Clinical Manifestations

Three clinical varieties are distinguished in childhood: juvenile myasthenia gravis in late infancy and childhood, congenital myasthenia, and transient neonatal myasthenia. In the juvenile form, ptosis and some degree of extraocular muscle weakness are the earliest and most constant signs. Older children might complain of diplopia, and young children might hold open their eyes with their fingers or thumbs if the ptosis is severe enough to obstruct vision. The pupillary responses to light are preserved. Dysphagia and facial weakness are also common, and in early infancy, feeding difficulties are often the cardinal sign of myasthenia. Poor head control because of weakness of the neck flexors is also prominent. Involvement may be limited to bulbar-innervated muscles, but the disease is systemic and weakness involves limb-girdle muscles and distal muscles of the hands in most cases. Fasciculations of muscle, myalgias, and sensory symptoms do not occur. Tendon stretch reflexes may be diminished but rarely are lost.

Rapid fatigue of muscles is a characteristic feature of myasthenia gravis that distinguishes it from most other neuromuscular diseases. Ptosis increases progressively as patients are asked to sustain an upward gaze for 30-90 sec. Holding the head up from the surface of the examining table while lying supine is very difficult, and gravity cannot be overcome for more than a few seconds. Repetitive opening and closing of the fists produces rapid fatigue of hand muscles, and patients cannot elevate their arms for more than 1-2 min because of fatigue of the deltoids. Patients are more symptomatic late in the day or when tired. Dysphagia can interfere with eating, and the muscles of the jaw soon tire when an affected child chews.

Left untreated, myasthenia gravis is usually progressive and can become life threatening because of respiratory muscle involvement and the risk of aspiration, particularly at times when the child is otherwise unwell with an upper respiratory tract infection. Familial myasthenia gravis usually is not progressive.

Infants born to myasthenic mothers can have respiratory insufficiency, inability to suck or swallow, and generalized hypotonia and weakness. They might show little spontaneous motor activity for several days to weeks. Some require ventilatory support and feeding by gavage during this period. After the abnormal antibodies disappear from the blood and muscle tissue, these infants regain normal strength and are not at increased risk of developing myasthenia gravis in later childhood.

The syndrome of transient neonatal myasthenia gravis is to be distinguished from a rare and often hereditary congenital myasthenia gravis not related to maternal myasthenia that is nearly always a permanent disorder without spontaneous remission (see Table 604-1). Several distinct genetic forms are recognized, all with onset at birth or in early infancy with hypotonia, ophthalmoplegia, ptosis, dysphagia, weak cry, facial weakness, easy muscle fatigue generally, and sometimes respiratory insufficiency or failure, the last often precipitated by a minor respiratory infection. Cholinesterase inhibitors have a favorable effect in most, but in some forms the symptoms and signs are actually worsened. Most congenital myasthenic syndromes are transmitted as autosomal recessive traits, but the slow channel syndrome is autosomal dominant. Five defective postsynaptic molecules have been identified in the pathogenesis of congenital myasthenia gravis and account for 85% of cases; rapsyn may be the most common. Acetylcholine receptor deficiencies have >60 identified genetic mutations. Anti-AChR and anti-MuSK antibodies are absent in serum, unlike autoimmune forms of myasthenia gravis affecting older children and adults.

Three presynaptic congenital myasthenic syndromes are recognized, all as autosomal recessive traits; some of these have anti-MuSK antibodies. These children exhibit weakness of extraocular, pharyngeal, and respiratory muscles and later show shoulder girdle weakness as well. Episodic apnea is a problem in congenital myasthenia gravis. Another synaptic form is caused by absence or marked deficiency of motor endplate AChE in the synaptic basal lamina, and postsynaptic forms of congenital myasthenia are caused by mutations in ACh receptor subunit genes that alter the synaptic response to ACh. An abnormality of the ACh receptor channels appearing as high conductance and excessively fast closure may be the result of a point mutation in a subunit of the receptor affecting a single amino acid residue. Children with congenital myasthenia gravis do not experience myasthenic crises and rarely exhibit elevations of anti-ACh antibodies in plasma.

Myasthenia gravis is occasionally associated with hypothyroidism, usually due to Hashimoto thyroiditis. Other collagen vascular diseases may also be associated. Thymomas, noted in some adults, rarely coexist with myasthenia gravis in children, nor do carcinomas of the lung occur, which produce a unique form of myasthenia in adults called Eaton-Lambert syndrome. Postinfectious myasthenia gravis in children is transitory and usually follows a varicella-zoster infection by 2-5 wk as an immune response.