Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses / 中华儿科杂志

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.

Prevalencia de dolor crónico en pacientes con distrofia muscular de Duchenne en etapas no ambulantes / Prevalence of chronic pain in Duchenne muscular dystrophy patients in non-ambulatory stage

INTRODUCTION: Chronic pain is a frequent symptom in patients with Duchenne muscular dystrophy (DMD) as reported, in up to 73%, affecting their normal activities, participation and quality of life; however it is an underdiagnosed symptom, and therefore, undertreated. OBJECTIVE: to establish the prevalence of chronic pain in a population with non-ambulatory DMD attending Instituto Teletón Santiago (ITS). MATERIALS AND METHODS: Descriptive, cross-sectional study in DMD patients of Instituto Teletón Santiago, of 12 years old and older, who were in an early or late non-ambulatory stage. By means of a questionnaire designed by the authors, adapted from 'Brief Pain Inventory' and 'ID-Pain', and administered via telephone, it was possible to obtain data on the presence of acute, chronic pain and its intensity, frequency, location, clinical characteristics and interference with daily life activities and the use of analgesic drugs. Data collected helped to do an estimation of the prevalence of pain in the last week, chronic pain as well as summary measures for location, intensity and clinical characteristics. RESULTS: of 74 active patients with DMD and in compliance with the inclusion criteria, 23 subjects responded the questionnaire (31% response rate); average age was 18.3 years, and 9 months since loss of walking ability; prevalence of acute pain was 13% and 13% for chronic pain; most common localization was in the hips, followed by neck, spine and lower limbs; duration and frequency were variable and of moderate intensity. CONCLUSION: Pain has a lower prevalence in the studied population compared to the literature, however, it affects multiple locations and has an impact on their daily activities, and therefore it is important to record the presence of chronic pain in clinical practice. It is necessary to get a higher response rate in future studies and quantify pain with an instrument developed especially for this population.

INTRODUCCIÓN: El dolor crónico es un síntoma frecuente en pacientes con distrofia muscular de Duchenne (DMD) reportado en hasta un 73%, afectando las actividades, participación y calidad de vida; sin embargo, es un síntoma subdiagnosticado y por ende subtratado. OBJETIVO GENERAL: Determinar prevalencia de dolor crónico en población con DMD en etapa no ambulante que se atiende en Instituto Teletón Santiago (ITS). MATERIALES Y MÉTODOS: Estudio descriptivo, transversal en pacientes con DMD, activos en Instituto Teletón Santiago, de 12 años y más de edad, que se encontraban en etapa no ambulante temprano o tardío. Mediante la aplicación de un cuestionario diseñado por los autores adaptando Brief Pain Inventory e ID-Pain, aplicado vía telefónica, se obtuvo datos sobre la presencia de dolor agudo, crónico, intensidad, frecuencia, localización, tiempo de duración, características clínicas del dolor, interferencia en actividades de vida diaria y uso de fármacos analgésicos. Con los datos recolectados se estimó la prevalencia de dolor crónico, de la última semana y medidas de resumen para localización, intensidad y características clínicas. RESULTADOS: De 74 pacientes activos con diagnóstico de DMD que cumplían criterios de inclusión, se encuestaron 23 sujetos (porcentaje de respuesta de 31%); edad promedio de 18,3 años y 9 años desde pérdida de la marcha; la prevalencia de dolor agudo fue de 13% y de dolor crónico 13%; la localización más frecuente fue en las caderas, seguido por cuello y columna y extremidades inferiores, de duración y frecuencia variable e intensidad moderada. CONCLUSIÓN: El dolor tiene menor prevalencia en la población estudiada en relación con la literatura, sin embargo, afecta múltiples localizaciones e impacta en sus actividades de la vida diaria, por lo que es importante consignar la presencia de dolor crónico en la práctica clínica. Se hace necesario obtener un mayor porcentaje de respuesta en futuros estudios y cuantificar el dolor con un instrumento confeccionado especialmente para esta población.

Desempenho cognitivo através do mini-exame do estado mental na distrofia muscular de Duchenne / Cognitive performance by mini mental state examination in Duchenne muscular dystrophy

