Easy fatigability and weakness of muscles are the salient clinical features of disorders that affect the neuromuscular junction (NMJ). Congenital myasthenic syndromes (CMSs) are a heterogeneous group of inherited diseases of the NMJ, and each individual condition is seen infrequently. However, as a group, the incidence of these conditions is frequent enough that they should be considered in the differential diagnosis of patients who present with myasthenic symptoms, especially when the onset is from infancy or childhood.
The congenital myasthenic syndromes result from inherited disorders of the structure and/or function of the pre- and postsynaptic structures. The symptoms of fatigue and weakness result from compromise of the safety factor in neuromuscular transmission. We review the physiological basis of the safety factor of neuromuscular transmission and the clinical features, electrodiagnostic findings, diagnosis, and treatment of the common congenital myasthenic syndromes. Weakness of ocular and facial muscles beginning from infancy and childhood is the most common clinical presentation.
Repetitive nerve stimulation studies and single-fiber electromyography demonstrate abnormalities that are consistent with dysfunction of the NMJ. The advances in molecular biology, microelectrode recordings, and ultrastructural studies have elucidated the genetic basis of most of these syndromes and their pathophysiology.
Anticholinesterase agents, such as pyridostigmine, help to improve the symptoms in patients who have defects in acetylcholine resynthesis or packaging or myasthenic syndromes secondary to deficiency of acetylcholine receptors. Patients who have slow channel syndrome respond to guanidine.
Understanding of the molecular genetics and pathogenesis of congenital myasthenic syndromes have led to improved accuracy in diagnosis of and therapy for these disorders.
(THE NEUROLOGIST 6:186-196, 2000)