Abstract
Muscle Specific Kinase myasthenia gravis (MuSK-MG) is an autoimmune disease that impairs neuromuscular transmission leading to generalized muscle weakness. Compared to the more common myasthenia gravis with antibodies against the acetylcholine receptor (AChR), MuSK-MG affects mainly the bulbar and respiratory muscles, with more frequent and severe myasthenic crises. Treatments are usually less effective with the need for prolonged, high doses of steroids and other immunosuppressants to control symptoms. Under physiological condition, MuSK regulates a phosphorylation cascade which is fundamental for the development and maintenance of postsynaptic AChR clusters at the neuromuscular junction (NMJ). Agrin, secreted by the motor nerve terminal into the synaptic cleft, binds to low density lipoprotein receptor-related protein 4 (LRP4) which activates MuSK. In MuSK-MG, monovalent MuSK-IgG4 autoantibodies block MuSK-LRP4 interaction preventing MuSK activation and leading to the dispersal of AChR clusters. Lower levels of divalent MuSK IgG1, 2, and 3 antibody subclasses are also present but their contribution to the pathogenesis of the disease remains controversial. This review aims to provide a detailed update on the epidemiological and clinical features of MuSK-MG, focusing on the pathophysiological mechanisms and the latest indications regarding the efficacy and safety of different treatment options.