Lorenzoni_2012_Pediatr.Neurol_46_141

Congenital myasthenic syndromes comprise heterogeneous genetic diseases characterized by compromised neuromuscular transmission. Congenital myasthenic syndromes are classified as presynaptic, synaptic, or postsynaptic, depending on the primary defect's location within the neuromuscular junction. Presynaptic forms are the rarest, affecting an estimated 7-8% of patients; synaptic forms account for approximately 14-15% of patients; and the remaining 75-80% are attributable to postsynaptic defects. Clinical manifestations vary by congenital myasthenic syndrome subtype. Electrophysiologic, morphologic, and molecular descriptions of various forms of congenital myasthenic syndromes have led to an enhanced understanding of clinical manifestations and disease pathophysiology. Although congenital myasthenic syndromes are indicated by clinical manifestations, family history, electrophysiologic studies, and responses to acetylcholinesterase inhibitors, overlap in some presentations occurs. Therefore, genetic testing may be necessary to identify specific mutations in CHAT, COLQ, LAMB2, CHRNA, CHRNB, CHRND, CHRNE, CHRNG, RAPSN, DOK7, MUSK, AGRN, SCN4A, GFPT1, or PLEC1 genes. The identification of congenital myasthenic syndromes subtypes will prove important in the treatment of these patients. Different drugs may be beneficial, or should be avoided because they are ineffective or worsen some forms of congenital myasthenic syndromes. We explore the classification, clinical manifestations, electrophysiologic features, genetics, and treatment responses of each congenital myasthenic syndrome subtype.