OBJETIVO: A distrofia muscular de Duchenne (DMD) é frequentemente associada à deficiência intelectual (DI) e ao prejuízo de funções superiores como leitura, raciocínio, lógica, e memória. O objetivo do estudo foi avaliar o desempenho cognitivo de pacientes com DMD através do Mini-Exame do Estado Mental (MEEM), um teste simples e rápido, usado como primeiro rastreio intelectual, principalmente quando baterias psicométricas complexas, dependentes de psicólogos especializados, não estão disponíveis. MÉTODO: Foi realizado um estudo observacional de trinta e quatro meninos com DMD, com idades entre 8 e 22 anos, separados em dois grupos de acordo com a presença de DI moderada-grave, conforme a definição clínica do funcionamento adaptativo do Manual Estatístico e Diagnóstico de Desordens Mentais 5º edição (DSM-5). Foram avaliados a pontuação no MEEM, marcos do desenvolvimento, independência nas atividades de vida cotidiana e capacidade de alfabetização. RESULTADOS: Os marcos motores e de linguagem estavam atrasados (16 meses), e a média no MEEM foi 21, ponto de corte mais baixo do que verificado em pares da mesma idade. O grupo com DI moderada-grave apresentou uma média de 12 no MEEM, e os subtestes de orientação, atenção e cálculo e linguagem foram os que demonstraram piores desempenhos. O ponto de corte de maior acurácia para distinguir DI moderada-grave nos pacientes com DMD foi 21. CONCLUSÃO: O MEEM apresentou adequada sensibilidade (100%) e especificidade (90%) para o ponto de corte de 21, revelando-se um bom método de triagem cognitiva para DI moderada-grave na DMD.

BACKGROUND: Duchenne muscular dystrophy (DMD) is often associated with intellectual disability (ID) and with impairment of higher mental functions as reading, learning, logical thinking and memory. The goal of this study was evaluate the cognitive performance of DMD patients by Mini-Mental State Examination (MMSE), first bedside screening test, widely used in pediatrics, when neuropsychologic batteries, dependent on specialized psychologists, are not easily available in public health system. METHODS: An observational study of thirty-four boys with DMD, aged 8-22 years, was performed, spliting this group into two sub-groups, according to the presence of moderate-severe, defined by Diagnostic and Statistical Manual of Mental Disorders (DSM-5) adaptative functioning clinical criteria. The MMSE scores, developmental milestones, independence in daily life activities and literacy skills were evaluated. RESULTS: Motor and language milestones were reached with 16 months, later than usual and mean on MMSE was 21, lower than in healthy pairs. In assessment by groups, patients with moderate-severe intellectual disability presented a performance in total MMSE (12) and orientation, attention/calculation and language MMSE subtests lower than patients without ID. The most accurate cutoff value on MMSE to distinguish moderate-severe intellectual disability in DMD patients was 21. CONCLUSION: This study has shown adequate sensitivity and specificity of the MMSE for detection of moderate-severe intellectual disability, with almost 100% sensitivity and 90% specificity for cutoff values of 21 points in DMD.

Características clínicas orales en pacientes con distrofia muscular de Duchenne: estudio descriptivo / Oral characteristics of patients with Duchenne muscular dystrophy (DMD): descriptive study

Introducción: En su evolución, la DMD afecta el sistema estomatognático, situación no explorada en nuestro país. Objetivo: Describir características clínicas orales y asociación con edad, en pacientes con distrofia muscular de Duchenne (DMD). Pacientes y Método: Estudio descriptivo, transversal en 81 pacientes con DMD del Instituto Teletón Santiago, reclutados desde agosto a noviembre 2017, con consentimiento informado. Se efectuó examen clínico diagnóstico para determinar la presencia de caries clínicas (índice ceod/COPD), índice de higiene (Índice Green y Vermillion Simplificado), presencia de maloclusiones y asociaciones de variables orales con edad. Resultados: 65,4% de los pacientes no presentaban caries ni restauraciones, registrándose un promedio COPD = 1,7 ± 1,2 y ceod= 2,1 ± 1,6. El índice de higiene oral promedio fue de 1,9 ± 0,8 considerado como regular. 67,9% de los pacientes presentaba alguna maloclusión, existiendo una relación esta- dísticamente significativa entre presencia de mordida cruzada y grupo etario (p < 0,05). Conclusiones: La menor presencia de caries clínica en pacientes con DMD a lo referido en bibliografía para pacientes sanos, podría atribuirse a los controles periódicos odontológicos otorgados por Instituto Teletón San- tiago. El aumento de las maloclusiones con el avance de la edad, podría ser un indicador del progreso de la enfermedad, ya que los cambios en la función muscular masticatoria son dependientes del tiempo y producen aumento del ancho transversal mandibular originando las maloclusiones más prevalentes como la mordida cruzada y abierta. Palabras clave: Distrofia muscular Duchenne, caries, higiene oral, malo- clusiones.

