ABSTRACT
A Distrofia Muscular de Duchenne (DMD) é uma doença neuromuscular progressiva recessiva causada por mutações genéticas ligadas ao cromossomo X. Além do enfraquecimento muscular progressivo, a condição é associada a alterações neuropsicológicas. O objetivo deste estudo foi realizar uma revisão sistematizada da temática, para investigar os aspectos cognitivos e comportamentais associados à DMD pela literatura, nos últimos dez anos (2011-2021). Realizou-se uma revisão integrativa da literatura, com o propósito de sintetizar e analisar o conhecimento sobre o tema no campo científico, sendo efetuada busca nas bases de dados e motores de busca Science Direct, SciELO, PubMed e BVS. Após consideração dos critérios de inclusão e exclusão, foram selecionados 29 artigos para análise. Os resultados endossaram que alterações cognitivas e do neurodesenvolvimento, bem como de problemas comportamentais parecem ser mais prováveis na DMD, em comparação com a população geral. Verificou-se escassez de estudos empíricos brasileiros e a necessidade de avaliar e intervir nos âmbitos neuropsicológico e psicossocial, de forma precoce, contínua e multidisciplinar, no intuito de atender às necessidades desse grupo.
Duchenne Muscular Dystrophy (DMD) is a recessive progressive neuromuscular disease caused by X-linked genetic mutations. In addition to progressive muscle weakness, the condition is associated with neuropsychological alterations. The aim of this study was to perform a systematic review about the theme, to investigate the cognitive and behavioral aspects associated with DMD in the literature, over the last ten years (2011-2021). An integrative literature review was carried out, with the purpose of synthesizing and analyzing the knowledge on the subject in the scientific field, with a search in the databases and search engines Science Direct, SciELO, PubMed and BVS. After considering the inclusion and exclusion criteria, 29 articles were selected for analysis. The results endorsed that cognitive and neurodevelopmental alterations and behavioral problems seem to be more likely in DMD, when compared to the general population. There was a lack of brazilian empirical studies and the need to assess and intervene in the neuropsychological and psychosocial spheres was observed, in an early, continuous and multidisciplinary way, in order to meet the needs of this group.
La distrofia muscular de Duchenne (DMD) es una enfermedad neuromuscular progresiva recesiva causada por mutaciones genéticas ligadas al cromosoma X. Además de la debilidad muscular progresiva, la afección se asocia con cambios neuropsicológicos. El objetivo de este estudio fue realizar una revisión sistemática del tema, para investigar los aspectos cognitivos y conductuales asociados a la DMD en la literatura, en los últimos diez años (2011-2021). Se realizó una revisión integradora de la literatura, con el propósito de sintetizar y analizar el conocimiento sobre el tema en el campo científico, mediante una búsqueda en las bases de datos y motores de búsqueda Science Direct, SciELO, PubMed y BVS. Después de considerar los criterios de inclusión y exclusión, se seleccionaron 29 artículos para su análisis. Los resultados respaldaron que alteraciones cognitivas y del neurodesarrollo, así como problemas del comportamiento parecen ser más probables en la DMD en comparación con la población general. Se observó la escasez de estudios empíricos brasileños, así como la necesidad de evaluar e intervenir en los ámbitos neuropsicológico y psicosocial, de forma precoz, continua y multidisciplinar, para atender las necesidades de esta población.
Subject(s)
Cognition Disorders , Muscular Dystrophy, Duchenne , Mental Disorders , Learning DisabilitiesABSTRACT
Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.
Subject(s)
Humans , Abnormalities, Multiple , Retrospective Studies , Intellectual Disability/genetics , Bone Diseases, Developmental/complications , Tooth Abnormalities/complications , Facies , Muscular Dystrophy, Duchenne/complications , Muscular Atrophy, Spinal/complications , Carrier Proteins , Nuclear ProteinsABSTRACT
OBJECTIVE@#To explore the genetic basis for 7 families with gonadal mosaicism for Duchenne muscular dystrophy (DMD).@*METHODS@#For the 7 families presented at the CITIC Xiangya Reproductive and Genetic Hospital from September 2014 to March 2022, clinical data were collected. Preimplantation genetic testing for monogenic disorders (PGT-M) was carried out for the mother of the proband from family 6. Peripheral venous blood samples of the probands, their mothers and other patients from the families, amniotic fluid samples from families 1 ~ 4 and biopsied cells of embryos cultured in vitro from family 6 were collected for the extraction of genomic DNA. Multiplex ligation-dependent probe amplification (MLPA) was carried out for the DMD gene, and short tandem repeat (STR)/single nucleotide polymorphism (SNP)-based haplotypes were constructed for the probands, other patients, fetuses and embryos.@*RESULTS@#The results of MLPA showed that the probands and the fetuses/probands' brothers in families 1 ~ 4, 5, 7 had carried the same DMD gene variants, whilst the probands' mothers were all normal. The proband in family 6 carried the same DMD gene variant with only 1 embryo (9 in total) cultured in vitro, and the DMD gene of the proband's mother and the fetus obtained through the PGT-M were normal. STR-based haplotype analysis showed that the probands and the fetuses/probands' brothers in families 1 ~ 3 and 5 have inherited the same maternal X chromosome. SNP-based haplotype analysis showed that the proband from family 6 has inherited the same maternal X chromosome with only 1 embryo (9 in total) cultured in vitro. The fetuses in families 1 and 6 (via PGT-M) were both confirmed to be healthy by follow up, whilst the mothers from families 2 and 3 had chosen induced labor.@*CONCLUSION@#Haplotype analysis based on STR/SNP is an effective method for judging gonad mosaicism. Gonad mosaicisms should be suspected for women who have given births to children with DMD gene variants but with a normal peripheral blood genotype. Prenatal diagnosis and reproductive intervention may be adapted to reduce the births of further affected children in such families.
