and duplications in Duchenne and Becker muscular dystrophy (DMD/BMD) patients. We validated the assay by screening 123 unrelated patients from Serbia and Montenegro already screened using multiplex PCR. MLPA screening confirmed the presence of all previously detected deletions. In addition, we detected seven new deletions, nine duplications, one point mutation, and we were able to precisely determine the extent of all rearrangements. To facilitate MLPA-based screening in laboratories lacking specific equipment, we designed the assay such that it can also be performed using agarose gel analysis and ethidium bromide staining. The MLPA assay as described provides a simple and cheap method for deletion and duplication screening in DMD/BMD patients. The assay outperforms the Beggs and Chamberlain multiplex-PCR test, and should be considered as the method of choice for an initial DNA analysis of DMD/BMD patients.
Assuntos
Deleção de Genes , Duplicação Gênica , Testes Genéticos/métodos , Distrofia Muscular de Duchenne/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Humanos , Distrofia Muscular de Duchenne/classificação , Reação em Cadeia da Polimerase , IugosláviaRESUMO
AIMS: Muscle biopsy is an important diagnostic modality and screening test for the diagnosis of dystrophinopathies. Sometimes muscle biopsies are needed for the diagnosis when genetic tests are inconclusive and are also useful for immunoblotting assay of the dystrophin protein. However, the procedure is painful, requires anesthesia and sometimes needs to be repeated. This study was undertaken to elucidate the role of skin biopsy in the diagnosis of dystrophinopathies and to validate if it can be utilized as a useful adjunct/replacement for the muscle biopsy. METHODS: Paired skin and muscle biopsies were studied from 39 patients with Duchenne muscular dystrophy (DMD), 4 patients with Becker's muscular dystrophy (BMD) and 37 controls. Immunostaining for dystrophin and utrophin was done on frozen sections of the test group and controls and their staining pattern in skin biopsies was compared with corresponding muscle biopsies. RESULTS: Immunostaining for dystrophin was negative in the skin biopsies of all patients (39/39, 100%) with DMD and was only weakly expressed in skin of BMD patients (4/4, 100%). Dystrophin was strongly expressed on arrector pili muscle cells of all control patients (94.6%) except two cases in whom it was weakly expressed. Utrophin was expressed on the arrector pili muscle cells of DMD patients (39/39, 100%) as well as controls (30/37, 81.1%). CONCLUSION: Our study suggests that skin biopsy is very useful for the diagnosis of dystrophinopathies and their differentiation from other muscle diseases. It has high degrees of sensitivity, specificity, and positive and negative predictive values. It can be a useful adjunct/replacement for the muscle biopsy especially when repeated biopsies are required for monitoring therapy or in patients with advanced DMD where extreme fibrosis, adipose tissue infiltration and inflammation make interpretation of the muscle biopsy difficult. Skin biopsy is a simple, cost effective, less invasive and less traumatic diagnostic procedure when compared with muscle biopsy. This is even more pertinent because patients with muscular dystrophies have a higher risk for any form of general anesthesia. A smaller scar and fewer chances of infection at the site of biopsy are other additional advantages of skin biopsy over muscle biopsy.