RESUMO
Emery-Dreifuss muscular dystrophy is a rare hereditary neuromuscular disease. Its manifestations begin primarily in childhood. The most frequent manifestations are progressive muscle weakness, atrophy that usually begins in the scapula-vertebral region, extending later to the pelvic girdle, and spinal stiffness. Patients can also manifest cardiac involvement as palpitations, syncope, exercise intolerance, congestive heart failure, and variable heart rhythm disturbances. 1 - 3 The presence and severity of these manifestations can vary according to the individual and the disease's subtypes. 2 Cardiac involvement is the most worrisome feature of this disease, and there are some reports of the need for heart transplantation in this dystrophy. 4.
A distrofia muscular de Emery-Dreifuss é uma doença neuromuscular hereditária rara. Suas manifestações começam principalmente na infância. As manifestações mais frequentes são fraqueza muscular progressiva, atrofia que geralmente se inicia na região escápulo-vertebral, estendendo-se posteriormente para a cintura pélvica e rigidez da coluna vertebral. Os pacientes também podem manifestar envolvimento cardíaco como palpitações, síncope, intolerância ao exercício, insuficiência cardíaca congestiva e distúrbios variáveis do ritmo cardíaco. 1 - 3 A presença e a gravidade dessas manifestações podem variar de acordo com o indivíduo e os subtipos da doença. 2 O envolvimento cardíaco é a característica mais preocupante desta doença, havendo alguns relatos da necessidade de transplante cardíaco nesta distrofia. 4.
Assuntos
Reabilitação Cardíaca , Insuficiência Cardíaca , Transplante de Coração , Distrofia Muscular de Emery-Dreifuss , Humanos , Arritmias CardíacasRESUMO
Abstract Emery-Dreifuss Muscular Dystrophy is a very rare type of muscular dystrophy, associated with contractures, atrophy, and muscle weakness, besides cardiomyopathy with severe arrhythmias. Published studies focusing on this disorder are scarce. We describe the anesthetic management of a male patient with Emery-Dreifuss Muscular Dystrophy, to be submitted to umbilical and inguinal hernioplasty and hydrocele repair under epidural anesthesia. The anesthesia approach enabled us to circumvent the patient's susceptibility to malignant hyperthermia and his potentially difficult airway, in addition to maintaining hemodynamic stability. The day after surgery the patient resumed walking, and two days later he was discharged from the hospital.
Assuntos
Humanos , Masculino , Distrofia Muscular de Emery-Dreifuss/complicações , Distrofia Muscular de Emery-Dreifuss/patologia , Anestesia Epidural , Anestésicos , Hipertermia MalignaRESUMO
Emery-Dreifuss Muscular Dystrophy is a very rare type of muscular dystrophy, associated with contractures, atrophy, and muscle weakness, besides cardiomyopathy with severe arrhythmias. Published studies focusing on this disorder are scarce. We describe the anesthetic management of a male patient with Emery-Dreifuss Muscular Dystrophy, to be submitted to umbilical and inguinal hernioplasty and hydrocele repair under epidural anesthesia. The anesthesia approach enabled us to circumvent the patient...s susceptibility to malignant hyperthermia and his potentially difficult airway, in addition to maintaining hemodynamic stability. The day after surgery the patient resumed walking, and two days later he was discharged from the hospital.
Assuntos
Anestesia Epidural , Anestésicos , Hipertermia Maligna , Distrofia Muscular de Emery-Dreifuss , Humanos , Masculino , Distrofia Muscular de Emery-Dreifuss/complicações , Distrofia Muscular de Emery-Dreifuss/patologiaRESUMO
ß-dystroglycan (ß-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of ß-DG, we characterized the interaction between ß-DG and emerin at the molecular level. Emerin is a major NE protein that regulates multiple nuclear processes and whose deficiency results in Emery-Dreifuss muscular dystrophy (EDMD). Using truncated variants of ß-DG and emerin, via a series of in vitro and in vivo binding experiments and a tailored computational analysis, we determined that the ß-DG-emerin interaction is mediated at least in part by their respective transmembrane domains (TM). Using surface plasmon resonance assays we showed that emerin binds to ß-DG with high affinity (KD in the nanomolar range). Remarkably, the analysis of cells in which DG was knocked out demonstrated that loss of ß-DG resulted in a decreased emerin stability and impairment of emerin-mediated processes. ß-DG and emerin are reciprocally required for their optimal targeting within the NE, as shown by immunofluorescence, western blotting and immunoprecipitation assays using emerin variants with mutations in the TM domain and B-lymphocytes of a patient with EDMD. In summary, we demonstrated that ß-DG plays a role as an emerin interacting partner modulating its stability and function.
Assuntos
Distroglicanas/metabolismo , Proteínas de Membrana/metabolismo , Distrofia Muscular de Emery-Dreifuss/metabolismo , Proteínas Nucleares/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Linfócitos B/metabolismo , Sítios de Ligação , Linhagem Celular , Células Cultivadas , Distroglicanas/química , Distroglicanas/genética , Células HeLa , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Distrofia Muscular de Emery-Dreifuss/genética , Mutação , Membrana Nuclear/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/genética , Ligação ProteicaRESUMO
The LMNA gene is associated to a huge broad of phenotypes, including congenital Emery-Dreifuss muscular dystrophy and late-onset LMNA-related muscular dystrophy. In these forms, muscle weakness, contractures, and cardiac impairment are common. In an autosomal dominant pedigree including 5 affected patients, NGS molecular analysis performed in 6 relatives identifies the heterozygous c.1129C>T p.Arg377Cys variant in the exon 6 of the LMNA gene in three of them. Clinical, laboratorial, imaging investigation of these affected patients showed a significant clinical variability: the father presented subclinical imaging muscular dystrophy masqueraded as radiculopathy. One of his sons presented cardiac arrhythmia, muscular weakness, elbow contractures, and intranuclear pseudoinclusions on muscle biopsy. A second son presented only decreased tendon reflexes. Two other brothers presenting myalgia and cramps were not carriers of the same mutation in the LMNA gene. Early diagnosis, considering these variable phenotype and genotype, is important for genetic counseling, as well as cardiac, and rehabilitation management.