Oral characteristics of patients with Duchenne muscular dystrophy (DMD). Descriptive study Introduction: In its evolution, Duchenne muscular dystrophy (DMD) affects the stomatognathic system, a condition that has not been studied in our country. Objective: To describe the oral clinical characteristics and age-related association in patients with DMD. Patiens and Method: Cross-sectional des- criptive study including 81 patients with DMD of Instituto Teletón Santiago, recruited from August to November 2017, with informed consent. A diagnostic clinical examination was performed to establish the presence of clinical cavities (DEFT, DMFT index), oral hygiene index (Green and Vermillion, simplified), presence of malocclusions, and age-related associations. Results: 65.4% of patients did not have caries or restorations, showing an average of DMFT = 1.7 ± 1.2, and DEFT= 2.1 ± 1.6. Average oral hygiene index was 1.9 ± 0.8.which is considered regular. 67.9% of the patients had some type of malocclusion, with a statistically significant relation between the presence of cross bite and age group (p < 0.05). Conclusions: Lower presence of clinical caries in DMD patients as referred to in bibliography for healthy patients, could be due to periodic dental controls provided by Instituto Teletón Santiago. Increased ca- ses of malocclusions with age may be an indicator of progress of the disease, because changes in the function of mastication muscles are time-dependent, and increase transverse jaw width, causing more prevalent malocclusions such as cross bite and open bite. Key words: Duchenne muscular dystrophy, caries, oral hygiene, malocclu- sions.

Cuidados com a pessoa com distrofia muscular de Duchenne: revisando as recomendações / Reviewing recommendations to Duchenne muscular dystrophy managment

A Distrofia Muscular de Duchenne (DMD) é doença genética ligada ao X e afeta 1 a cada 3.600-6.000 nascidos vivos. Trata-se de doença progressiva e incapacitante, causada por mutações no gene da distrofina, levando à necrose das fibras musculares. A história natural da doença é de perda da marcha por volta de 13 anos de idade e, sem tratamento, morte antes dos 20 anos por complicações cardiorrespiratórias. Atualmente não há tratamento curativo disponível. As principais recomendações de manejo e cuidado na DMD, visando melhora da qualidade de vida foram publicadas entre 2009 e 2010.O objetivo deste trabalho é estudar o estado da arte destas recomendações. Realizada revisão de literatura com busca sistemática nas bases Pubmed e a BIREME, entre os anos de 2009 e 2016, com chaves de busca (consensus OR guideline OR recommendation) AND (Duchenne OR muscular dystrophy OR neuromuscular disease) e (Protocolo + Duchenne), (Recomendação + Duchenne) e (Consenso + Duchenne). Dos 1.032 artigos encontrados, 32 preencheram todos os critérios de elegibilidade para a revisão, contendo recomendações sobre diagnóstico5, corticoterapia1, manejos ortopédico2, cardíaco5, respiratório14 e cirúrgico1, além de recomendações gerais3 e sobre qualidade de vida1 . Após a cuidadosa leitura e coleta de informações, concluímos que apesar dos vários trabalhos posteriores ao consenso, as recomendações ali contidas permanecem atuais, mas há potenciais acréscimos que deveriam ser considerados em uma nova reunião de consenso. (AU)

Duchenne Muscular Dystrophy (DMD) is a genetic condition, X-related, affecting 1 in 3.600-6.000 births. Is a progressive and handicapping disease, caused by mutations in dystrophin gene, leading to muscle fibers necrosis.Duchenne`s natural hystory is of walking loss about age of 13 and, if no treatment is offered, death due the second decade of life, caused by cardiac and respiratory complications. At the moment, no curative treatment is available. The most important recommendations about DMD management and care were published between 2009 and 2010, as an international consensus organized by American CDC. The purpose of this article is to highlight the state-of-art of these recommendations. We reviewed, using a systematic searching approach, Pubmed and BIREME resources, within 2009 and 2016, using searching keys (consensus OR guideline OR recommendation) AND (Duchenne OR muscular dystrophy OR neuromuscular disease) in pubmed and (Protocolo + Duchenne), (Recomendação + Duchenne), (Consenso + Duchenne) in BIREME. Within total of 1.032 articles inicialy found, 32 were fully accepted to be reviewed, with recommendations about diagnosis5, steroid therapy1, orthopedic2, cardiac5, respiratory14 and surgical managements1. In addition,3 contained general recommendations and1 was about quality of life. After careful reading and information extraction, we concluded that 2010 consensus recommendations remain valid, but there are possible updates that should be considered in a new consensus work. (AU)

Estudios de sueño en pacientes con enfermedades neuromusculares / Sleep breathing disorders in children with neuromuscular diseases

Sleep disordered breathing (SDB) is frencuent en pediatric patients with neuromuscular diseases, generated by different should be conduced early and with a preset frecuency, even more if there is the clinical suspicion of SDB and respiratory function imparment. There are different diagnostic studies, each with its advantages and disadvantages. Polysomnography is considered the reference standard and alternatively, pólygraphy has shown a high level of correlation with respiratory events

Los trastornos respiratorios del sueño (TRS) son frecuentes en los pacientes pediátricos con enfermedades neuromusculares, siendo generados por diversos mecanismos fisiopatológicos que usualmente llevan a hipoventilación y síndrome de apnea hipopnea obstructiva del sueño. la indicación de estudio debe ser precoz y con una periocidad prestablecida, más aún frente a la sospecha clínica del TRS y al constatar alteraciones funcionales respiratorias. Existen disitintos estudios para su diagnóstico y seguimiento, incluso en pacientes con soporte ventilatorio no invasivo; cadas uno con ventajas e inconvenientes particulares. Destaca la polisomnografía, como estándar de referencia y como alternativa, la poligrafía que ha demostrado tener un alto índice de correlación con eventos respiratorios

Mouthpiece ventilation in Duchenne muscular dystrophy: a rescue strategy for noncompliant patients / Ventilação bucal na distrofia muscular de Duchenne: uma estratégia de resgate para pacientes não aderentes

ABSTRACT Objective: To evaluate mouthpiece ventilation (MPV) in patients with Duchenne muscular dystrophy (DMD) who are noncompliant with noninvasive ventilation (NIV). Methods: We evaluated four young patients with DMD who had previously refused to undergo NIV. Each patient was reassessed and encouraged to try MPV. Results: The four patients tolerated MPV well and were compliant with NIV at home. MPV proved to be preferable and more comfortable than NIV with any other type of interface. Two of the patients required overnight NIV and eventually agreed to use a nasal mask during the night. Conclusions: The advantages of MPV over other types of NIV include fewer speech problems, better appearance, and less impact on the patient, eliminating the risk of skin breakdown, gastric distension, conjunctivitis, and claustrophobia. The use of a mouthpiece interface should be always considered in patients with DMD who need to start NIV, in order to promote a positive approach and a rapid acceptance of NIV. Using MPV during the daytime makes patients feel safe and more likely to use NIV at night. In addition, MPV increases treatment compliance for those who refuse to use other types of interfaces.

RESUMO Objetivo: Avaliar a ventilação bucal (VB) em pacientes com distrofia muscular de Duchenne (DMD) não aderentes à ventilação não invasiva (VNI). Métodos: Foram avaliados quatro pacientes jovens com DMD que anteriormente recusaram-se a se submeter à VNI. Cada paciente foi reavaliado e encorajado a tentar VB. Resultados: Os quatro pacientes toleraram bem a VB e aderiram ao uso de VNI em casa. O uso de VB provou ser uma alternativa preferível e mais confortável que o uso de VNI com qualquer outro tipo de interface. Dois dos pacientes necessitaram de VNI noturna e eventualmente aceitaram utilizar uma máscara nasal durante a noite. Conclusões: As vantagens da VB sobre outros tipos de VNI incluem menores problemas na fala, melhor aparência e menor impacto no paciente, eliminando o risco de lesões na pele, distensão gástrica, conjuntivite e claustrofobia. O uso da interface bucal sempre deve ser considerado em pacientes com DMD que necessitam iniciar VNI a fim de promover uma abordagem positiva e uma rápida aceitação da VNI. O uso diurno de VB faz com que os pacientes sintam-se seguros e mais propensos a utilizar VNI à noite. Além disso, a VB aumenta a adesão ao tratamento naqueles pacientes que se recusam a utilizar outros tipos de interfaces.

Early Marker of Myocardial Deformation in Children with Duchenne Muscular Dystrophy Assessed Using Echocardiographic Myocardial Strain Analysis

PURPOSE: As cardiomyopathy is more prevalent and currently the leading cause of death in Duchenne muscular dystrophy (DMD), early detection of myocardial involvement is important. The purpose of this study was to analyze myocardial strain in DMD children, for the possibility of early detection of myocardial dysfunction. MATERIALS AND METHODS: We reviewed medical records of DMD patients who were >10 years of age (15.6±1.6 years, 12.5-18 years), from March 2013 to June 2014. Data of 24 DMD children who underwent echocardiography with three-layer specific myocardial strain were compared with 24 controls (age: 9.3±4.0 years, 5.5-17 years). RESULTS: Epicardial longitudinal strain was lower in DMD (DMD: -9.3±3.8%; control: -12.3±4.3%; p=0.012). Radial strain (DMD: 24.1±11.1%; control: 37.3±25.9%; p=0.027) and strain rate (SR) (DMD: 1.68±0.91; control: 2.42±0.84; p=0.006) on parasternal short axis view were lower in DMD. Circumferential strains in the endocardium (DMD: -17.5±4.7%; control: -24.2±5.3%; p<0.001), myocardium (DMD: -12.7±3.8%; control: -18.0±4.0%; p<0.001), and epicardium (DMD: -8.4±4.0%; control: -12.2±5.0%; p=0.006) were significantly decreased in DMD. Circumferential SRs were lower in the endocardial (DMD: -1.46±0.38; control: -1.78±0.27; p=0.002) and myocardial layers (DMD: 1.02±0.27; control: -1.28±0.22; p=0.001). CONCLUSION: In DMD patients, deteriorations in myocardial circumferential strain might be an indicator for predicting cardiomyopathy.

