Walsh & Hoyt: Congenital Myasthenic Syndromes

Once thought to be a single clinical and pathologic entity, congenital MG is now known to be a heterogeneous group of genetic neuromuscular transmission disorders. These conditions can be differentiated from acquired autoimmune MG on the basis of clinical, electromyographic, electrophysiologic, cytochemical, structural, and molecular genetic grounds. Many but not all cases present neonatally or in infancy with ptosis, fluctuating ophthalmoparesis, poor feeding, and respiratory difficulty. Symptoms may be episodic or may demonstrate fatigability that is worsened by crying, activity, or fever. Persistence of symptoms, rather than a transient monophasic course, distinguishes a congenital myasthenic syndrome from neonatal MG. Some syndromes may not even present until adolescence or adulthood. Serum anti-ACh receptor antibodies are absent. In many cases, siblings or parents are affected, but a negative family history does not exclude autosomal-recessive inheritance. The edrophonium test, which relies on intact acetylcholinesterase and normal channel open times for its effect, is negative in many congenital myasthenic syndromes. Thus, a negative test does not exclude the diagnosis, and a positive test cannot distinguish any of the congenital myasthenic syndromes from autoimmune myasthenia. The diagnosis instead rests on the results of electrophysiologic testing and other key features.