This document describes several subtypes of congenital myasthenic syndromes (CMS), including their clinical features, electrophysiological features, response to acetylcholinesterase inhibitors, and recommended treatments. The subtypes include: 1) paucity of acetylcholine release, 2) primary acetylcholine receptor deficiency, 3) acetylcholinesterase deficiency, 4) abnormal clustering/function of the acetylcholine receptor due to various genetic factors like LRP4, DOK7, rapsyn, agrin, MuSK, 5) limb girdle CMS, and 6) congenital myasthenic dystrophy with myasthenia gravis. Each subtype is characterized by specific clinical presentations

33. Subtype Clinical features Electrophysiologic
features
Response to AChE
inhibitors
Treatment
Paucity of ACh release
 Respiratory failure
at birth
 Episodic apnea
 Improve with age
Decremental
response to
RNS
improve
 AChE inhibitor,
 3,4 DAP
1ry AChR deficiency
 Variable severity
 Ptosis
 EOMs and limb
fatigue
AChR kinetic disorder: fast channel
syndrome
 AChE inhibitor,
 3,4 DAP(caution)

34. Subtype Clinical features Electrophysiologic
features
Response to AChE
inhibitors
Treatment
AChE deficiency  Axial weakness,
scoliosis
 Apnea
 ±EOM
 Pupillary response:
slow
 After discharge on
nerve stimulation
 Decremental
response to RNS
worsen
 Albuterol
 Ephedrine
 3,3 DAP
 Avoid AChE
inhibitors
AChR kinetic disorder: slow
channel syndrome
 Weak extensors of
neck Ms and forearm
Ms
 Respiratory Ms
weakness
• Fluoxetine and
quinidine
• Avoid AChE
inhibitors
Abnormal clustering/function of
AChR, due to LRP4 gene
 Congenital onset
 Respiratory failure
 Hypotonia
 EOMs weakness
Decremental
response to RNS
Avoid AChE
inhibitors

35. Subtype Clinical features Electrophysiologic
features
Response to ache
inhibitors
Treatment
Abnormal
clustering/function of AChR,
due to DOK7
Limb girdle weakness
Ptosis
No EOMs
Decremental
response to
RNS
variable
Albuterol
Ephedrine
AChE inhibitors(may worsen)
Abnormal
clustering/function of AChR,
due to Rapsyn
Hypotonia
Respiratory failure
Arthrogryposis
Albuterol
Abnormal
clustering/function of AChR,
due to agrin
Limb girdle or distal
weakness
Apnea
Albuterol
AChE inhibitors(may worsen)
Abnormal
clustering/function of AChR,
due to MuSK
Congenital ptosis
EOM and Limb girdle
weakness
Albuterol
? AChE inhibitors and 3,4 DAP
Limb girdle CMS Limb girdle weakness
No ptosis or EOM
Albuterol
Ephedrine
? AChE inhibitors and 3,4 DAP
Congenital Ms dystrophy
with MG
Generalized weakness
Ptosis and EOM
Elevated CK
No response to AChE inhibitors
or 3,4 DAP