Subject(s)
Male , Pregnancy , Child , Humans , Female , Muscular Dystrophy, Duchenne/diagnosis , Dystrophin/genetics , Mosaicism , Exons , Prenatal Diagnosis/methods , NucleotidesABSTRACT
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.
Subject(s)
Humans , Male , Adult , Muscular Dystrophy, Duchenne/diagnosis , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/therapy , Cardiomyopathy, Dilated , Dystrophin/genetics , Muscular Dystrophy, Duchenne/classification , Muscular Dystrophy, Duchenne/physiopathology , Diagnosis, Differential , Heart FailureABSTRACT
INTRODUCTION: Since December 2019, the scientific community has been mobilized to contain the COVID-19 pandemic. Although individuals with Duchenne Muscular Dystrophy (DMD) have restrictive lung disease, risk of immunosuppression and associated cardiomyopathy, they are not considered to be a risk group for COVID-19. DMD is a neuromuscular, genetic and progressive disease, with early childhood development. In order to manage the disease, multidisciplinary follow-up is necessary to improve this patient's quality of life. OBJECTIVE: Identify the impact of the pandemic on the care of patients with DMD and its repercussions. METHOD: This is a cross-sectional, quantitative and descriptive study. The sample consisted of patients diagnosed with DMD aged between 4 and 18 years, followed up at the neuropediatrics service. Data collection was carried out by an interview with those responsible for the patient and evaluation of the medical records, using a questionnaire. Statistical analysis was descriptive using central tendency and dispersion measures. RESULTS: Among the 44 patients included, the median age was 12 years and the predominant type of gene mutation was deletion (56.8%). The median age of first symptoms was 4 years. Thirteen patients had contact with family members positive for COVID-19 and tested positive for the disease. Eleven received the vaccine against COVID-19. Medical followups suffered a great reduction in the pandemic period, as well as respiratory and motor physiotherapy. CONCLUSION: The pandemic interfered with multidisciplinary care for patients with DMD. As a chronic and degenerative disease, individuals with DMD require ongoing care, which was interrupted by the pandemic scenario.
INTRODUÇÃO: Desde dezembro de 2019, a comunidade científica está mobilizada para a contenção da pandemia pela COVID-19. Embora indivíduos portadores de Distrofia Muscular de Duchenne (DMD) apresentem doença pulmonar restritiva, risco de imunossupressão e cardiomiopatia associada, não são grupo de risco para a COVID-19. DMD é doença neuromuscular, genética e progressiva, de início na infância. Para manejo da doença, faz-se necessário acompanhamento multidisciplinar para melhora da qualidade de vida. OBJETIVO: Identificar o impacto da pandemia nos cuidados aos pacientes com DMD e suas repercussões. MÉTODOS: Trata-se de um estudo transversal, quantitativo e descritivo. A amostra foi composta por pacientes com diagnóstico de DMD com idade entre 4 e 18 anos acompanhados no serviço de neuropediatria. A coleta de dados foi realizada por entrevista com responsáveis e avaliação do prontuário, a partir de um questionário. A análise estatística foi descritiva com uso de medida de tendência central e dispersão. RESULTADOS: Dentre os 44 pacientes incluídos, a mediana de idade foi de 12 anos e o tipo de mutação gênica predominante a deleção (56,8%). A mediana de idade dos primeiros sintomas foi de 4 anos. Treze pacientes tiveram contato com familiares positivos para COVID-19 e testaram positivo para a doença. Onze receberam a vacina contra COVID-19. Os acompanhamentos médicos sofreram grande redução no período pandêmico, bem como a fisioterapia respiratória e motora. CONCLUSÃO: A pandemia interferiu nos atendimentos multidisciplinares aos pacientes com DMD. Como uma doença crônica e degenerativa, os indivíduos com DMD necessitam de cuidados contínuos, o que foi interrompido pelo cenário pandêmico.
Subject(s)
Humans , Child, Preschool , Child , Adolescent , Patient Care Team , Muscular Dystrophy, Duchenne/diagnosis , Muscular Dystrophy, Duchenne/therapy , Withholding Treatment , Pandemics , COVID-19/prevention & control , Cross-Sectional Studies , Surveys and QuestionnairesABSTRACT
Estudo de caracterização da força e da função muscular nas disferlinopatias para estabelecer biomarcadores de habilidades motoras com amostra de 40 pacientes, tendo sido avaliados força muscular (Medical Research Council - MRC), percentual de MRC, tempo de execução para deambular e escores nas Escalas de Vignos, Egen Klassifikation, Avaliação Funcional para Distrofia Muscular de Duchenne (FES-DMD) e North Star Ambulatory Assessment adaptada. Prevalência da disferlinopatia de 25,5% na amostra total de distrofias (1340), idade média de 36,5 anos, 52,5% do sexo masculino e 75% deambuladores. Músculos mais fracos: abdominal, glúteos, íliopsoas, isquiotibial, quadríceps femoral, tibial anterior e deltoide médio. Correlação forte entre MRC e tempo para deambular (r = 0,77) e, muito forte da MRC distal de membros inferiores com aNSAA (r = 0,90). Interação da MRC dos membros superiores e inferiores nos segmentos proximal e distal (p < 0,001), sendo mais evidente em membros superiores que inferiores. Taxa variável de progressão da doença com 60% dos pacientes moderadamente ou gravemente afetados, com mais de 12 anos de doença. Estudo mostra que padrão de fraqueza muscular dos brasileiros com disferlinopatia é proximal e distal dos MMII, com comprometimento associado da região proximal dos MMSS, além de elucidar as habilidades motoras em relação ao processo de locomoção e disfunções cardiorrespiratórias. (AU).
