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.

ObjectiveTo analyze the modulation of the phenotype in manifesting carriers of recessive X-linked myotubular myopathy (XLMTM), searching for possible genetic modifiers.MethodsTwelve Brazilian families with XLMTM were molecularly and clinically evaluated. In 2 families, 4 of 6 and 2 of 5 manifesting female carriers were identified. These females were studied for X chromosome inactivation. In addition, whole-exome sequencing was performed, looking for possible modifier variants. We also determined the penetrance rate among carriers of the mutations responsible for the condition.ResultsMutations in the MTM1 gene were identified in all index patients from the 12 families, being 4 of them novel. In the heterozygotes, X chromosome inactivation was random in 3 of 4 informative manifesting carriers. The disease penetrance rate was estimated to be 30%, compatible with incomplete penetrance. Exome comparative analyses identified variants within a segment of 4.2 Mb on chromosome 19, containing the killer cell immunoglobulin-like receptor cluster of genes that were present in all nonmanifesting carriers and absent in all manifesting carriers. We hypothesized that these killer cell immunoglobulin-like receptor variants may modulate the phenotype, acting as a protective factor in the nonmanifesting carriers.ConclusionsAffected XLMTM female carriers have been described with a surprisingly high frequency for a recessive X-linked disease, raising the question about the pattern of inheritance or the role of modifier factors acting on the disease phenotype. We demonstrated the possible existence of genetic mechanisms and variants accountable for the clinical manifestation in these women, which can become future targets for therapies.

Objetivo: verificar se as informações dadas pela ABRELA permitem acesso aos recursos disponíveis (informativos, humanos, de suporte e material); se as expectativas foram atingidas e se há diferença de acesso aos recursos entre São Paulo (SP) e outros Estados. Método: 30 pacientes foram cadastrados na ABRELA (15 do estado de SP e 15 dos demais estados), com diagnóstico de esclerose lateral amiotrófica (ELA) confirmado há pelo menos um ano. Não foram avaliados pacientes com a forma de paralisia bulbar progressiva. Aplicou-se um questionário semi-estruturado com identificação pessoal, questões sobre a doença e, pertinentes ao acesso a recursos. Resultados: Eram 83,3% casados, 60% do sexo masculino e média de idade de 56,2 ± 2,180 anos. Mais da metade possui até dois cuidadores (63%), sendo o cônjuge o principal cuidador (31,6%). O suporte da comunidade está presente em 80% dos casos; porém 76,7% relatam a necessidade de outras assistências terap êuticas (hidroterapia, sede regional da ABRELA e atendimento domiciliar). Conclusões: apesar dos recursos estarem disponíveis, o acesso é maior por parte daqueles residentes no estado de SP, onde está localizada a sede da Associação. Justifica-se, assim, a necessidade de maiores investimentos para implantação de ABRELAs regionais bem como para formação e orientação de profissionais.