Congenital Myasthenic Syndromes

Diseases,

Classification:

Presynaptic:

  • Choline Acetyltransferase

Synaptic:

  • Endplate acetylcholinesterase AChE deficiency

Postsynaptic:

  • AChR deficiencies
  • AChR kinetic abnormalities (slow & fast channel syndromes)
  • Rapsyn mutation

Diagnosis:

In general:

  • AChR antibodies: negative
  • Genetic testing confirms the diagnosis
Clinical features:

At birth or <2 y.o.:

  • Respiratory and feeding difficulties
  • Ocular symptoms (ptosis impaired movements)

NCS/EMG:

  • RNST: decrement in amplitude CMAP
  • Single fibre EMG: increased jitter +transmssion blocking
  • Single supramaximal stimulus: repetitive motor evoked responses
Genetics:

Autosomal dominant, autosomal recessive

AChR Slow channel syndrome:

Clinical features:

  • Limb weakness, spares ocular and oropharynx

Genetics:

  • AChR mutations: 56 mutations, alpha, beta, epsilon subunits

Electrophysiology, NCS/EMG:

  • Repetition CMAP: second peak (after potential)
AChR fast channel syndrome:

Response to ACh is reduced (lower affinity)
Activation episodes are short in duration

Rapsyn mutation:

RAPSN gene, chr. 11p11.2-p11.1. Rapsyn protein.

Dok-7 mutations:

Autosomal recessive
DOK7 gene Chr. 4, Dok-7 protein

Related articles: