Responsiveness of upper limb scales and trunk control for the evolution of patients with duchenne muscular dystrophy / Responsividade de escalas de membro superior e controle de tronco na evolução de pacientes com distrofia muscular de duchenne

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.

Functional performance and muscular strength in symptomatic female carriers of Duchenne muscular dystrophy / Desempenho funcional e força muscular em portadoras sintomáticas de distrofia muscular de Duchenne

Abstract Duchenne muscular dystrophy (DMD) usually affects men. However, women are also affected in rare instances. Approximately 8% of female DMD carriers have muscle weakness and cardiomyopathy. The early identification of functional and motor impairments can support clinical decision making. Objective: To investigate the motor and functional impairments of 10 female patients with dystrophinopathy diagnosed with clinical, pathological, genetic and immunohistochemical studies. Methods: A descriptive study of a sample of symptomatic female carriers of DMD mutations. The studied variables were muscular strength and functional performance. Results: The prevalence was 10/118 (8.4%) symptomatic female carriers. Deletions were found in seven patients. The age of onset of symptoms in female carriers of DMD was quite variable. Pseudohypertrophy of calf muscles, muscular weakness, compensatory movements and longer timed performance on functional tasks were observed in most of the cases. Differently from males with DMD, seven female patients showed asymmetrical muscular weakness. The asymmetric presentation of muscle weakness was frequent and affected posture and functionality in some cases. The functional performance presents greater number of compensatory movements. Time of execution of activities was not a good biomarker of functionality for this population, because it does not change in the same proportion as the number of movement compensations. Conclusion: Clinical manifestation of asymmetrical muscle weakness and compensatory movements, or both can be found in female carriers of DMD mutations, which can adversely affect posture and functional performance of these patients.

Resumo A distrofia muscular de Duchenne (DMD) geralmente afeta indivíduos do sexo masculino. No entanto, mulheres também são acometidas em casos raros. Aproximadamente 8% das portadoras de DMD têm fraqueza muscular ou cardiomiopatia. A identificação precoce das alterações funcionais e motoras pode alterar a tomada de decisão clínica. Objetivo: Investigar as deficiências motoras e funcionais de 10 pacientes do sexo feminino com distrofinopatia diagnosticada por estudos clínicos, patológicos, genéticos e imuno-histoquímicos. Método: Estudo descritivo de uma amostra de portadoras sintomáticas de mutações DMD. As variáveis estudadas foram força muscular e desempenho funcional. Resultados: A prevalência foi de 10/118 (8,4%) de portadoras sintomáticas de DMD. Foram encontradas deleções em sete pacientes. A idade de início dos sintomas em portadoras de DMD foi variável. Pseudo-hipertrofia de panturrilhas, movimentos compensatórios, fraqueza muscular e aumento no tempo de execução de tarefas funcionais foram observados na maioria dos casos. Diferentemente dos homens com DMD, sete pacientes apresentaram fraqueza muscular assimétrica. A apresentação assimétrica da fraqueza muscular foi frequente, podendo afetar a postura e a funcionalidade. O desempenho funcional geralmente apresenta aumento no número de movimentos compensatórios. Não podemos sempre considerar o tempo como um bom marcador de funcionalidade para essa população, uma vez que não muda na mesma proporção que o número de compensações em todas essas pacientes. Conclusão: Fraqueza muscular assimétrica e movimentos compensatórios, ou ambos, podem ser encontrados em portadoras sintomáticas de DMD, o que pode afetar a postura e a funcionalidade dessas pacientes.

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.