Orthodontic treatment in a patient with unilateral open-bite and Becker muscular dystrophy. A 5-year follow-up

INTRODUCTION: Becker muscular dystrophy is an X-chromosomal linked anomaly characterized by progressive muscle wear and weakness. This case report shows the orthodontic treatment of a Becker muscular dystrophy patient with unilateral open bite. METHODS: To correct patient's malocclusion, general anesthesia and orthognathic surgery were not considered as an option. Conventional orthodontic treatment with intermaxillary elastics and muscular functional therapy were employed instead. RESULTS: After 36 months, open bite was corrected. The case remains stable after a 5-year post-treatment retention period. .

INTRODUÇÃO: a distrofia muscular de Becker é uma anomalia ligada ao cromossomo X, caracterizada por desgaste muscular progressivo e fraqueza. Este relato de caso mostra o tratamento ortodôntico de um paciente com distrofia muscular de Becker e mordida aberta unilateral. MÉTODOS: na correção de sua má oclusão, anestesia geral e cirurgia ortognática não foram consideradas como uma opção. Tratamento ortodôntico convencional com elásticos intermaxilares e terapia miofuncional foram empregados. RESULTADOS: após 36 meses, a mordida aberta foi corregida. O processo manteve-se estável após um período de cinco anos de retenção de pós-tratamento. .

Laparoscopic guided local injection in the X-linked muscular dystrophy mouse (mdx) diaphragm. An advance in experimental therapies for Duchenne Muscular Dystrophy

PURPOSE: To investigate the development of a laparoscopy technique for local injection into the X-linked muscular dystrophy (mdx) diaphragm. METHODS: It was used 10 mice Balb/C57 and 5 mdx mice and three differents decubitus type were tested: the right lateral, supine, and supine decubitus with 20 degrees elevation of the forelimb. Abdominal caudal face and the 10 intercostal space were tested as spot to introduce the needle into the diaphragm. RESULTS: Supine position with elevation of 20 degrees forelimb and the 10th intercostal space are the beneficial position to apply a local injection. CONCLUSION: It was proved to be possible to perform the laparoscopy technique in the X-linked muscular dystrophy diaphragm and this requires a specific position and technique during the surgery. .

Air stacking: effects on pulmonary function in patients with spinal muscular atrophy and in patients with congenital muscular dystrophy, / Efeitos do treinamento de empilhamento de ar na função pulmonar de pacientes com amiotrofia espinhal e distrofia muscular congênita

OBJECTIVE: Respiratory complications are the main causes of morbidity and mortality in patients with neuromuscular disease (NMD). The objectives of this study were to determine the effects that routine daily home air-stacking maneuvers have on pulmonary function in patients with spinal muscular atrophy (SMA) and in patients with congenital muscular dystrophy (CMD), as well as to identify associations between spinal deformities and the effects of the maneuvers. METHODS: Eighteen NMD patients (ten with CMD and eight with SMA) were submitted to routine daily air-stacking maneuvers at home with manual resuscitators for four to six months, undergoing pulmonary function tests before and after that period. The pulmonary function tests included measurements of FVC; PEF; maximum insufflation capacity (MIC); and assisted and unassisted peak cough flow (APCF and UPCF, respectively) with insufflations. RESULTS: After the use of home air-stacking maneuvers, there were improvements in the APCF and UPCF. In the patients without scoliosis, there was also a significant increase in FVC. When comparing patients with and without scoliosis, the increases in APCF and UPCF were more pronounced in those without scoliosis. CONCLUSIONS: Routine daily air-stacking maneuvers with a manual resuscitator appear to increase UPCF and APCF in patients with NMD, especially in those without scoliosis. .

OBJETIVO: As complicações respiratórias são as principais causas de morbidade e mortalidade em pacientes com doenças neuromusculares (DNM). Os objetivos deste estudo foram determinar os efeitos que o treinamento diário domiciliar com manobras de empilhamento de ar tem na função respiratória de pacientes com amiotrofia espinhal (AE) e distrofia muscular congênita (DMC), e identificar possíveis associações entre deformidades na coluna vertebral e os efeitos das manobras. MÉTODOS: Dezoito pacientes com DNM (dez com DMC e oito com AE) foram submetidos a treinamento diário domiciliar de empilhamento de ar com ressuscitador manual por um período de quatro a seis meses e submetidos a testes de função pulmonar antes e após tal período. Os testes de função pulmonar incluíram medidas de CVF, PFE, a capacidade de insuflação máxima (CIM) e a medida do pico de fluxo de tosse não assistido e assistido (PFTNA e PFTASS, respectivamente). RESULTADOS: Após o uso das manobras de empilhamento de ar no domicílio, houve uma melhora significativa na PFTNA e PFTASS. Nos pacientes sem escoliose, houve também um aumento significativo na CVF. No grupo de pacientes sem escoliose, o ganho na PFTNA e PFTASS foi superior ao do grupo com escoliose. CONCLUSÕES: A utilização rotineira diária de manobras de empilhamento de ar com ressuscitador manual parece melhorar a PFTNA e PFTASS em pacientes com DNM, especialmente naqueles sem escoliose. .