Subject(s)
Humans , Biomarkers , Disease Progression , Muscle Weakness , Muscular Dystrophy, Duchenne , Motor Skills , DysferlinABSTRACT
OBJECTIVE@#To explore the genetic basis of a Chinese pedigree affected with Becker muscular dystrophy (BMD) with myalgia as the main feature.@*METHODS@#Clinical data of the patients and results of auxiliary examinations were retrospectively analyzed. Multiplex ligation-dependent probe amplification and high-throughput sequencing were used to detect potential variants. Sanger sequencing was used to verify the results.@*RESULTS@#The clinical manifestations of the proband included myalgia and elevated serum creatine kinase, which is similar to another patient from the pedigree. Genetic testing revealed that the two patients both harbored hemizygous deletions of exons 10 to 29 of the DMD gene, for which the mother was a carrier. The same deletion was not found in his father. Based on the guidelines from American College of Medical Genetics and Genomics, the deletion was predicted to be pathogenic (PVS1+PM2+PP1).@*CONCLUSION@#Myalgia with elevated serum CK may be atypical clinical manifestations of BMD and may be associated with variants in the rod domain of the DMD gene. The deletion of exons 10 to 29 of the DMD gene probably underlay the BMD in this pedigree.
Subject(s)
Female , Humans , China , Dystrophin/genetics , Genetic Testing , Muscular Dystrophy, Duchenne/genetics , Myalgia/genetics , Pedigree , Retrospective StudiesABSTRACT
ABSTRACT Background: Analysis of autonomic modulation after postural change may inform the prognosis and guide treatment in different populations. However, this has been insufficiently explored among adolescents with Duchenne muscular dystrophy (DMD). Objective: To investigate autonomic modulation at rest and in response to an active sitting test (AST) among adolescents with DMD. Methods: Fifty-nine adolescents were included in the study and divided into two groups: 1) DMD group: adolescents diagnosed with DMD; 2) control group (CG): healthy adolescents. Participants' weight and height were assessed. Lower limb function, motor limitations and functional abilities of the participants in the DMD group were classified using the Vignos scale, Egen classification and motor function measurement, respectively. The following variables were assessed before, during and after AST: systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (f), oxygen saturation and heart rate (HR). To analyze the autonomic modulation, the HR was recorded beat-by-beat. Heart rate variability (HRV) indices were calculated in the time and frequency domains. Results: Differences in relation to groups were observed for all HRV indices, except LF/HF, oxygen saturation, HR and f (p < 0.05). Differences in relation to time and the interaction effect between group and time were observed for RMSSD, SD1, SD2, SD1/SD2, LFms2 and LFnu, HFun, SBP and DBP (p < 0.05). Differences in relation to time were also observed for the indice SDNN, FC and f (p < 0.05). Conclusions: Performing the AST promoted reduced autonomic modulation and increased SBP, DBP and HR in adolescents with DMD.
Resumo Antecedentes: A análise da modulação autonômica após mudanças posturais pode gerar informações prognósticas e orientar o tratamento em diferentes populações. Porém, isso não foi suficientemente explorado em adolescentes com DMD. Objetivo: Investigar a modulação autonômica em repouso e em resposta ao teste ativo sentado (TAS) em adolescentes com DMD. Métodos: 59 adolescentes foram incluídos no estudo e divididos em dois grupos: 1) Grupo DMD: adolescentes com diagnóstico de DMD; 2) Grupo controle: adolescentes saudáveis. O peso e a altura dos participantes foram avaliados. No grupo DMD, a funcionalidade de membros superiores, limitações motoras, e habilidades funcionais foram classificadas pela escala de Vignos, Egen Klassification, e motor function measure respectivamente. Pressão arterial sistólica (PAS), pressão arterial diastólica (PAD), frequência respiratória (f), saturação de oxigênio, e frequência cardíaca (FC) foram avaliadas em repouso, durante e após o TAS. Para analisar a modulação autonômica, a FC foi registrada batimento a batimento. Os índices de variabilidade da frequência cardíaca (VFC) foram calculados nos domínios do tempo e da frequência. Resultados: Diferenças entre os grupos foram observadas para todos os índices da VFC, exceto LF/HF, saturação de oxigênio, FC e f (p<0,05). Diferenças em relação ao tempo e interação entre grupo e tempo foram observadas para RMSSD, SD1, SD2, SD1/SD2, LFms2, LFun, HFnu, SBP e DBP (p<0,05). Diferenças em relação ao tempo foram também observadas para o índice SDNN, FC e f (p<0,05). Conclusões: A realização do TAS promoveu redução da modulação autonômica e aumento da PAS, PAD e FC em adolescentes com DMD.
