Myasthenia gravis and other neuromuscular junction disorders

Abstract

Myasthenia gravis is the most common autoimmune disease affecting the neuromuscular junction and is characterised by painless fatigable muscle weakness. It is caused by autoantibodies against neuromuscular junction proteins, either the nicotinic acetylcholine receptor (AChR) or the muscle specific tyrosine kinase (MuSK). Mutations in neuromuscular junction proteins cause congenital myasthenic syndromes. Other antibody mediated conditions affecting the neuromuscular junction include Lambert Eaton myasthenic syndrome and neuromyotonia. Figure 1 The neuromuscular junction and the proteins involved in neuromuscular transmission. Several of the proteins at the neuromuscular junction are targets for autoimmune disorders (AChR and MuSK in myasthenia gravis, VGCC in Lambert–Eaton myasthenic syndrome and VGKC in neuromyotonia). Genetic mutations can affect several of these proteins (AChR, Rapysn, MuSK, Dok-7, etc) causing congenital myasthenic syndromes. ACh, acetylcholine; AChE, acetylcholinesterase; AChR, acetylcholine receptor; MuSK, muscle specific tyrosine kinase; VGCC, voltage gated calcium channel; VGKC, voltage gated potassium channel; VGSC voltage gated sodium channel.