Postural alignment in children with Duchenne muscular dystrophy and its relationship with balance

Background: In Duchenne muscular dystrophy, functional deficits seem to arise from body misalignment, deconditioning, and obesity secondary to weakness and immobility. The question remains about the effects of postural deviations on the functional balance of these children. Objectives: To identify and quantify postural deviations in children with DMD in comparison to non-affected children (eutrophic and overweight/obese), exploring relationships between posture and function. Method: This case-control study evaluated 29 participants aged 6 to 11 years: 10 DMD (DG), 10 eutrophic (EG), and 9 overweight/obese (OG). Digital photogrammetry and SAPo program were used to measure postural alignment and the Pediatric Balance Scale (PBS) was used to measure balance. The Kruskall-Wallis and Dunn post-hoc tests were used for inter-group comparison of posture and balance. Spearman's coefficient tested the correlation between postural and balance variables. Results: The horizontal pelvic alignment data indicated that the anteversion of the DG was similar to that of the OG and twice that of the EG (p<0.05). Compared to the EG, the DG and OG showed an increased forward position of the center of mass (p<0.05). There was a moderate and weak correlation between the PBS score and horizontal pelvic alignment (0.58 and 0.47-left/right). The PBS showed a weak correlation with asymmetries in the sagittal plane (-0.39). The PBS scores for the OG and EG suggest that obesity did not have a deleterious effect on balance. Conclusions: The balance deficit in children with DMD was accompanied by an increased forward position of the center of mass and significant pelvic anteversion that constitutes a compensatory strategy to guarantee similar performance to the children not affected by the disease. .

Effects of yoga breathing exercises on pulmonary function in patients with Duchenne muscular dystrophy: an exploratory analysis / Efeitos de exercícios respiratórios de ioga na função pulmonar de pacientes com distrofia muscular de Duchenne: uma análise exploratória

OBJECTIVE: Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in children, and children with DMD die prematurely because of respiratory failure. We sought to determine the efficacy and safety of yoga breathing exercises, as well as the effects of those exercises on respiratory function, in such children. METHODS: This was a prospective open-label study of patients with a confirmed diagnosis of DMD, recruited from among those followed at the neurology outpatient clinic of a university hospital in the city of São Paulo, Brazil. Participants were taught how to perform hatha yoga breathing exercises and were instructed to perform the exercises three times a day for 10 months. RESULTS: Of the 76 patients who entered the study, 35 dropped out and 15 were unable to perform the breathing exercises, 26 having therefore completed the study (mean age, 9.5 ± 2.3 years; body mass index, 18.2 ± 3.8 kg/m2). The yoga breathing exercises resulted in a significant increase in FVC (% of predicted: 82.3 ± 18.6% at baseline vs. 90.3 ± 22.5% at 10 months later; p = 0.02) and FEV1 (% of predicted: 83.8 ± 16.6% at baseline vs. 90.1 ± 17.4% at 10 months later; p = 0.04). CONCLUSIONS: Yoga breathing exercises can improve pulmonary function in patients with DMD. .

OBJETIVO: A distrofia muscular de Duchenne (DMD) é a forma mais comum de distrofia muscular em crianças, e crianças com DMD morrem prematuramente por causa de insuficiência respiratória. Analisamos a eficácia e segurança de exercícios respiratórios de ioga nessas crianças, bem como os efeitos desses exercícios em sua função respiratória. MÉTODOS: Estudo prospectivo aberto envolvendo pacientes com diagnóstico confirmado de DMD recrutados no ambulatório de neurologia de um hospital universitário em São Paulo (SP). Os participantes aprenderam exercícios respiratórios de hatha ioga e foram instruídos a praticá-los três vezes ao dia durante 10 meses. RESULTADOS: Dos 76 pacientes incluídos no estudo, 35 o abandonaram e 15 não conseguiram realizar os exercícios respiratórios, de modo que 26 pacientes completaram o estudo (média de idade: 9,5 ± 2,3 anos; índice de massa corporal: 18,2 ± 3,8 kg/m2). Os exercícios respiratórios de ioga resultaram em um aumento significativo da CVF em porcentagem do previsto (82,3 ± 18,6% antes do início do programa de exercícios vs. 90,3 ± 22,5% 10 meses depois; p = 0,02) e do VEF1 em porcentagem do previsto (83,8 ± 16,6% antes do início do programa de exercícios vs. 90,1 ± 17,4% 10 meses depois; p = 0,04). CONCLUSÕES: Os exercícios respiratórios de ioga podem melhorar a função pulmonar de pacientes com DMD. .

