Description

Scientific Background

This is a clinically and genetically heterogeneous group of progressive skeletal muscle diseases. They are characterized by progressive muscle weakness and atrophy, similar to the group of limb-girdle dystrophies and usually manifest in adulthood. Sometimes the heart muscle is also involved. Myofibrillar myopathies and limb-girdle dystrophies have mainly been distinguished histologically, with clinical findings, electromyography (EMG) and nerve conduction velocity being considered in the diagnostic decision.

Categorization and classification is now based more on the identification of new genes. The gene products are proteins that play a role in the structure or function of the Z-discs within muscle fibers. Pathogenic variants in the genes can lead to progressive disorganization of the intermyofibrillary network, abnormal protein deposits or vacuole formation within the sarcoplasm. Abnormal intracellular desmin-positive protein aggregates can be observed. In this group of patients pathogenic variants are found in the DES gene (desmin) and in other genes. The clinical phenotype covers a broad spectrum, even for variants in the same gene. Pure cardiomyopathies are also known.

References

Batonnet-Pichon et al. 2017 J of Neuromusc Dis 4:1 / Kley et al. 2016 Curr Opin Neurol 29:628 / Selcen et Engel 2012, GeneReviews® / Schröder et Schoser 2009, Brain Pathol 19:483