Background: Our understanding of the genetic basis of muscle disease has grown dramatically over the last few years. Gene tests are now available for the diagnosis of several conditions and molecular research is providing greater understanding of pathogenesis.
Material and methods: This article reviews some of these advances.
Results: Duchenne and Becker muscular dystrophies are allelic disorders that differ in age of onset and severity. This can be explained at the genetic level by different types of mutations, one giving total protein loss (Duchenne) whereas the other results in a less severe deficiency (Becker). Facioscapulohumeral muscular dystrophy is associated with deletion involving repeated DNA in the sub-telomeric region of chromosome 4. No single gene responsible for this disorder has been identified, but we know that deletion size correlates with disease severity. Interestingly, complete removal of this region does not result in disease. Limb girdle muscular dystrophies share a similar phenotype, but genetic and protein studies show that this can be the result of mutation in very different types of protein including a protease. There are now two forms of myotonic dystrophy, both caused by what are called expansions, an increased number of triplet repeats. Both forms demonstrate multisystem involvement and in both cases more than one genetic mechanism has been shown to be active. Certain muscle diseases appear more common in Scandinavia. Amongst these are the distal myopathies in which one type prevalent in Finland has been linked to defects in the titin protein.
Interpretation: The challenge is now to translate the advances in our understanding of genetic mechanism into potential forms of treatment. Unfortunately, while much research is focused on techniques such as gene therapy, myoblast transplantation and the use of stem cells, these have not yet born fruit.