Comparative study of the kidneys from dystrophic mice

The Duchenne Muscular Dystrophy (DMD) is a recessive genetic disease linked to chromosome X. Thisdisease is characterized by an absence or dysfunction in the expression of dystrophin. Experimental modelsmdxare widely used for the development of research addressing the DMD. The objective of this research is tocontribute to a detailed study of possible renal morphological changes resulting from DMD. We used five pairsof kidneys frommdxmice and five from normal mice, which were subjected to measurement, light microscopy,and scanning electron microscopy. The morphological findings of kidneys frommdxmice are within thepatterns described in animal studies with severe dehydration, which exhibit signs of diffuse hemorrhage inthe cortical and medullary area, while the glomeruli in the cortical region showed a decrease in urinary space,located between the Bowman’s capsule and the inner cell mass of the glomeruli. However, future experimentswith animals in different ages can assist in the proving of the morphological changes found here.

Insuficiência cardíaca congestiva na distrofia muscular de Duchenne: um relato de caso / Congestive heart failure in Duchenne muscular dystrophy: a case report

A Distrofia Muscular de Duchenne é uma doença neuromuscular, hereditária, recessiva, causada por mutações no gene da distrofina. Clinicamente, caracteriza-se por fraqueza muscular progressiva e simétrica. O diagnóstico é feito pela biópsia muscular com imunohistoquímica e o tratamento tem a finalidade de retardar a progressão da disfunção muscular, já que uma causa frequente de óbito é a insuficiência cardiorrespiratória.

Duchenne muscular dystrophy is a neuromuscular disorder with a recessive mode of inheritance caused by a mutation in the dystrophin gene. Clinically, it is characterized by progressive and symmetrical muscle weakness. Diagnosis is made by muscle biopsy with immunohistochemical staining, and treatment aims to slow the progression of muscle dysfunction, because cardiorespiratory failure is a common cause of death.

Changes in Level of the Conus after Corrective Surgery for Scoliosis: MRI-Based Preliminary Study in 31 Patients

BACKGROUND: Detection of postoperative spinal cord level change can provide basic information about the spinal cord status, and electrophysiological studies regarding this point should be conducted in the future. METHODS: To determine the changes in the spinal cord level postoperatively and the possible associated factors, we prospectively studied 31 patients with scoliosis. All the patients underwent correction and posterior fusion using pedicle screws and rods between January 2008 and March 2009. The pre- and postoperative conus medullaris levels were determined by matching the axial magnetic resonance image to the sagittal scout image. The patients were divided according to the change in the postoperative conus medullaris level. The change group was defined as the patients who showed a change of more than one divided section in the vertebral column postoperatively, and the parameters of the change and non-change groups were compared. RESULTS: The mean pre- and postoperative Cobb's angle of the coronal curve was 76.80degrees +/- 17.19degrees and 33.23degrees +/- 14.39degrees, respectively. Eleven of 31 patients showed a lower conus medullaris level postoperatively. There were no differences in the pre- and postoperative magnitude of the coronal curve, lordosis and kyphosis between the groups. However, the postoperative degrees of correction of the coronal curve and lumbar lordosis were higher in the change group. There were also differences in the disease entities between the groups. A higher percentage of patients with Duchene muscular dystrophy had a change in level compared to that of the patients with cerebral palsy (83.3% vs. 45.5%, respectively). CONCLUSIONS: The conus medullaris level changed postoperatively in the patients with severe scoliosis. Overall, the postoperative degree of correction of the coronal curve was higher in the change group than that in the non-change group. The degrees of correction of the coronal curve and lumbar lordosis were related to the spinal cord level change after scoliosis correction.

Avaliação funcional e postural nas distrofias musculares de Duchenne e Becker / Functional and postural evaluation in duchenne and becker muscular dystrophies

Objetivo: O objetivo foi avaliar portadores de distrofia muscular de Duchenne (DMD) e Becker (DMB) por meio de escalas e análise postural. Metodologia: Foram avaliados 13 pacientes, idade 16,75 (± 6,9) sendo 9 DMD, 4 DMB, 7 cadeirantes, 6 não cadeirantes, nas escalas: Índice de Barthel e EK (Egen klassifikation). A avaliação postural sentada foi feita no software SAPO. Resultados: Os dados revelam que: aumento da idade (p<0.01), dependência de cadeira de rodas (p<0.01) e uso de ventilador (p<0.01) indicaram menor independência. Na avaliação postural tanto dos não cadeirantes quanto dos cadeirantes, verificou-se que aumentam os agrupamentos nos cadeirantes, remetendo às limitações impostas pela postura. Conclusão: Esses achados mostram que pacientes com DMD e DMB têm sua funcionalidade e atividades de vida diária debilitadas com o avanço da idade, dependência de cadeira de rodas e uso de ventilador. Assim, associação de escalas com avaliações convencionais e análise postural são ferramentas essenciais para a investigação.

