Slow-Channel Congenital Myasthenic Syndrome

Abstract

Congenital myasthenic syndromes are a group of genetically heterogeneous disorders of the neuromuscular junction that can be classified by the site of the transmission defect: presynaptic, synaptic, and postsynaptic. The slow-channel syndrome is a postsynaptic congenital myasthenic syndrome, which was first described by Engel et al. in 1982, and can be caused by mutation in the genes encoding alpha, beta, delta, or epsilon (CHRNE) subunits of the acetylcholine receptor (AChR) (Table 44.1). The phenotype is characterized by dominant inheritance; selective weakness of cervical, scapular, and finger extensors and other distal muscles; and mild ophthalmoparesis. Some slow-channel syndromes cause severe disability by the end of the first decade; others present later in life and progress gradually with forearm weakness and decreased bulk of shoulder muscles. Most patients show severe involvement of cervical, wrist, and extensor muscles. While weakness and fatigability are progressive, in a few cases responses to ephedrine and salbutamol have been beneficial.