DID YOU KNOW … there are two ways that calpainopathy can be inherited?

DID YOU KNOW … there are two ways that calpainopathy can be inherited?

In over 90% of calpainopathy cases, it is inherited in an autosomal recessive manner. This means that it can be passed on through families, and that siblings can have the disease. This form of calpainopathy is called Limb Girdle Muscular Dystrophy type 2A (LGMD2A). In this recessive form, for LGMD2A to develop, two copies of the abnormal gene must be present. Individuals who have one copy of the abnormal gene are not affected, but are carriers and can pass the abnormal gene to their children. If both parents are carriers for LGMD2A and neither are affected, there is a 25% chance their child will have LGMD2A, a 50% chance the child will be a carrier for the disease, and a 25% chance the child will have two normal genes (unaffected and not a carrier).

Less commonly, calpainopathy is inherited in an autosomal dominant manner. This is sometimes called LGMD1I or ‘autosomal dominant LGMD2A’. In this form of the disease, individuals with a single copy of the abnormal gene develop muscular dystrophy. If one parent is affected by autosomal dominant calpainopathy, then there is a 50% chance their child will have muscular dystrophy and a 50% chance that the child will have two normal genes (unaffected and not a carrier). Currently, the CAPN3 mutation c.643_663del21 is the only one that has been shown to cause autosomal dominant calpainopathy. [Edited in February 2023 to add that there have now been eight additional autosomal dominant CAPN3 mutations identified: c.598_612del15, c.700G>A, c.759_761del3, c.1327T>C, c.1333G>A, c.1661A>C, c.1706T>C, and c.1715G>C] Additional mutations may also cause autosomal dominant inheritance. This mode of inheritance tends to be associated with a more mild disease course.

To learn more about different forms of inheritance, please visit the Mayo Clinic’s website:

Autosomal recessive inheritance pattern

Autosomal dominant inheritance pattern

To learn more about calpainopathy and the efforts of Coalition to Cure Calpain 3 to drive a cure or treatment please visit our website: www.curecalpain3.org