Responsible genes | % of UK cases | Pathology | Differentiating clinical features | Treatment | |
AChR deficiency | CHRNE, CHRNA, CHRNB, CHRND | 20 | Low expression of AChR | Early onset, severe ophthalmoplegia | Pyridostigmine + 3,4-DAP |
Rapsyn deficiency | RAPSN | 15 | Deficiency of AChR clustering protein | Arthrogryposis multiplex congenita, apnoeic episodes, congenital strabismus, syndrome improves with age | Pyridostigmine + 3,4-DAP |
Dok-7 synaptopathy | DOK7 | 15 | Incomplete synaptogenesis | Congenital stridor, late appearance of motor weakness, limb girdle pattern of weakness, tongue wasting | Ephedrine or salbutamol + 3,4-DAP |
Slow channel syndrome | CHRNA, CHRNE, CHRNB, CHRND | 7 | Prolonged channel opening in response to ACh | Variable severity and age at onset, distal arm weakness predominant, moderate ophthalmoplegia, prominent muscle wasting. Autosomal dominant inheritance | Fluoxetine or quinidine |
Fast channel syndrome | CHRNA, CHRNE, CHRND | 5 | Shortened channel opening in response to ACh | Respiratory insufficiency at birth, sudden and severe crises throughout childhood, severe ophthalmoplegia | Pyridostigmine + 3,4-DAP |
Acetylcholinesterase deficiency | COLQ | 5 | Failure to anchor AChE in synaptic cleft | Axial and respiratory weakness from early infancy, slowed pupillary light response. | Ephedrine |
Choline acetyltransferase deficiency | CHAT | 2 | Failure of ACh synthesis | Apnoeic episodes in infancy, EMG decrement often only at 10 Hz stimulation | Pyridostigmine |
Other congenital myasthenic syndromes | Unknown | 30 | Unknown |
3,4-DAP, 3,4-diaminopyridine; ACh, acetylcholine; AChE, acetylcholinesterase; AChR, acetylcholine receptor.