LGMD2B versus Miyoshi myopathy

I asked the good people at the Jain Foundation (https://www.jain-foundation.org/), an organization devoted to the treatment of Limb Girdle Muscular Dystrophy 2B/Miyoshi myopathy, to help me understand the difference between the two diseases. The Jain Foundation’s director of research, Laura Rufibach, PhD, gave the following informative response:

“Limb-girdle muscular dystrophy and Miyoshi Myopathy are general clinical designations that are given depending on the initial pattern of muscle weakness seen in patients. LGMD is characterized by proximal muscle weakness, while Miyoshi Myopathy is characterized by distal muscle weakness.

“There are 19 genetically defined forms of LGMD (6 dominant and 13 recessive). Clinically, many of the LGMDs are similar and the exact form can only be identified by protein screening or the identification of mutations. For LGMD2B, the “2” signifies the recessive nature of the disease and the “B” indicates that the LGMD is caused by a problem with the dysferlin protein.

“Miyoshi Myopathy is also a genetically heterogeneous form of muscular dystrophy with 3 different linked loci identified to date. At present, mutations in only one gene have been identified that are known to result in Miyoshi Myopathy. That gene, like LGMD2B, is dysferlin.

“Therefore, LGMD2B and Miyoshi Myopathy (caused by mutations in dysferlin) are allelic disorders. The initial clinical presentation (i.e. pattern of muscle weakness) of LGMD2B and Miyoshi Myopathy are very distinct. However as the disease progresses, the majority of patients begin to show a mixture of both distal and proximal weakness. Some patients even initially present with a mixture of both proximal and distal muscle weakness. There are even some reports of both an LGMD2B and Miyoshi Myopathy presentation occurring in siblings within the same family with the same genetic mutations.

“Therefore from my perspective as a geneticist, LGMD2B and Miyoshi Myopathy (resulting from mutations in dysferlin) are the same disease and the variations in clinical presentation are the result of other modifiers (genetic or environmental) that have yet to be identified. Given this fact both LGMD2B and Miyoshi Myopathy could be treated with the same genetic therapeutic approaches (i.e. gene therapy, exon skipping, etc). This is why we include both types of patients in our patient registry."