title: Autosomal-dominant distal myopathy with a myotilin S55F mutation: sorting out the phenotype.
abstract: 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.
authors: Service of Neurology, Marqués de Valdecilla University Hospital, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, University of Cantabria, Santander, Spain. jaberciano@humv.es
authors: J
authors: J
authors: Berciano
authors: E
authors: E
authors: Gallardo
authors: R
authors: R
authors: Domínguez-Perles
authors: E
authors: E
authors: Gallardo
authors: A
authors: A
authors: García
authors: R
authors: R
authors: García-Barredo
authors: O
authors: O
authors: Combarros
authors: J
authors: J
authors: Infante
authors: I
authors: I
authors: Illa
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D001284:Atrophy; D001706:Biopsy; D002869:Chromosome Aberrations; D003062:Codon / Q000235:genetics; D064211:Connectin; D003402:Creatine Kinase / Q000097:blood; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004576:Electromyography; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D006580:Genetic Carrier Screening; D006801:Humans; D007866:Leg; D008279:Magnetic Resonance Imaging; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D018908:Muscle Weakness / Q000175:diagnosis / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology; D009133:Muscular Atrophy / Q000175:diagnosis / Q000235:genetics; D009135:Muscular Diseases / Q000175:diagnosis / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis / Q000235:genetics; D020125:Mutation, Missense; D009460:Neurologic Examination; D010375:Pedigree; D010641:Phenotype; D010649:Phenylalanine / Q000235:genetics*; D012694:Serine / Q000235:genetics*
chemical_list: D003062:Codon; D064211:Connectin; D003598:Cytoskeletal Proteins; C577290:MYOT protein, human; D008840:Microfilament Proteins; D009124:Muscle Proteins; D012694:Serine; D010649:Phenylalanine; D003402:Creatine Kinase