Clinical phenotype, muscle MRI and muscle pathology of LGMD1F

J Neurol. 2013 Aug;260(8):2033-41. doi: 10.1007/s00415-013-6931-1. Epub 2013 Apr 30.


Of the seven autosomal dominant genetically distinct forms of LGMD so far described, in only four the causative gene has been identified (LGMD1A-1D). We describe clinical, histopathological and muscle MRI features of a large Italo-Spanish kindred with LGMD1F presenting proximal-limb and axial muscle weakness. We obtained complete clinical data and graded the progression of the disease in 29 patients. Muscle MRI was performed in seven patients. Three muscle biopsies from two patients were investigated. Patients with age at onset in the early teens, had a more severe phenotype with a rapid disease course; adult onset patients presented a slow course. Muscle MRI showed prominent atrophy of lower limb muscles, involving especially the vastus lateralis. Widening the patients population resulted in the identification of previously unreported features, including dysphagia, arachnodactyly and respiratory insufficiency. Muscle biopsies showed diffuse fibre atrophy, which evolved with time, chronic myopathic changes, basophilic cytoplasmic areas, autophagosomes and accumulation of myofibrillar and cytoskeletal proteins. The LGMD1F is characterized by a selective involvement of limb muscles with respiratory impairment in advanced stages, and by different degrees of clinical progression. Novel clinical features emerged from the investigation of additional patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Aging / physiology
  • Biopsy
  • Blotting, Western
  • Child
  • Child, Preschool
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Humans
  • Immunohistochemistry
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / pathology*
  • Muscular Dystrophies, Limb-Girdle / genetics
  • Muscular Dystrophies, Limb-Girdle / pathology*
  • Muscular Dystrophies, Limb-Girdle / physiopathology
  • Neurologic Examination
  • Phenotype
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism
  • Young Adult


  • Muscle Proteins
  • Tripartite Motif Proteins
  • TRIM63 protein, human
  • Ubiquitin-Protein Ligases

Supplementary concepts

  • Muscular Dystrophy, Limb-Girdle, Type 1F