[Myofibrillar myopaathy]

Area of Science:

• Neurology
• Genetics
• Pathology

Background:

• Myofibrillar myopathy (MFM) encompasses hereditary muscle disorders characterized by myofibril disorganization and cytoplasmic inclusions.
• It includes conditions previously known as desmin-related, storage, cytoplasmic body, spheroid body, reducing body, and hyaline body myopathies.
• Numerous causative genes, primarily encoding Z-line or protein quality control proteins, have been identified.

Purpose of the Study:

• To summarize the characteristic clinical and pathological features associated with each causative gene in Myofibrillar Myopathy.
• To highlight the genetic heterogeneity and clinical variability of MFM.
• To identify the most common causes of MFM within a specific patient cohort.

Main Methods:

• Review and summarization of clinical and pathological data from MFM patients.
• Genetic analysis to identify causative mutations.
• Comparison of clinical phenotypes with identified genotypes.

Main Results:

• Several genes (DES, CRYAB, MYOT, ZASP, BAG3, FLNC, DNAJB6, FHL1, TTN, VCP) are implicated in MFM.
• Hereditary myopathy with early respiratory failure (HMERF), caused by TTN gene mutations, was unexpectedly the most frequent MFM cause in the study cohort.
• The genetic cause remains unidentified in over 60% of MFM patients.

Conclusions:

• MFM presents with variable clinical features, influenced by the specific causative gene.
• TTN mutations are a significant cause of MFM, particularly those leading to early respiratory failure.
• Further research is needed to discover novel causative genes and understand the pathomechanisms of protein aggregation in MFM.