Subject(s)
Humans , Adolescent , Muscular Dystrophy, Duchenne , Autonomic Nervous System , Blood Pressure , Cross-Sectional Studies , Heart RateABSTRACT
Se presenta el caso clínico de un adolescente de 18 años de edad, atendido en el Policlínico Docente Armando García Aspurú de Santiago de Cuba por presentar antecedentes de retardo en el desarrollo psicomotor, marcha anadeante, caídas frecuentes, signo de Gowers positivo, fuerza muscular proximal disminuida en miembros superiores e inferiores, pseudohipertrofia de los gemelos, atrofia de cuádriceps pectoral y escapular. Los signos y síntomas clínicos permitieron diagnosticar una distrofia muscular de Duchenne. Como no pudo realizarse el tratamiento rehabilitador necesario, se produjo un deterioro músculo - esquelético progresivo y severo del paciente.
The case report of an 18 years adolescent is presented. He was assisted at Armando García Aspurú Teaching Polyclinic in Santiago de Cuba due to a history of psychomotor development retardation, wandering march, frequent falls, positive Gowers sign, diminished proximal muscular force in upper and lower limbs, twins pseudohypertrophy, atrophy of pectoralis and scapular quadriceps. The clinical signs and symptoms allowed to diagnose a Duchenne muscular dystrophy. As the necessary rehabilitative treatment could not be carried out, a progressive and severe musculoskeletal deterioration of the patient took place.
Subject(s)
Muscular Dystrophy, Duchenne/diagnosis , Muscular Dystrophy, Duchenne/rehabilitation , Developmental Disabilities/diagnosis , Adolescent , Muscles/pathologyABSTRACT
OBJETIVO: Pesquisar as recomendações nutricionais para pacientes com Distrofia Muscular de Duchenne (DMD). MÉTODO: Trata- se de uma revisão integrativa da literatura, através de levantamento bibliográfico nas bases cientificas PubMed e Scielo, foram utilizadas as palavras chaves: Distrofia Muscular de Duchenne em combinação com os termos Nutrição, Nutrientes, Nutracêuticos, Vitaminas e Antioxidantes. Foi realizada a busca dos artigos publicados nos últimos 10 anos. RESULTADOS: Foram selecionados 102 artigos, dos quais após análise dos critérios de exclusão e inclusão, resultaram em 31 artigos referentes a 31,62% da amostra inicial que foram utilizados para a produção dessa revisão. CONCLUSÃO: O acompanhamento nutricional do paciente com DMD é fundamental, de forma a garantir a manutenção do estado nutricional, além de contribuir de forma significativa para a desaceleração dos sintomas da doença e melhora da qualidade de vida.
OBJECTIVE: To search for nutritional recommendations for patients with Duchenne Muscular Dystrophy (DMD). METHOD: It is an integrative review of the literature, through a bibliographic survey on the scientific bases PubMed and Scielo, the keywords used were Duchenne Muscular Dystrophy in combination with the terms Nutrition, Nutrients, Nutraceuticals, Vitamins and Antioxidants. The search was based on articles published in the last 10 years. RESULTS: A total of 102 articles were selected, of which, after analyzing the exclusion and inclusion criteria, resulted in 32 articles referring to 32.64% of the initial sample that were used to produce this review. CONCLUSION: Nutritional monitoring of patients with DMD is essential, in order to guarantee the maintenance of nutritional status, in addition to contributing significantly to the deceleration of the symptoms of the disease and improving the quality of life.
Subject(s)
Humans , Male , Child, Preschool , Child , Adolescent , Vitamins/administration & dosage , Muscular Dystrophy, Duchenne/diagnosis , Muscular Dystrophy, Duchenne/diet therapy , Nutrition Therapy/methods , Recommended Dietary Allowances , Nutritional Status , AntioxidantsABSTRACT
Duchenne muscular dystrophy (DMD) is one of the most common neuromuscular diseases. Its evolution with well-defined stages related to motor and functional alterations, allows easily establishing relationships with respiratory function through a simple laboratory assessment including vital capacity (VC) measurements as well as peak cough flows. Without any treatment with respiratory rehabilitation, the main cause of morbidity and mortality is ventilatory failure, secondary to respiratory pump muscles weakness and inefficient cough. The VC plateau is reached during the non-ambulatory stages, generally after 13 years old. Respiratory rehabilitation protocols, including air stacking techniques, manual and mechanical assisted coughing and non-invasive ventilatory support, can effectively addressed the VC decline as well as the decrease in peak cough flows, despite advancing to stages with practically non-existent lung capacity. Non-invasive ventilatory support may be applied after 19 years old, initially at night and then extending it during the day. In this way, survival is prolonged, with good quality of life, avoiding ventilatory failure, endotracheal intubation and tracheostomy. This article proposes staggered interventions for respiratory rehabilitation based on the functional stages expected in the patient with DMD who has lost ambulation.