Distrofia muscular de Duchenne: incidencia, prevalencia, características sociodemográficas y clínicas de pacientes ingresados a Teletón Chile desde 1993 a 2013 / Duchenne muscular dystrophy: incidence, prevalence, sociodemographic and clinical characteristics of patients admitted to Teletón Chile from 1993 to 2013

Duchenne muscular dystrophy (DMD) in their natural evolution leads to loss of ambulation between 7 and 13 years of age and death in adolescence close to 20 years. The estimated global incidence is of 1/3,500 male births; data in Chile is unknown. Objective: To estimate the incidence, prevalence of DMD and to describe clinical and sociodemographic characteristics of patients admitted to Teletón-Chile between 1993 and 2013. Patients and Method: A descriptive, retrospective, longitudinal study with review of medical records and database at Teletón. 462 DMD patients were admitted during the study period. Results: The incidence and prevalence in Teletón was of 1/6,558 male live births and the prevalence of 11.51 [CI 10.46 to 12.56] 105 men < 30 years. The average age of first consultation was 6.7 +/- 3.4 years, with mild or moderate functional level (65.6 percent). At the end of the study 67 percent were wheelchair users, with medical prescription at 10.8 +/- 3.3 years. 52.2 percent of patients were classified as extreme poverty, attended at Teletón centers of the central region (55.2 percent), and current average age of 14.7 +/- 5.7 years. 35.9 percent of DMD patients were dead at an average age of 18.1 +/- 3.5 years. Conclusion: The incidence and prevalence rates of DMD live births for males < 30 years admitted to Teletón, have declined between 1993-2011; as well as the average age of first consultation. The loss of ambulation and the average age of death are comparable with the current literature...

La distrofia muscular de Duchenne (DMD) en su evolución natural, produce pérdida de deambulación entre los 7 y 13 años de edad y la muerte en la adolescencia cercana a los 20 años. La incidencia mundial se estima de 1/3.500 nacimientos masculinos; en Chile se desconoce su magnitud. Objetivo: Estimar tasas de incidencia, prevalencia de DMD y describir características clínicas y sociodemográficas de pacientes ingresados a Institutos Teletón-Chile (IT) entre 1993 y 2013. Pacientes y Método: Estudio descriptivo, retrospectivo, longitudinal, con revisión de fichas clínicas y base de datos de IT. Se identificaron 462 pacientes con DMD, ingresados en el período estudiado. Resultados: La tasa de incidencia en IT fue de 1/6.558 nacidos vivos masculinos y prevalencia de 11,51 [IC: 10,46-12,56] por 105 varones < 30 años. Edad media de primera consulta: 6,7 +/- 3,4 años, con compromiso funcional leve o moderado (65,6 por ciento); al término del estudio el 67 por ciento eran usuarios de silla de ruedas, con prescripción médica a los 10,8 +/- 3,3 años. 52,2 por ciento de los pacientes de extrema pobreza, atendidos en IT zona central del país (55,2 por ciento), edad promedio actual de 14,7 +/- 5,7 años. El 35,9 por ciento estaban fallecidos, a la edad promedio de 18,1 +/- 3,5 años. Conclusión: Las tasas de incidencia y prevalencia de DMD para los nacidos vivos varones < 30 años ingresados a los IT, han disminuido entre 1993-2011; también la edad promedio de primera consulta. La pérdida de la marcha y la edad media de la defunción, son comparables con la literatura...

Deletional mutations of dystrophin gene and carrier detection in eastern India.

Objective. To determine the pattern of deletions of the dystrophin gene, the major class of mutations among the Duchenne and Becker muscular dystrophy patients of eastern India and to analyze the carrier frequency of the female members of the proband’s family. Methods. Deletional mutations occurring in patients have been characterized by multiplex polymerase chain reaction. Carrier state of mothers and sisters of probands were analyzed by either of two methods: 1) typing polymorphic short tandem repeat markers in or around the regions of deletion, by radioactive polymerase chain reaction and 2) quantitative real time amplification of the region of deletion. Results. Deletions were detected in 67 (62.04%) out of 108 male patients, about 76.12% of these being localized in the central hot spot region of the gene, i.e., between exon 42 to exon 53 and 17.91% at the proximal hot spot i.e., between exon 1 to exon 20. In the present study were found 43 types of deletions, out of which 25 (58%) were new deletions, which were not described earlier among the Indian patients. Distribution pattern of deletions in different hot spot regions has been compared with that of other countries and statistical analysis reveals significant difference between countries (p<0.001). Correlation of the pattern of deletion with clinical phenotype of patients has been discussed. Interesting case of germline mosaicism and its implications in counseling has also been discussed. Conclusion. About half the mothers of affected probands were not carriers of the deletion, underscoring the need to use real time techniques for carrier detection.

