An estimated 10 to 20 percent of babies born to mothers with myasthenia show transient signs of myasthenia (hypotonia, weak cry, and suck). This transitory phenomenon is apparent at birth and has a mean duration of about 2 to 5 weeks; recovery is usually complete within 2 months of birth (rarely longer), without later relapse. Uncommonly, the mother with myasthenia reports reduced intrauterine movements, suggesting a dangerous degree of myasthenia in the fetus. A few of these children will be born with arthrogryposis, the result of a sustained period of intrauterine immobility, and this complication tends to recur in subsequent births.
It has long been assumed that neonatal myasthenia is a result of the passive transplacental transfer of AChR antibodies. This explanation is not entirely satisfactory insofar as maternal AChR antibodies are transferred from mother to fetus in all AChR antibody-positive pregnancies and the incidence and severity of neonatal myasthenia gravis do not correlate with the severity or duration of the mother’s illness or with the serum level of the maternal AChR antibody. In fact, neonatal myasthenia may occur when the mother is in remission.
Administration of plasma exchange and anticholinesterase drugs to the infant may be useful in hastening recovery from neonatal myasthenia.
Sporadically in the medical literature, there have appeared reports of a benign congenital myopathy in which myasthenic features could be recognized in the neonatal period or soon thereafter. The affected infants had been born to mothers who did not have myasthenia and were in the past described under headings such as “Myasthenia Gravis in the Newborn” and “Familial Infantile Myasthenia” (Greer and Schotland; Robertson et al) to distinguish the condition from passively transmitted neonatal myasthenia.
In the 1970s and 1980s, after the autoimmune basis of myasthenia gravis was established and its morphologic and physiologic features defined, the differences between this disease and the familial infantile forms became evident. Since then, at least 8 distinct and rare congenital myasthenic syndromes have been delineated on the basis of their electrophysiologic and ultrastructural features, and a number of others have been partially characterized.
As indicated in Table 46-3, the congenital myasthenic syndromes are inherited defects in components of the presynaptic, synaptic, or postsynaptic junctional apparatus. Broadly speaking, the defects involve resynthesis or packaging of ACh or a paucity of synaptic vesicles (presynaptic); deficient quantal release; a deficiency of endplate ACh esterase (synaptic); or kinetic abnormalities in the AChR channels, or AChR deficiency (postsynaptic). It has been estimated that in three-fourths of the cases, the defect is postsynaptic.
These disorders are distinguished by neonatal onset, fluctuating and sometimes progressive weakness that may be quite severe, sometimes pronounced muscle hypotrophy, persistent ptosis, and seronegativity for anti-AChR and anti-MuSK antibodies. Moreover, heritability (typically autosomal recessive) is suggested by familial occurrence of the disorders among siblings. The most important clue to the disease in the neonate is an increase in ptosis and in bulbar and respiratory weakness with crying. Later in infancy these symptoms, as well as fluctuating ocular palsies and abnormal fatigability, are brought out by other types of sustained activities. Motor milestones may be delayed. In some cases, the myasthenic weakness and fatigability do not become evident until the second and third decades of life. Testing with anticholinesterase drugs is inconsistently positive in a few forms of congenital myasthenia as mentioned further on, but it usually is negative.