Objective: To describe the clinical phenotype of an autosomal dominant pedigree with myotilinopathy.
Methods: Two symptomatic patients and six asymptomatic gene mutation carriers were examined. We performed serum chemistry, electrophysiological study, magnetic resonance imaging (MRI) of lower limb musculature, histochemical and immunohistochemical study on a muscle biopsy, and mutation analysis of the myotilin gene.
Results: Both symptomatic patients, aged 76 and 61, presented with late onset distal lower limb weakness involving ankle and toe flexo-extensor muscles extending up to thigh muscles; there was just mild weakness of intrinsic hand musculature in the elder patient. Electromyography revealed a myopathic pattern. Serum creatin kinase levels were mildly elevated. Muscle biopsy revealed myopathic changes with myotilin- and desmin-positive aggregates. Gene sequencing identified a myotilin S55F mutation. In both patients MRI showed moderate to severe fatty atrophy of all four leg muscle compartments extending up to thigh musculature mainly involving biceps femoris, semimembranosus, vasti and glutei; intrinsic foot musculature was involved but to a lesser degree. In all six gene mutation carriers, aged from 21 to 63, clinical examinations showed no myopathic signs. MRI was normal in the youngest individual, whereas in the remaining five the outstanding finding was fatty infiltration of the soleus muscles.
Conclusions: Myotilin S55F mutation may cause a clinically distinct autosomal dominant late onset and lower limb onset distal myopathic syndrome involving all four leg muscle compartments. MRI helps reliably depict the topography of muscle fatty atrophy and detect early leg muscle changes in asymptomatic gene mutation carriers.
- autosomal dominant distal myopathy
- myotilin S55F mutation