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I. DEFINITION

Myasthenia gravis (MG) is an autoimmune disease where antibodies attack and destroy nerve muscle connections that affect neuromuscular function. MG presents with skeletal muscle weakness and progressive fatigability that increases with activity and improves with rest. MG has multiple subgroups, but 3 distinct forms are seen in children: transient neonatal MG (TNMG), juvenile MG, and congenital MG (now known as congenital myasthenic syndromes).

  1. Transient neonatal myasthenia gravis is the most common form of MG in the neonate and will be discussed here. It is seen in neonates born to mothers with active MG (most common), but it can occur in infants of mothers who are in remission. This occurs when maternal AChR antibodies passively cross from the mother through the placenta into the fetus, resulting in destruction of fetal AChRs. Only some infants born to mothers with MG develop TNMG. It is transient, and the condition only lasts a few weeks.

  2. Juvenile myasthenia gravis is rare and presents in late infancy and adolescence, typically in female, usually before 19 years of age, is not transient, has no genetic component, and has a clear autoimmune component.

  3. Congenital myasthenic syndromes are very rare causes of neuromuscular junction failure in neonates (reported incidence of approximately 600 families with affected individuals) that are not related to maternal disease. Common examples include primary AChR deficiency (MC), RAPSN mutations, DOK7 mutations, and COLQ mutations. It is almost always a permanent disorder without remission. Characteristics include a positive family history, inherited in an autosomal recessive pattern, usually manifest in infancy or early childhood with variable degrees of weakness that fluctuates, are caused by genetic defects (specific mutations) in components of the neuromuscular junction (presynaptic, synaptic, and postsynaptic), and has no autoimmune component. Weakness in the ocular and bulbar muscles typically occurs in these infants. Ptosis is more common in these infants than in infants with TNMG. Infants can have feeding difficulties, delay in crawling and walking. Note that life-threatening episodes of apnea can occur in these infants.

II. INCIDENCE

The annual incidence of MG is 8 to 10 cases per million; the prevalence is 150 to 250 cases per million. TNMG occurs in 10% to 20% of infants born to mothers with MG. There is no race or sex preference and no correlation between maternal disease severity or maternal antibody level and risk of TNMG in the neonate. Occasionally an infant with TNMG is born to a mother with asymptomatically elevated AChR antibody levels. The risk of recurrence in subsequent pregnancies is 75%.

III. PATHOPHYSIOLOGY

MG is an autoimmune disease that affects acetylcholine neurotransmission at the neuromuscular junction. Immunoglobulin G autoantibodies bind to the AChR (75%–85%), muscle-specific kinase (1%–10%), or lipoprotein receptor–related peptide 4 (1%–3%), preventing the nerve impulse from activating the muscle. Other autoantibodies may also play a role in disease severity. Antibody binding to these proteins ...

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