Limb-girdle muscular dystrophy, type 2A is an autosomal recessive, pan-ethnic disorder that is caused by pathogenic variants in the gene CAPN3. This form of muscular dystrophy presents with weakness of the pelvic girdle and legs, and eventually progresses to the upper limbs. Sometimes it presents with weakness of the upper limbs and progresses to the lower limbs. Onset is usually in childhood or early adolescence, although variability exists. Patients are usually wheelchair-bound about 20 years after diagnosis, and death usually occurs in middle age. Some patients also experience weakness of the facial muscles or contractures of the joints. Patients with at least one missense variant may experience a slightly slower rate of progression than those with two null variants, but the severity of the disease appears to be the same.
For information about carrier frequency and residual risk, please see the residual risk table.