- Limb-girdle muscular dystrophy (LGMD) is a descriptive term applied to a clinically and genetically heterogeneous group of childhood or adult onset muscular dystrophies. Average age of onset is 8-15 years.
- LGMD is characterized by weakness and wasting restricted to the limb musculature, proximal greater than distal. Most individuals with LGMD show relative sparing of the heart and bulbar muscles, although exceptions occur, depending on the genetic subtype.
- Onset usually occurs in the lower extremities with proximal weakness, followed by weakness in the upper extremities some years later.
- LGMD type 2A is inherited in an autosomal recessive manner and also referred to as calpainopathy. This is likely the most frequent form of LGMD.
- LGMD 2A is caused by mutation in the gene encoding for calpain-3 resulting in total or partial loss of protein.
- Serum creatine kinase (CK) levels in individuals with LGMD are usually elevated and muscle biopsy reveals dystrophic changes.
- Intra and interfamilial variability has been observed. Serum CK levels can be normal but are often 5-80 times normal and calpain-3 is usually, but not always, absent by IHC.
- Agarwal community from Indian origin has shown two founder mutations in caplain gene.
Gene & Mutation
Mutations in CAPN3 gene (15q15.1-q21.1) cause LGMD 2A (intron18/exon19 & exon 22) commonly known as Agarwal founder mutation responsible to cause LGMD 2A.