Objective: The objective was to evaluate patients with Duchenne muscular dystrophy (DMD) and Becker (BMD) in scales and postural analysis. Methods: We evaluated 13 patients, age 16.75 (± 6.9) and 9 DMD, BMD 4, 7 wheelchair, wheelchair not 6, on the scales: Barthel Index and EK (Egen Klassifikation). The evaluation was performed in sitting posture software SAPO. Results: Data show that: increasing age (p <0.01), dependence on a wheelchair (p <0.01) and use of ventilator (p <0.01) showed less independence. Postural assessment of both the wheelchair and not the wheelchair, it was found that increase in the wheelchair groups, referring to the restrictions imposed by posture. Conclusion: These findings show that patients with DMD and BMD have its functionality and activities of daily living impaired with advancing age, dependence on a wheelchair and ventilator use. Thus, association of scales with conventional assessments and postural analysis are essential tools for research.

Distrofia muscular de Duchenne: análise eletrocardiográfica de 131 pacientes / Duchenne muscular dystrophy: electrocardiographic analysis of 131 patients

FUNDAMENTO: É conhecido o envolvimento cardíaco em pacientes com distrofia muscular de Duchenne (DMD). O eletrocardiograma (ECG) apresenta algumas alterações típicas na DMD, fato que o torna um exame útil no diagnóstico da lesão cardíaca nessa patologia. OBJETIVO: Avaliar as alterações eletrocardiográficas em pacientes portadores de DMD, correlacionando-as com a idade da população estudada. MÉTODOS: Foram analisados os ECG de 131 pacientes com diagnóstico de DMD. Avaliaram-se diversas variáveis eletrocardiográficas, sendo os pacientes separados em dois grupos: aqueles com e sem alterações, por variável estudada. Fez-se a correlação desses dois grupos com a idade dos pacientes. Foram utilizados os critérios de Garson para estabelecer os parâmetros eletrocardiográficos de normalidade. RESULTADOS: O ECG estava anormal em 78,6 por cento dos pacientes. Todos apresentavam ritmo sinusal. Foram os seguintes os percentuais encontrados para as principais variáveis estudadas: PR curto = 18,3 por cento, ondas R anormais em V1 = 29,7 por cento, ondas Q anormais em V6 = 21,3 por cento, alterações da repolarização ventricular = 54,9 por cento, ondas QS anormais em paredes inferior e/ou lateral alta = 37,4 por cento, distúrbios de condução pelo ramo direito = 55,7 por cento, intervalo QT C prolongado = 35,8 por cento e alargamento do QRS = 23,6 por cento. O teste t não pareado foi utilizado para se estabelecer a correlação da idade com as variáveis eletrocardiográficas estudadas nos dois grupos e, apenas a variável alteração da repolarização mostrou diferença estatisticamente significante. CONCLUSÃO: As alterações eletrocardiográficas na DMD são frequentes, revelando comprometimento cardíaco precoce. Apenas a variável alteração da repolarização ventricular foi mais frequente, porém em faixa etária menor (p < 0,05).

BACKGROUND: Cardiac involvement is known to occur in patients with Duchenne muscular dystrophy (DMD). The electrocardiogram (ECG) shows some typical changes in DMD, which makes it a useful test for the diagnosis of cardiac lesion in this disease. OBJECTIVE: To evaluate the electrocardiographic changes in patients with DMD and to correlate these changes with the age of the population studied. METHODS: ECG of 131 patients diagnosed with DMD were examined. Several electrocardiographic variables were analyzed, and the patients were divided into two groups - one with and one without changes, for each variable studied. The correlation between the two groups and the age of the patients was analyzed. Garson's criteria were used to establish the electrocardiographic parameters of normality. RESULTS: ECG was abnormal in 78.6 percent of the patients. All showed normal sinus rhythm. The following percentages were found for the main variables studied: short PR interval = 18.3 percent; abnormal R waves in V1 = 29.7 percent; abnormal Q waves in V6 = 21.3 percent; abnormal ventricular repolarization = 54.9 percent; abnormal QS waves in inferior and/or upper lateral wall = 37.4 percent; conduction disturbances in right bundle branch = 55.7 percent; prolonged QT C interval = 35.8 percent, and wide QRS = 23.6 percent. Unpaired t test was used to establish the correlation between age and the electrocardiographic variables studied in the two groups. Statistically significant differences were found only for the abnormal repolarization variable. CONCLUSION: Electrocardiographic abnormalities are common in DMD, revealing early cardiac involvement. Only the abnormal ventricular repolarization variable was more frequent, however at a lower age range (p < 0.05).