La distrofia muscular de Duchenne (DMD) es una de las enfermedades neuromusculares más frecuentes. Su curso evolutivo con etapas de declinación en la funcionalidad motora bien definidas, permite fácilmente establecer relaciones con la función respiratoria a través de un laboratorio de evaluación sencilla, básicamente de la capacidad vital (CV) y la capacidad tusígena. Sin intervenciones en rehabilitación respiratoria, la principal causa de morbimortalidad es la insuficiencia ventilatoria secundaria a debilidad de músculos de la bomba respiratoria e ineficiencia de la tos. En las etapas no ambulantes, se alcanza la meseta de la CV, generalmente después de los 13 años, su declinación junto con la disminución de la capacidad tusígena puede ser enfrentada efectivamente con la utilización de protocolos de rehabilitación respiratoria. Estos deben considerar la restitución de la CV con técnicas de insuflación activa o apilamiento de aire, tos asistida manual y mecánica, más soporte ventilatorio no invasivo, inicialmente nocturno después de los 19 años y luego diurno, pese a avanzar a etapas con capacidad pulmonar prácticamente inexistente. De esta manera, se prolonga la sobrevida, con buena calidad de vida, evitando el fallo ventilatorio, eventos de intubación endotraqueal y traqueostomía. Este artículo, hace propuestas escalonadas de intervención en rehabilitación respiratoria basadas en las etapas funcionales esperables en el paciente con DMD que ha perdido la capacidad de marcha.
Subject(s)
Humans , Respiratory Therapy/methods , Muscular Dystrophy, Duchenne/rehabilitation , Scoliosis/rehabilitation , Vital Capacity , Noninvasive VentilationABSTRACT
Objetivo: Relacionar a capacidade funcional de pacientes com Distrofia Muscular de Duchenne com a sobrecarga dos seus cuidadores familiares. Métodos: Estudo transversal com amostra composta por 35 pacientes e seus cuidadores familiares, de um centro de reabilitação de Goiânia-GO. Foram utilizados para avaliação da capacidade funcional a Escala de Vignos, Medida da Função Motora, Índice de Barthel e Escala Egen Klassification e para avaliação da sobrecarga o Burden Interview. Resultados: Os cuidadores estavam com sobrecarga moderada, com média de 23,6 (±10,3). A pontuação média dos instrumentos demonstrou que os pacientes estavam em fase avançada de estadiamento da doença e prejuízo da capacidade funcional. Não foi encontrada relação significativa entre a sobrecarga dos cuidadores e a capacidade funcional dos pacientes. Conclusão: O cuidador está diretamente ligado à função de zelar do paciente, portanto a equipe multiprofissional precisa se atentar também à saúde mental deste, oferecendo suporte para intervenções especializadas
Objective: To relate a functional capacity of patients with Duchenne muscular dystrophy to the burden of their family caregivers. Methods: A cross-sectional study with 35 patients and their family caregivers from a rehabilitation center in Goiânia-GO. Were used for the functional evaluation of the Vignos Scale, Motor Function Measure Scale, Barthel Index, Egen Klassification Scale and for burden evaluation the Burden Interview. Results: The caregivers had moderate burden, with a mean of 23,6 (± 10,3). Regarding the patients, the average score of the instruments showed that they were in an advanced stage of disease staging and impairment of functional capacity. No significant relationship was found between the caregiver burden and the patient's functional capacity. Conclusion: The caregiver is directly connected to the care function of the patient, so the multiprofessional team needs to pay attention to their mental health, offering support for specialized interventions
Objetivo: Relacionar la capacidad funcional de pacientes con Distrofia Muscular de Duchenne con la sobrecarga de sus cuidadores familiares. Métodos: Estudio transversal con muestra compuesta por 35 pacientes y sus cuidadores familiares, de un centro de rehabilitación de Goiânia-GO. Se utilizaron para la evaluación de la capacidad funcional la Escala de Vignos, Medida de la Función Motora, Índice de Barthel y Escala Egen Klassification y para evaluación de la sobrecarga el Burden Interview. Resultados: La sobrecarga de los cuidadores fue considerada moderada, con promedio de 23,6 (± 10,3). En cuanto a los pacientes, la puntuación media de los instrumentos demostró que estaban en fase avanzada de estadificación de la enfermedad y perjuicio de la capacidad funcional. No se encontró una relación significativa entre la sobrecarga de los cuidadores y la capacidad funcional de los pacientes. Conclusión: El cuidador está directamente ligado a la función de velar del paciente, por lo tanto el equipo multiprofesional necesita atenderse también a la salud mental de éste, ofreciendo soporte para intervenciones especializadas
Subject(s)
Humans , Male , Female , Patient Care Team , Caregivers/psychology , Muscular Dystrophy, Duchenne , Burnout, PsychologicalABSTRACT
Abstract Duchenne muscular dystrophy (DMD) is a chronic disease that primarily affects males and is characterized by progressive physical impairment and, eventually, death. This qualitative study aimed to explore and understand the experience of diagnosis and disease in young people with DMD living in Bogotá, Colombia. After securing approval from the Research Ethics Committee (CEI-ABN026-000311), nine individuals took part of a semi-structured interview, and their narratives were analyzed using thematic analysis. The main topics developed throughout the narratives were: negative representation of the disease; fear; difficulty expressing emotions; the patient-doctor relationship; the wheelchair; the caregivers and coping strategies. We conclude that young people affected by DMD face several challenging experiences that underscore the need for better, more respectful, and compassionate interactions with healthcare providers. Also, their experiences are indicative of a socio-cultural context that needs to become more responsive and compassionate towards young people and disability.
