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. They usually manifest in adulthood. Sometimes the heart muscle is also involved. Until now myofibrillar myopathies and limb-girdle dystrophies have been distinguished histologically, with clinical findings, electromyography and nerve conduction velocity also being considered in the diagnostic decision.
Categorization and classification is now more likely to be based 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 intermyofibrillar 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 Neuromuscul 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