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Autosomal-dominant distal myopathy with a myotilin S55F mutation: sorting out the phenotype
  1. J Berciano1,
  2. E Gallardo2,
  3. R Domínguez-Perles3,
  4. E Gallardo3,
  5. A García4,
  6. R García-Barredo2,
  7. O Combarros1,
  8. J Infante1,
  9. I Illa3
  1. 1
    Service of Neurology, “Marqués de Valdecilla” University Hospital (IFIMAV), “Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas” (CIBERNED), University of Cantabria, Santander, Spain
  2. 2
    Service of Radiology, “Marqués de Valdecilla” University Hospital (IFIMAV), University of Cantabria, Santander, Spain
  3. 3
    Service of Neurology and Laboratory of Experimental Neurology, “Hospital de la Santa Creu i Sant Pau i Institut de Recerca de HSCSP, Universitat Autonoma”, Barcelona, Spain
  4. 4
    Service of Clinical Neurophysiology, “Marqués de Valdecilla” University Hospital (IFIMAV), University of Cantabria, Santander, Spain
  1. Prof. José Berciano, Service of Neurology, “Marqués de Valdecilla” University Hospital, 39008 Santander, Spain; jaberciano{at}


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 assessments, magnetic resonance imaging (MRI) of lower limb musculature, histochemical and immunohistochemical studies of a muscle biopsy and mutation analysis of the myotilin gene.

Results: Both symptomatic patients, aged 76 and 61 years, presented with late-onset, distal lower-limb weakness involving the ankle and toe flexo-extensor muscles extending up to the thigh muscles; there was mild weakness of the intrinsic hand musculature in the eldest patient. Electromyography revealed a myopathic pattern. Serum creatine kinase levels were slightly 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 the thigh musculature, mainly involving the biceps, femoris, semimembranosus, vasti and glutei muscles; intrinsic foot musculature was involved but to a lesser degree. In all six gene mutation carriers, aged from 21 to 63 years, clinical examinations showed no myopathic signs. MRI was normal in the youngest individual, whereas in the remaining five individuals the outstanding finding was fatty infiltration of the soleus muscles.

Conclusions: Myotilin S55F mutations may cause a clinically distinct autosomal-dominant late-onset and lower-limb distal myopathic syndrome involving all four leg muscle compartments. MRI helps to reliably depict the topography of fatty muscle atrophy and to detect early leg muscle changes in asymptomatic gene mutation carriers.

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  • Funding: Supported by “Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV)” and CIBERNED (CB06/05/0037 and CB06/05/0030), “Instituto de Salud Carlos III”, Madrid, Spain.

  • Competing interests: None.

  • Patient consent: Patient consent was obtained to publish the figures in this paper.