Resumo A distrofia muscular de Duchenne (DMD) é uma doença crônica que afeta principalmente os homens, caracterizada pelo deterioro físico progressivo e por conduzir à morte. Este estudo qualitativo teve como objetivo a exploração e a compreensão da experiência do diagnóstico e da doença em jovens com DMD residentes em Bogotá, Colômbia. Após a aprovação do Comitê de Ética em Pesquisa (CEI-ABN026-000311), nove participantes participaram numa entrevista semiestruturada e as suas narrativas foram analisadas através da análise temática. Os principais temas abordados foram: a representação negativa da doença; o medo; a dificuldade em expressar emoções; a relação paciente-médico; a cadeira de rodas; os cuidadores e as estratégias de resiliência. Concluímos que os jovens afetados pela DMD enfrentam experiências desafiantes que evidenciam a necessidade de interações melhores, mais respeitosas e compassivas com os profissionais de saúde. Ao mesmo tempo, as suas experiências são indicativas de um contexto sociocultural que precisa de se tornar mais recetivo e compassivo para com os jovens e as deficiências.
Résumé La Dystrophie Musculaire de Duchenne (DMD) est une maladie chronique qui touche principalement les hommes et se caractérise par détérioration physique progressive et, éventuellement, la mort. Cette rechérche qualitative a explorer l'expérience du diagnostic et de la maladie chez les jeunes atteints de DMD à Bogotá, Colombie. Cette rechérche a été évaluée et approuvée par un comité d'éthique de la recherche (CEI-ABN026-000311). Neuf jeunes ont participé à un entretien semi-structuré et leurs récits ont été analysés à l'aide d'une analyse thématique. Les principaux thèmes développés dans les récits étaient: la représentation négative de la maladie; peur; difficulté à exprimer ses émotions; la relation médecin-patient; le fauteuil roulant; soignants et stratégies d'adaptation. Nous concluons que les jeunes touchés par la DMD vivent de multiples expériences difficiles qui mettent en évidence la nécessité d'interactions plus respectueuses et plus compatissantes avec les prestataires de services de santé. En même temps, leurs expériences montrent un contexte socioculturel qui doit être plus sensible et compatissant envers les enfants et les jeunes handicapés.
Resumen La distrofia muscular de Duchenne (DMD) es una enfermedad crónica que afecta principalmente a hombres y se caracteriza por deterioro físico progresivo y, eventualmente, la muerte. Este estudio cualitativo buscó explorar y comprender la experiencia del diagnóstico y la enfermedad en jóvenes con DMD en la ciudad de Bogotá, Colombia. Tras recibir autorización del Comité de Ética en Investigación (CEI-ABN026-000311), nueve participantes colaboraron con una entrevista semiestructurada y sus narrativas fueron analizadas usando análisis temático. Los principales temas desarrollados en las narrativas fueron: representación negativa de la enfermedad; miedo; dificultad expresando emociones; la relación médico-paciente; la silla de ruedas; los cuidadores y las estrategias de afrontamiento. Concluimos que los jóvenes afectados por la DMD enfrentan múltiples experiencias retadoras que hacen evidente la necesidad de interacciones más respetuosas y compasivas con los proveedores de servicios de salud. Al mismo tiempo, sus experiencias muestran un contexto sociocultural que necesita ser más sensible y compasivo con los niños y jóvenes en situación de discapacidad.
Subject(s)
Humans , Male , Child , Adolescent , Adult , Muscular Dystrophy, Duchenne/psychology , Colombia , Life Change EventsABSTRACT
ABSTRACT Objective: To verify the interval of responsiveness to the scales Segmental Assessment of Trunk Control (SATCo-BR), Performance of Upper Limbs (PUL), and Jebsen Taylor Test (JTT) in patients with Duchenne Muscular Dystrophy (DMD). Methods: We assessed patients with DMD aged 6 to 19 years old and with mini-mental (MMSE) score above 10 points. The assessments were performed individually, in a single session. The upper limb function was performed by PUL and JTT, and trunk control by SATCo-BR. Assessments were repeated six and 12 months after the initial assessment. The repeated-measures analysis of variance model and Bonferroni's multiple comparison method were employed as post hoc analysis; when the ANOVA assumptions were not met, the Friedman test was applied. Results: The sample consisted of 28 patients evaluated in three moments (initial, and six and 12 months after the beginning). There was a time effect for the Upper Limb function performance in the total JTT, and for the subtests, except for subtests 1 and 6, which did not show a difference between the different moments. There was also a time effect for the score of total PUL, proximal PUL, intermediate PUL, and distal PUL. In the SATCo-BR, this effect was observed between the initial and 6 months, and between the initial and 12 months. Conclusions: The JTT, PUL, and SATCo-BR scales can detect changes over time, and they showed responsiveness to detect the evolution of the disease in the 6-month interval.
RESUMO Objetivo: Verificar o intervalo de tempo para a responsividade das escalas Segmental Assessment of Trunk Control (SATCo-BR), Performance of Upper Limb (PUL) e o Teste de Função Manual de Jebsen Taylor (TJT) em pacientes com distrofia muscular de Duchenne (DMD). Métodos: Foram avaliados pacientes com DMD nas idades entre 6 e 19 anos, e com escore do Mini Exame do Estado Mental (MEEM) a partir de 10 pontos. As avaliações foram realizadas individualmente, em uma única sessão: a função de membro superior (MS) ocorreu pela PUL e TJT; e da do controle de tronco, pela SATCo-BR. As avaliações foram repetidas após seis e 12 meses da avaliação inicial. Foi empregado o modelo de análise de variância com medidas repetidas e o método de comparações múltiplas de Bonferroni, como análise post hoc; quando os pressupostos da ANOVA não foram atendidos, foi aplicado o teste de Friedman. Resultados: A amostra foi composta por 28 pacientes avaliados em três momentos (inicial, após seis meses e após 12 meses). Houve efeito do tempo no desempenho da função Membro Superior no TJT total e nos subtestes, exceto nos subtestes 1 e 6, que não apresentaram diferença nas avaliações entre os diferentes momentos. Houve efeito do tempo para o escore da PUL total, PUL proximal, PUL intermediário e PUL distal. No SATCo-BR, esse efeito foi entre o inicial e após seis meses, e entre o inicial e após 12 meses. Conclusões: As escalas TJT, PUL e SATCo-BR são capazes de detectar alterações ao longo do tempo, e apresentam responsividade para detectar a evolução da doença em intervalo de 6 meses.
