112: Myasthenia Gravis (Transient Neonatal)

I. DEFINITION

Myasthenia gravis is a neuromuscular disorder affecting synaptic transmission at the motor end plate. It is characterized by abnormal muscle fatigability and can be either genetic or acquired. Infants born with the genetic form of the disease (very rare) are born to healthy mothers and suffer permanent disability. Transient neonatal myasthenia gravis (TNMG) is an acquired form of the disease that occurs only in infants born to mothers with myasthenia gravis and is the predominant type and is discussed here.

II. INCIDENCE

The incidence of myasthenia gravis varies from 9 to 21 cases per million. TNMG is a rare disorder affecting 10–15% of infants born to mothers with myasthenia gravis. There is no race or sex preference. There is no correlation between disease severity in the mother and the clinical outcome of the infant. The risk of disease in a sibling is significantly higher than that of a first born.

III. PATHOPHYSIOLOGY

1. Anti-acetylcholine receptor antibodies. A total of 75–80% of mothers with myasthenia gravis have anti-acetylcholine receptor (anti-AChR) antibodies. These antibodies cause nicotinic acetylcholine receptor loss by accelerating their degradation, blocking acetylcholine binding, and inducing the lysis of the postsynaptic membrane through induction of the complement system. TNMG is caused by the passive transfer of these maternal antibodies to the fetus. The antibodies can be directed against the fetal acetylcholine receptor (present until 33 weeks' gestation) or the adult receptor. Higher maternal antibody titers directed against the fetal versus the adult acetylcholine receptor has been shown to increase the risk and severity of TNMG.

2. Anti–muscle-specific kinase antibodies. Although anti-AChR antibody–mediated TNMG is the most common cause of the disease, there have been case reports of infants developing TNMG as a result of anti–muscle-specific kinase (anti-MuSK) antibodies. There is some suggestion that this form of TNMG may be more difficult to treat with anticholinesterase agents.

IV. RISK FACTORS

See Sections II and III.

V. CLINICAL PRESENTATION

1. Antenatal. Although rare, neonatal weakness can present in utero, and mothers may comment on reduced fetal movements. Polyhydramnios can be present as a result of poor fetal swallowing. Arthrogryposis multiplex congenita can also rarely occur as a result of decreased fetal movement.

2. Postnatal. In 67% of patients symptoms are present within a few hours after birth, and 78% of patients will have symptoms within 24 hours of life. Infants whose mothers have been taking anticholinesterase agents tend to present later than infants whose mothers have not been treated. There have been no known cases with symptoms presenting after day 3 of life.

   The majority of patients present with hypotonia and inadequate suck. Many will have a weak cry, facial diparesis, lack of facial expression, feeding difficulties, and mild respiratory distress. Ptosis and ophthalmoparesis can be present although this is less common. Deep ...