Description

A disorder of neuromuscular transmission characterized by fluctuating muscle weakness:

• Ocular myasthenia gravis (MG) (15%): weakness limited to eyelids and extraocular muscles
• Generalized MG (85%): commonly affects ocular as well as a variable combination of bulbar, proximal limb, and respiratory muscles
• 50% of patients who present with ocular symptoms develop generalized MG within 2 years.
• Onset may be sudden and severe, but it is typically mild and intermittent over many years, maximum severity reached within 3 years for 85%.
• System(s) affected: neurologic, hematologic, lymphatic, immunologic, musculoskeletal

Epidemiology

Occurs at any age but a bimodal distribution to the age of onset:

• Female: 20 to 40 years old
• Male: 60 to 80 years old

Prevalence
In the United States, 70 to 320/1 million; increasing over the past 5 decades

Pediatric Considerations
A transient form of neonatal MG seen in 10–20% of infants born to mothers with MG; it occurs as a result of the transplacental passage of maternal antibodies that interfere with function of the neuromuscular junction; resolves in weeks to months; autoimmune juvenile MG makes up 10–15% of cases of MG in North America.

Etiology and Pathophysiology

An autoimmune disorder resulting in the reduction in the function of acetylcholine receptors (AChRs) at muscle end plates, resulting in insufficient neuromuscular transmission

• Seropositive/acetylcholine receptor (anti-AChR): a humoral, antibody-mediated, T-cell–dependent attack of the AChRs or receptor-associated proteins at the postsynaptic membrane of the neuromuscular junction; found in 85% of generalized MG and 50% of ocular MG; thymic abnormalities common (1)
• Muscle-specific kinase (MuSKs): 5% of generalized MG patients; typically females; is a severe form, respiratory and bulbar muscles involved; thymic abnormalities are rare (1).
• In remainder of seronegative, 12–50% with anti-LRP4, a molecule that forms a complex with MuSK, mild generalized weakness most common (1)
• Seronegative MG (SNMG): 5%; may have anti-AChR detectable by cell-based assay; clinically similar to anti-AChR; thymic hyperplasia may be present (1).
• Also documented immediately after viral infections (measles, Epstein-Barr virus [EBV], HIV, and human T-lymphotropic virus [HTLV])

Genetics
Familial predisposition is seen in 5% of cases.

Risk Factors

• Familial MG
• D-penicillamine (drug-induced MG)
• Other autoimmune diseases

Commonly Associated Conditions

• Thymic hyperplasia (60–70%)
• Thymoma (10–15%)
• Autoimmune thyroid disease (3–8%)