Subject(s)
Humans , Male , Child , Adolescent , Young Adult , Weights and Measures/standards , Muscular Dystrophy, Duchenne/physiopathology , Upper Extremity/physiopathology , Postural Balance/physiology , Torso/physiopathology , Time Factors , Anthropometry/methods , Longitudinal Studies , Disease Progression , Muscular Dystrophy, Duchenne/diagnosis , Muscular Dystrophy, Duchenne/epidemiology , Mental Status and Dementia Tests/statistics & numerical data , Physical Functional PerformanceABSTRACT
Basal cell nevus syndrome (BCNS), also known as Gorlin-Goltz syndrome, is a rare autosomal dominant genetic disease. It is thought to be caused by a mutation in the PTCH1 gene, and its incidence is 1/57 000 to 1/256 000. The case of a 7-year-old patient with BCNS and Duchenne muscular dystrophy was reported in this paper.
Subject(s)
Child , Humans , Basal Cell Nevus Syndrome/diagnosis , Muscular Dystrophy, Duchenne , MutationABSTRACT
OBJECTIVE@#To identify the etiology of a patient with severe symptoms of DMD and to trace its pathogenic gene, so as to provide a basis for genetic counseling and clinical intervention.@*METHODS@#Multiple ligation-dependent probe amplification (MLPA) technique was used to analyze exon deletion/repetitive variant of DMD gene, and further analysis was performed by chromosome G-banding, fluorescence in situ hybridization (FISH) and SNP array analysis.@*RESULTS@#The MLPA results of the proband showed that the exon 1-79 of DMD gene were deleted, the G-banding karyotype of blood sample was 46, XY, and the deletion of the short arm of X chromosome was found by FISH. SNP array results showed that 5.8Mb (29 628 158-35 434 714) deletion occurred in the Xp21.2p21.1 region of X chromosome, and the patient was diagnosed as the contiguous deletion syndrome involving the genes of IL1RAPL, MAGEB1-4, ROB, CXorf2, GM, AP3K7IP, FTHL1, DMD, FAM47A, TMEM47, and FAM47B.@*CONCLUSION@#The exact pathogenic site of this family is the deletion of 5.8 Mb (29 628 158-35 434 714) in the Xp21.2p21.1 region of X chromosome, which can be used for prenatal diagnosis. High resolution SNP array technique plays an important role in detecting potential chromosome abnormalities in patients.
Subject(s)
Female , Humans , Pregnancy , Dystrophin/genetics , Exons , Gene Deletion , In Situ Hybridization, Fluorescence , Muscular Dystrophy, Duchenne/genetics , Prenatal DiagnosisABSTRACT
OBJECTIVE@#To establish a screening model for females of reproductive age carrying Duchenne muscular dystrophy (DMD) variants based on a current community health examination platform.@*METHODS@#A total of 61 870 participants were recruited between October 2017 and October 2019. Serum creatine kinase (CK) was measured with a Roche Cobasc 701/702 using an enzymatic rate method. Genetic testing was offered to those with a CK level of ≥ 200 U/L. For carriers of DMD variants, genetic counseling and follow up were provided.@*RESULTS@#For the 61 870 females participating in the program, 1078 were found with raised serum CK (≥ 200 U/L), of which 618 (57.33%) accepted CK re-measurement after at least a two-week interval. One hundred and twenty cases were found with sustained serum CK elevation, of which 6 were confirmed to be definite DMD carriers regardless of family history. Genetic testing was provided to 33 females with a family history for DMD, and 13 were determined as definite carriers. An affected fetus was detected by prenatal diagnosis. After genetic counseling, the parents had opted induced abortion.@*CONCLUSION@#Large-scale DMD carrier screening through a three-step approach based on the current community health examination platform is both feasible and cost effective.
Subject(s)
Female , Humans , Pregnancy , Genetic Carrier Screening , Genetic Counseling , Genetic Testing , Muscular Dystrophy, Duchenne/genetics , Prenatal DiagnosisABSTRACT
OBJECTIVE@#To establish a newborn screening system for Duchenne muscular dystrophy (DMD) through assessment of MM isoenzyme of creatine kinase (CK-MM) activity.@*METHODS@#The CK-MM level was detected using dry blood spot filter paper from 10 252 male newborns. The results were grouped based on their gestational age, sampling time and intervals between the experiments. The threshold value for CK-MM necessitating genetic testing was determined. Next-generation sequencing (NGS) was carried out for those with a CK-MM value over the threshold, and the result was verified by multiplex ligation-dependent probe amplification (MLPA).@*RESULTS@#Based on the result of non-parametric rank sum test, the median CK-MM concentration has increased with the gestational age, and was inversely correlated with the age of the newborns among unaffected specimens. CK-MM on dry blood spot filter paper can be stable for 14 days at 2-8℃. Statistical analysis of CK-MM value of the 10 252 neonates suggested that the threshold may be set as 700 ng/mL. Exonic deletions were found in 2 confirmed cases, whose CK-MM level was greater than 2000 ng/mL.@*CONCLUSION@#Detection of CK-MM in dry blood spot filter paper has provided an effective method for newborn screening of DMD. This simple and inexpensive method can be used for large-scale screening, which is of great value to the early intervention and treatment of the disease.
