Myofibrillar myopathies: State of the art, present and future challenges

Area of Science:

• Neurology
• Genetics
• Histopathology

Background:

• Myofibrillar myopathies (MFM) are a group of inherited muscle disorders characterized by specific histological findings.
• Key features include abnormal protein aggregation, vacuoles, and Z-disk disorganization.
• The genetic basis of MFM is complex, involving multiple genes, with evolving diagnostic criteria.

Purpose of the Study:

• To review current knowledge on the six main genes associated with MFM.
• To present clinical and genetic findings from French reference centers.
• To emphasize diagnostic challenges and the role of genetic testing.

Main Methods:

• Review of existing literature on MFM genetics and clinical presentations.
• Analysis of patient data from two French reference centers (Paris and Marseilles).
• Focus on histological features, muscle imaging, and genetic testing.

Main Results:

• Six genes (DES, CRYAB, LDB3/ZASP, MYOT, FLNC, BAG3) are primarily implicated in MFM.
• Other genetic entities, like FHL1 myopathy and titin-related myopathies, are increasingly recognized as part of the MFM spectrum.
• Muscle imaging plays a crucial role due to potential focal histological lesions.

Conclusions:

• Accurate diagnosis of MFM can be challenging due to variable presentation and focal pathology.
• Systematic genetic testing is essential for patients with typical histological findings.
• Continued research and data sharing from reference centers are vital for understanding MFM.