Assuntos
Variação Biológica da População , Lamina Tipo A/genética , Distrofia Muscular de Emery-Dreifuss/patologia , Linhagem , Adulto , Diagnóstico Diferencial , Feminino , Testes Genéticos , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Muscular de Emery-Dreifuss/diagnóstico por imagem , Distrofia Muscular de Emery-Dreifuss/genética , Mutação de Sentido IncorretoRESUMO
The Emery-Dreifuss muscular dystrophy is a form of muscular dystrophy that frequently presents early contractures and cardiac conduction defects, caused by emerin deficiency in the inner nuclear membrane of the muscular fibers. A 19-years-old man it presented muscle weakness and hypotrophy in the proximal upper and lower limbs, dysphagia and early contractures in elbows and ankles, with familiar history compatible with X-linked inheritance form. The investigation showed increased serum creatinekinase levels electrocardiogram had a first degree atrioventricular block and right bundle branch block normal electromyography and nerve conduction study muscle biopsy disclosed myopathic characteristics and nuclear protein immunohystochemical analysis showed deficiency of emerin. The clinical and genetics manifestations, laboratorial and electromyography changes, as well as, the study of the pattern of inheritance for genetic counseling are discussed.
Assuntos
Proteínas de Membrana/análise , Distrofia Muscular de Emery-Dreifuss/diagnóstico , Proteínas Nucleares/análise , Adulto , Biomarcadores/análise , Biópsia , Creatina Quinase/sangue , Eletrocardiografia , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/etiologia , Humanos , Imuno-Histoquímica , Masculino , Distrofia Muscular de Emery-Dreifuss/complicações , Distrofia Muscular de Emery-Dreifuss/genéticaRESUMO
A distrofia muscular de Emery-Dreifuss é uma forma de distrofia muscular freqüentemente associada a contraturas articulares e defeitos de condução cardíaca, que pode ser causada pela deficiência da proteína emerina na membrana nuclear interna das fibras musculares. Descrevemos o caso de um homem de 19 anos com diminuição de força muscular, hipotrofia nas cinturas escapular e pélvica, disfagia, contraturas articulares em cotovelos e tornozelos, apresentando história familiar compatível com herança ligada ao cromossomo X. A investigação mostrou creatinaquinase sérica elevada, eletrocardiograma com bloqueio atrioventricular de primeiro grau e bloqueio de ramo direito, eletroneuromiografia normal, biópsia muscular com alterações miopáticas e a análise por imuno-histoquímica mostrou deficiência de emerina. São discutidas as manifestações clínicas e genéticas, alterações laboratoriais e eletroneuromiográficas, bem como, a importância do estudo do padrão de herança no aconselhamento genético destas famílias.
Assuntos
Adulto , Humanos , Masculino , Proteínas de Membrana/análise , Distrofia Muscular de Emery-Dreifuss/diagnóstico , Proteínas Nucleares/análise , Biópsia , Biomarcadores/análise , Creatina Quinase/sangue , Eletrocardiografia , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/etiologia , Imuno-Histoquímica , Distrofia Muscular de Emery-Dreifuss/complicações , Distrofia Muscular de Emery-Dreifuss/genéticaRESUMO
We report on a man that had weakness of humeroperoneal distribution associated with limited range of motion of the cervical spine and elbows since he was 5 years old. At age 26 he developed tachycardia episodes. A complex arrhythmia was discovered, and a nodal ablation was done with a cardiac pacemaker implanted. The patient had an arrhythmia and sudden death followed this. Emery-Dreifuss muscular dystrophy is a rare recessive X-linked muscular disorder where mixed patterns in electromyography and muscle histology (neurogenic and/or myopathic) have caused nosological confusion. The autopsy findings are here described and correlated to the clinical features in an attempt to better understand the ambiguous findings concerning the process etiology.
Assuntos
Distrofia Muscular de Emery-Dreifuss/patologia , Adulto , Biópsia , Evolução Fatal , Humanos , Masculino , Músculo Esquelético/patologiaRESUMO
We report on a man that had weakness of humeroperoneal distribution associated with limited range of motion of the cervical spine and elbows since he was 5 years old . At age 26 he developed tachycardia episodes. A complex arrhythmia was discovered, and a nodal ablation was done with a cardiac pacemaker implanted. The patient had an arrhythmia and sudden death followed this. Emery-Dreifuss muscular dystrophy is a rare recessive X-linked muscular disorder where mixed patterns in electromyography and muscle histology (neurogenic and/or myopathic) have caused nosological confusion. The autopsy findings are here described and correlated to the clinical features in an attempt to better understand the ambiguous findings concerning the process etiology
Assuntos
Humanos , Masculino , Adulto , Distrofia Muscular de Emery-Dreifuss/patologia , Evolução FatalRESUMO
Emery-Dreifuss dystrophy, an X-linked disorder, is a recently recognized distinct neuromuscular disease with special pediatric implications. We describe three affected boys with the typical early contractures and weakness. Two patients are from a large kindred that includes older affected males and carrier females, both of whom had lethal cardiac disease by mid-adulthood. The atrial arrhythmias are treatable by pacemaker if the diagnosis is established beforehand.