Clinicogenetic lessons from 370 patients with autosomal recessive limb-girdle muscular dystrophy

Clin Genet. 2019 Oct;96(4):341-353. doi: 10.1111/cge.13597. Epub 2019 Jul 15.


Limb-girdle muscular dystrophies (LGMD) are a group of genetically heterogeneous disorders characterized by predominantly proximal muscle weakness. We aimed to characterize epidemiological, clinical and molecular data of patients with autosomal recessive LGMD2/LGMD-R in Brazil. A multicenter historical cohort study was performed at 13 centers, in which index cases and their affected relatives' data from consecutive families with genetic or pathological diagnosis of LGMD2/LGMD-R were reviewed from July 2017 to August 2018. Survival curves to major handicap for LGMD2A/LGMD-R1-calpain3-related, LGMD2B/LGMD-R2-dysferlin-related and sarcoglycanopathies were built and progressions according to sex and genotype were estimated. In 370 patients (305 families) with LGMD2/LGMD-R, most frequent subtypes were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related, each representing around 30% of families. Sarcoglycanopathies were the most frequent childhood-onset subtype, representing 21% of families. Five percent of families had LGMD2G/LGMD-R7-telethonin-related, an ultra-rare subtype worldwide. Females with LGMD2B/LGMD-R2-dysferlin-related had less severe progression to handicap than males and LGMD2A/LGMD-R1-calpain3-related patients with truncating variants had earlier disease onset and more severe progression to handicap than patients without truncating variants. We have provided paramount epidemiological data of LGMD2/LGMD-R in Brazil that might help on differential diagnosis, better patient care and guiding future collaborative clinical trials and natural history studies in the field.

Keywords: disease modifier; epidemiology; limb-girdle; muscular dystrophy; natural history.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Alleles
  • Biomarkers
  • Brazil
  • Disease Progression
  • Female
  • Gene Frequency
  • Genes, Recessive*
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Genotype
  • Geography, Medical
  • Humans
  • Male
  • Muscle Weakness
  • Muscular Dystrophies, Limb-Girdle / diagnosis*
  • Muscular Dystrophies, Limb-Girdle / epidemiology
  • Muscular Dystrophies, Limb-Girdle / genetics*
  • Phenotype
  • Sex Factors


  • Biomarkers