Subject(s)
Humans , Infant, Newborn , Male , Dystrophin/genetics , Exons , Multiplex Polymerase Chain Reaction , Muscular Dystrophy, Duchenne/genetics , Neonatal ScreeningABSTRACT
OBJECTIVE@#To summarize the result of genetic testing and therapeutic prospect of 2042 unrelated Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD) from a single center from 2005 to 2019.@*METHODS@#Peripheral blood samples of the pedigrees were collected for the detection of DMD gene variants with combined multiple ligation-dependent probe amplification (MLPA), next generation sequencing (NGS) and Sanger sequencing.@*RESULTS@#DMD and BMD have respectively accounted for 78.60% and 21.40% of the pedigrees, which included 33 female probands. Variants of the DMD gene were detected in 1986 pedigrees (97.26%). Large deletions, duplications and small-scale mutations have respectively accounted for 71.85%, 8.76% and 19.39%. Common deletions and duplications have included deletion of exons 45-50 and duplications of exon 2, while no hot spot was found with small-scale mutations. For 1595 pedigrees affected with DMD, 935 (58.62%) were hereditary and 660 (41.38%) were de novo in origin. 34.28% (700/2042) of the patients had symptoms which could be relieved by gene therapy.@*CONCLUSION@#This has been the largest single-center study of DMD pedigrees, which has attained definite diagnosis in 97.26% of the patients. The results have enabled genetic counseling and prenatal diagnosis for the affected families upon their subsequent pregnancies, enriched the spectrum of DMD gene variants, as well as facilitated study of the mechanism of DMD gene mutations and exploration of clinical treatment.
Subject(s)
Female , Humans , Pregnancy , China , Dystrophin/genetics , Exons/genetics , Gene Deletion , Genetic Testing , Muscular Dystrophy, Duchenne/therapy , Mutation , PedigreeABSTRACT
The Golden Retriever muscular dystrophy (GRMD) is one of the best models of Duchenne muscular dystrophy (DMD), with similar genotypic and phenotypic manifestations. Progressive proliferation of connective tissue in the endomysium of the muscle fibers occurs in parallel with the clinical course of the disease in GRMD animals. Previous studies suggest a relationship between mast cells and the deposition of fibrous tissue due to the release of mediators that recruit fibroblasts. The aim of this study was to evaluate the presence of mast cells and their relationship with muscle injury and fibrosis in GRMD dogs of different ages. Samples of muscle groups from six GRMD and four control dogs, aged 2 to 8 months, were collected and analyzed. The samples were processed and stained with HE, toluidine blue, and Azan trichrome. Our results showed that there was a significant increase in infiltration of mast cells in all muscle groups of GRMD dogs compared to the control group. The average number of mast cells, as well as the deposition of fibrous tissue, decreased with age in GRMD dogs. In the control group, all muscle types showed a significant increase in the amount of collagenous tissue. This suggests increased mast cell degranulation occurred in younger GRMD dogs, resulting in increased interstitial space and fibrous tissue in muscle, which then gradually decreased over time as the dogs aged. However, further studies are needed to clarify the role of mast cells in the pathogenesis of fibrosis.(AU)
O cão Golden Retriever distrófico (Golden Retriever muscular dystrophy - GRMD) é um dos melhores modelos da distrofia muscular de Duchenne (DMD), com manifestações genotípicas e fenotípicas similares. A proliferação progressiva de tecido conjuntivo no endomísio das fibras musculares ocorre paralelamente ao curso clínico da doença em animais GRMD. Estudos anteriores sugerem uma relação entre os mastócitos e a deposição de tecido fibroso devido à liberação de mediadores que recrutam fibroblastos. O objetivo deste estudo foi avaliar a presença de mastócitos e sua relação com a lesão muscular e fibrose em cães GRMD de diferentes idades. Amostras de grupos musculares de seis GRMD e quatro controles, com idade entre 2 a 8 meses, foram coletadas e analisadas. As amostras foram processadas e coradas com HE, azul de toluidina e tricrômico de Azan. Nossos resultados mostraram que houve um aumento significativo na infiltração de mastócitos em todos os grupos musculares de cães GRMD em comparação com o grupo controle. O número médio de mastócitos, assim como a deposição de tecido fibroso, diminuiu com a idade em cães GRMD. No grupo controle, todos os tipos musculares mostraram um aumento significativo na quantidade de tecido colágeno. Isto sugere o aumento da degranulação de mastócitos em cães GRMD mais jovens, resultando em aumento do espaço intersticial e tecido fibroso no músculo, que então gradualmente diminuiu com o tempo à medida que os cães envelheceram. No entanto, mais estudos são necessários para esclarecer o papel dos mastócitos na patogênese da fibrose.(AU)