Abstract:
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Myofibrillar myopathies (MMF), defined by an abnormal accumulation of diverse proteins within muscle fibers, correspond to an expanding number of genetic abnormalities. Material and methods: In our department, 64 patients from 43 families present with histologically defined MMF. We systematically reviewed the clinical and paraclinical data of genetically characterized patients, including systematic cardiologic and electromyographic assessment, search for ocular abnormalities and muscle imaging. Results: A mutation has been found in 17 families (27 cases), including 11 desminopathies (15 cases), 3 zaspopathies (7 cases), 2 myotilinopathies (2 cases) and 1 alpha-B crystallinopathy (3 cases). No filaminopathy has been found yet. Desminopathies were characterized by an early onset (mean age at first symptoms 31 years), lower limb distal weakness predominating on distal muscles in two thirds of cases. Heart involvement was present in all cases, and was the presenting sign of the disease in one half of cases. It varied from conduction abnormalities to dilated, hypertrophic or restrictive cardiomyopathies. A restrictive syndrome was present 65% of cases. Zaspopathies appeared as distal myopathies affecting both anterior and posterior compartments of legs on imaging, with no significant cardiac or respiratory involvement, with a very slow progression. Mean age at onset was 45 years. Myotilinopathies were characterized in both our cases by weakness of foot dorsiflexors occurring after 65 years. Alpha B crystallinopathy presented as a 30 year-old onset, proximal and axial myopathy, associated with cataract. Discussion: MMF present clinically as a group of heterogeneous disorders. However, heart involvement, especially when severe and associated with respiratory involvement, should still lead to consider desmin mutations. On the other hand, late-onset, slowly progressive deficit should orientate towards myotilin and ZASP mutations. As noticed in previous series, clinical and imaging characteristics help in distinguishing the different subsets of MMF.
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