Myofibrillar Myopathies include a group of neuromuscular disorders, all characterized by structural changes in the myofibril, resulting from intracellular accumulation of proteins such as desmins. This group of diseases is both clinically and genetically heterogeneous and the genetic basis of its pathology has only been elucidated in about 20% of cases. Desmin Related Myopathy (DRM) is one of the better understood myopathies. As in all myopathies, the condition is characterized by progressive weakness involving predominantly the distal muscles. Some affected individuals may also experience sensory symptoms, muscular atrophy, and cramps. Electrical irritability can be seen in the EMG profile. About 15-30% of affected individuals show overt cardiomyopathy, in the form of arrhythmia, conduction defects, or even congestive heart failure.

Diagnosis of the MFMs is based on clinical findings, results of EMG and nerve conduction studies, as well as muscle biopsies. Muscle biopsies are expected to show atrophic muscle fibers, muscle splitting, and abnormal intracellular protein inclusions. Differential diagnoses include other distal myopathies, such as Myotonic Dystrophy, and motor and sensory neuropathies, such as inclusion body myopathy, and dysferlinopathy. Treatment at present is only supportive in nature. Patients with severe cardiac conduction defects and/or arrhythmias are advised to use pacemakers or implantable cardioverter defibrillator. Physical therapy is recommended for those at an advanced stage of muscle weakness.

The underlying pathogenesis of all MFMs is the disintegration of the myofibrillar network beginning at the Z-disk. Desmin Related MFM is caused by defects in the Desmin protein, due to mutations in the Desmin gene. In its normal form, the desmin protein is located at the periphery of the Z-disk, where it interconnects the entire contractile apparatus with the cytoskeleton, nuclei, and other cellular organelles. The defective desmin protein is unable to form filaments, and instead aggregates throughout the cell, disrupting the filamentous network. Up to date, more than 20 mutations have been identified in the desmin gene.

Both autosomal dominant and recessive forms of the condition are seen. The recessive form is the more severe type, with an earlier onset, while the dominant form is less severe and shows a later onset.