Myasthenia gravis (MG) is a rare, clinically heterogeneous, autoimmune disorder of the neuromuscular junction characterized by fatigable weakness of voluntary muscles.
The prevalence is estimated to be 1/5,000 and the incidence 1/250,000 to 1/33,000 in Europe. MG affects both males and females: mainly females before the age of 40 years and equally males and females after 50 years of age.
Myasthenia gravis can develop at any age but there is a bimodal peak in age of onset in the adult-onset form, with primarily female patients before 40 years of age, and primarily males after 50 years of age (Adult-onset myasthenia gravis; see this term). Patients have fluctuating weakness worsening with repetitive activities, heat, stress improving with rest with involvement skeletal muscle groups of ocular, bulbar, extremities and neck. Ocular manifestations include fluctuating diplopia and ptosis. Bulbar involvement may be found with fatigable chewing, dysphagia and dysarthria and some patients develop generalized muscle weakness, which may become serious with respiratory muscle weakness. In the juvenile form, onset is before 18 years of age (juvenile myasthenia gravis; see this term) and patients also present ocular and possibly generalized muscle weakness. A transient neonatal form causing hypotonia and feeding difficulties occurs in some newborns born to mothers with MG (transient neonatal myasthenia gravis; see this term). Congenital genetic forms of MG with a different pathogenesis also occur (congenital myasthenic syndromes, see this term).
The exact pathogenesis is not known but MG is related to circulating antibodies to various muscle receptors, including acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK). Another target, the low density lipoprotein receptor-related protein 4 (LRP4), has been also described. The thymus is thought to trigger antibody production in the form with anti-AChR antibodies. These antibodies have been found to play a pathogenic role in all the forms of the disease. The disorder can also be drug induced (D-penicillamine, interferon alpha, and bone marrow transplantation). An initial infection (EBV) may be responsible for some cases of MG. The role of infections has been strongly suggested by evidence of involvement of interferon type I in the disease, but direct evidence is lacking.
Last update: November 2014
- Dr Sonia BERRIH-AKNIN
- Pr Bruno EYMARD