Walsh & Hoyt: Presynaptic Congenital Myasthenic Syndromes

These disorders were previously called ""familial infantile myasthenia."" In 1979, however, Hart et al. described an autosomal-recessive congenital myasthenic disorder in two siblings. An 18-year-old boy and his 5-year-old sister had fluctuating ptosis since birth, feeding difficulties during infancy, easy fatigability on exertion, and episodic apnea following crying, vomiting, or febrile illnesses. Symptoms responded to neostigmine but not to prednisone and improved with age. No circulating anti-ACh receptor antibody was found in either child. Repetitive nerve stimulation in the older child showed decremental responses during 2-Hz stimulation after exercise. Subsequent cases were described by Mora et al., who found that the size of synaptic vesicles was reduced in some patients. The defective step or steps in ACh synthesis are unknown but could involve choline reuptake, ACh assembly via choline acetyltransferase, or vesicle packaging. A related autosomalrecessive presynaptic syndrome marked by less episodic symptoms is associated with a paucity of synaptic vesicles and reduced quantal release.