Limb-girdle muscular dystrophy type 2A (LGMD2A), also known as calpainopathy encompasses a range of disorders characterized by muscle weakness stemming from a deficiency of the calpain-3 protein.
LGMD2A primarily affects muscle strength in the hip, shoulder, and abdominal regions, with the rate of muscle weakening varying widely, often necessitating the use of a wheelchair. Additional features may include calf muscle enlargement, mild muscle shortening, joint rigidity, and shoulder blade winging. Most individuals with LGMD2A live into adulthood, with respiratory or heart complications being the primary causes of death. Symptoms exhibit significant variation, even within the same family, with some individuals experiencing mild or nearly asymptomatic courses while others face severe, potentially life-threatening symptoms. Typically, symptoms manifest in early adolescence, although onset during childhood or adulthood is possible. Three distinct presentations have been identified: pelvofemoral muscular dystrophy (Leyden-Moebius LGMD), scapulohumeral muscular dystrophy (Erb LGMD), and hyperCKemia (elevated creatine kinase levels without apparent symptoms).
LGMD2A is caused by pathogenic (disease-causing) variants in the CAPN3 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.