Diagnosis

Defect in NMJ

Gene

Clinical features

Treatment

Pre-synaptic defect

Choline acetyl transferase (Chat) deficiency

Failure of ACh re-synthesis or packaging

CHAT

Recurrent apnoeic spells

Impaired pupillary responses

Refractory to cholinesterase inhibitors

Synaptic

End plate acetylcholinesterase deficiency

Failure to anchor AChE in synaptic cleft

COLQ

Recurrent apnoeic episodes from infancy

Variable myasthenic symptoms between attacks. Axial weakness

Reduced active signal transmission

Cholinesterase inhibitors or 3–4 DAP

Ephedrine

Post-synaptic defect

AChR deficiency

AChR mutation

Reduced number of end plate receptors. Non functioning ε subunit replaced by foetal γ

CHRNE

CHRNA

CHRNB

CHRND

Neonatal onset. Severe ophthalmoplegia, ptosis & feeding difficulties. Mild bulbar or respiratory involvement

Generalised weakness

Reduced active signal transmission

Cholinesterase inhibitors or 3–4 DAP

AChR kinetic abnormality

Slow channel

Prolonged ion channel activation in response to ACh

CHRNE

CHRNA

CHRNB

CHRND

Variable age of onset. Autosomal Dominant

Cervical weakness with mild bulbar or respiratory involvement. Weakness and wasting in extensor and distal muscles due to endplate myopathy caused by prolonged channel activation (depolarizing block)