Myopathies Associated With Monoclonal Gammopathies of Clinical Significance: A Narrative Review

Monoclonal gammopathies of clinical significance (MGCS)-associated myopathies are rare diseases in which the monoclonal protein (M-protein) causes significant muscle damage. The pathophysiology of MGCS-associated myopathies remains unclear. A toxic M-protein may cause muscle degradation directly through deposition of its light and/or heavy chains in the muscle or indirectly via complex dysregulation of the immune system. Among the MGCS-associated myopathies, amyloid light chain (AL) amyloidosis-associated myopathy and sporadic late-onset nemaline myopathy with monoclonal gammopathy (SLONM-MG) are recognized. However, non-amyloid light chain deposition disease (LCDD)-associated myopathy and the recently described MGCS-associated glycogen storage myopathy (GSM) are also rare entities belonging to the array of MGCS-associated myopathies. In AL amyloidosis-associated myopathy and non-amyloid LCDD-associated myopathy, the muscle involvement usually occurs in the context of a broader systemic disease. Whereas, in SLONM-MG and MGCS-GSM, no systemic involvement occurs outside the muscle (skeletal and cardiac muscle). The confirmation of these myopathies relies on distinctive pathological features in muscle biopsy studies. Since these acquired myopathies are linked to MGCS, many authors consider that chemotherapy is the best therapeutic approach to manage these myopathies. Despite their severity, an early and accurate diagnosis is crucial due to the treatability of MGCS-associated myopathies.