Myopathies with Myofibrillar Pathology

Myofibrillar pathology refers to a series of muscle histopathological abnormalities resulting from myofibrillar dissolution beginning at the Z-discs, leading to accumulation of myofibrillar degradation products and multiple ectopic sarcoplasmic proteins aggregates. Myopathies with myofibrillar pathology (myofibrillar myopathies, MFM) are clinically and genetically heterogeneous. They can manifest with proximal, distal, axial or scapuloperoneal phenotype. Cardiac and respiratory muscle involvement is common. A peripheral neuropathy can accompany the myopathy in a small proportion of patients. Over the years, several genes causative of myopathy with myofibrillar pathology have been discovered. Most proteins encoded by these causative genes are structural and non-structural proteins located at the Z-disc or associated with the Z-disc. This chapter provides an overview on myopathies manifesting with myofibrillar pathology, outlines the overlapping as well as unique clinical and pathological features of each disorder, and discusses the known molecular pathomechanisms related to each defective protein leading to the shared myofibrillar degeneration.