Klingels K.,Hasselt University |
Mayhew A.G.,John Walton Muscular Dystrophy Research Center Institute of Genetic Medicine Newcastle upon Tyne |
Duong T.,Stanford University |
Decostre V.,Institute Of Myologie Gh Pitie Salpetriere Paris France |
And 2 more authors.
Developmental Medicine and Child Neurology | Year: 2016
Aim: To develop a patient-reported outcome measure (PROM) assessing upper limb function related to activities of daily living (ADL) that cannot be observed in a clinical setting, specifically for patients with Duchenne muscular dystrophy (DMD) across a wide age range, applicable in the different stages of the disease. Method: The developmental process was based on US Food and Drug Administration guidelines. This included item generation from a systematic review of existing tools and expert opinion on task difficulty and relevance, involving individuals with DMD. Cultural aspects affecting ADL were taken into consideration to make this tool applicable to the broad DMD community. Items were selected in relation to a conceptual framework reflecting disease progression covering the full range of upper limb function across different ADL domains. Results: After pilot testing and iterative Rasch analyses, redundant or clinically irrelevant items were removed. The final questionnaire consists of 32 items covering four domains of ADL (food, self-care, household and environment, leisure and communication). Test-retest reliability was excellent. Interpretation: A DMD-specific upper limb PROM was developed on the basis of clinical relevance and psychometric robustness. Its main purpose is to document the patient self-reported natural history of DMD and assess the efficacy of interventions. © 2016 Mac Keith Press.
Willis T.A.,John Walton Muscular Dystrophy Research Center Institute of Genetic Medicine Newcastle upon Tyne |
Wood C.L.,John Walton Muscular Dystrophy Research Center Institute of Genetic Medicine Newcastle upon Tyne |
Hudson J.,John Walton Muscular Dystrophy Research Center Institute of Genetic Medicine Newcastle upon Tyne |
Polvikoski T.,Northumbria University |
And 4 more authors.
Clinical Genetics | Year: 2016
Four and a half LIM protein 1 (FHL1/SLIM1) has recently been identified as the causative gene mutated in four distinct diseases affecting skeletal muscle that have overlapping features, including reducing body myopathy, X-linked myopathy, X-linked dominant scapuloperoneal myopathy and Emery-Dreifuss muscular dystrophy. FHL1 localises to the sarcomere and the sarcolemma and is believed to participate in muscle growth and differentiation as well as in sarcomere assembly. We describe in this case report a boy with a deletion of the entire FHL1 gene who is now 15years of age and presented with muscle hypertrophy, reduced subcutaneous fat, rigid spine and short stature. This case is the first, to our knowledge, with a complete loss of the FHL1 protein and MAP7D3 in combination. It supports the theory that dominant negative effects (accumulation of cytotoxic-mutated FHL1 protein) worsen the pathogenesis. It extends the phenotype of FHL1-related myopathies and should prompt future testing in undiagnosed patients who present with unexplained muscle hypertrophy, contractures and rigid spine, particularly if male. © 2016 John Wiley & Sons A/S.