Distrofia muscular de Duchenne, presentación clínica / Duchenne muscular dystrophy clinical presentation

Background: Duchenne Muscular Dystrophy is an X-link recessive disorder that affects 1 per 3.500 males. Becker Muscular Dystrophy is less common, affecting approximately 1 per 30 000 males. Both diseases are the result of a mutation in the Xp21 gene that encodes for dystrophin. Objective: Describe the clinical manifestations of Duchenne Muscular Dystrophy in patients at our institution. Method: Observational and descriptive study, in which clinical records of 8 patients with Duchenne Muscular Dystrophy were reviewed, with description of their clinical aspects. Results: The mean age at diagnosis was 5 years-old. 6 boys presented developmental delay and 7 deambulation difficulties, being the main reason for medical attendance. 3 patients died during the study period. Conclusions: A multidisciplinary management is required to delay the disease evolution, while it does not have a curative treatment. It is necessary to know the clinical aspects representative of this disease, in order to perform an early diagnosis.

Introducción: La distrofia muscular de Duchenne es una alteración ligada al X recesiva que afecta 1 en 3 500 varones. La distrofia muscular de Becker es menos común, afectando aproximadamente 1 en 30 000 varones. Ambas resultan de la mutación de un gen localizado en Xp21, el cual codifica a la distrofina. Objetivos: Describir el comportamiento clínico de la distrofia muscular de Duchenne en pacientes evaluados en nuestra institución. Pacientes y Métodos: Se realizó un estudio de tipo observacional y descriptivo, donde se revisaron las historias clínicas de ocho pacientes con el diagnóstico de distrofia muscular de Duchenne, donde se describieron los aspectos clínicos y paraclínicos de la entidad. Resultados: El promedio de la edad para el momento del diagnóstico fue de cinco años. Seis presentaron retardo del desarrollo psicomotor y la marcha se encontró alterada en siete pacientes siendo este el principal motivo de consulta junto a caídas frecuentes. Tres pacientes habían fallecido al final del período en estudio. Conclusiones: Se requiere de un tratamiento multidisciplinario para retrasar la evolución de la enfermedad, mientras no se disponga de un tratamiento curativo. Es necesario conocer los aspectos representativos de esta enfermedad para realizar su diagnóstico precoz.

Analysis of dystrophin gene deletions by multiplex PCR in eastern India.

The most common genetic neuromuscular disease of childhood, Duchenne and Becker muscular dystrophy (DMD/BMD) is caused by deletion, duplication or point mutation of the dystrophin gene located at Xp 21.2. In the present study DNA from seventy unrelated patients clinically diagnosed as having DMD/BMD referred from different parts of West Bengal, a few other states and Bangladesh are analyzed using the multiplex polymerase chain reaction (m-PCR) to screen for exon deletions and its distribution within the dystrophin gene. Out of seventy patients forty six (63%) showed large intragenic deletion in the dystrophin gene. About 79% of these deletions are located in the hot spot region i.e, between exon 42 to 53. This is the first report of frequency and distribution of deletion in dystrophin gene in eastern Indian DMD/BMD population.

Dystrophin gene deletions in South Indian Duchenne muscular dystrophy patients.

66 unrelated patients from Southern India with Duchenne Muscular Dystrophy (DMD) were studied for intragenic deletion in 18 exons and Pm region of the DMD gene using multiplex PCR. Of these 41 (62.1%) showed intragenic deletions. 78% of the deletions were located at the distal hotspot region (44-55 exons) and 22% of the deletions were located at the proximal region (exon 2-19). Exon 50 is most frequently deleted. Deletions in isolated cases were significantly more compared to familial cases. The lower incidence reported from South India compared to North India, is suggestive of variations in the Southern and Northern population.