title: Redefining dysferlinopathy phenotypes based on clinical findings and muscle imaging studies.
abstract: BACKGROUND
  The most frequent phenotypes of dysferlin myopathy are limb-girdle muscular dystrophy 2B (LGMD2B) and Miyoshi myopathy (MM). Our objective was to find clinical or MRI markers to differentiate phenotypes of dysferlin myopathy regardless of initial symptoms.
  
  
  METHODS
  This retrospective study included 29 patients with confirmed mutations in the DYSF gene (14 MM, 12 LGMD2B, 1 asymptomatic hyperCKemia, and 2 symptomatic carriers). All underwent an annual clinical examination (Medical Research Council scale), functional status assessment, and creatine kinase, pulmonary, and cardiac testing. For research purposes, we performed lower limb MRI studies in all 29 patients to identify the pattern of muscle impairment and to quantify involvement. Statistical correlations between MRI findings and phenotype, disease duration, and functional status were determined.
  
  
  RESULTS
  The mean clinical follow-up was 6.4 +/- 5.7 years. No significant differences were found in the rate of progression, functional prognosis, or mutations between patients with MM and patients with LGMD2B. The MRI pattern of muscle involvement was the same for patients with MM and patients with LGMD2B. The adductor magnus and gastrocnemius medialis were the first to be impaired in both phenotypes. The progression of muscle involvement correlated with clinical status.
  
  
  CONCLUSIONS
  Splitting dysferlin myopathy into separate phenotypes does not reveal significant differences in terms of rate of progression, prognosis, genotype, or MRI pattern. The finding that proximal and distal muscles are already impaired in the MRI at onset in both MM and LGMD2B favors grouping all phenotypes under the term dysferlin myopathy.
authors.affiliation: Department of Neurology, Hospital de la Santa Creu i Sant Pau, C/Pare Claret 167, 08025 Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Paradas
authors.forename: J
authors.initials: J
authors.lastname: Llauger
authors.forename: J
authors.initials: J
authors.lastname: Diaz-Manera
authors.forename: R
authors.initials: R
authors.lastname: Rojas-García
authors.forename: N
authors.initials: N
authors.lastname: De Luna
authors.forename: C
authors.initials: C
authors.lastname: Iturriaga
authors.forename: C
authors.initials: C
authors.lastname: Márquez
authors.forename: M
authors.initials: M
authors.lastname: Usón
authors.forename: K
authors.initials: K
authors.lastname: Hankiewicz
authors.forename: E
authors.initials: E
authors.lastname: Gallardo
authors.forename: I
authors.initials: I
authors.lastname: Illa
mesh_terms: D000203:Activities of Daily Living; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D000073939:Dysferlin; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007866:Leg / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins