Contents

Search

myasthenic syndrome (congenital myasthenic syndrome, CMS)

group of inherited disorders of neuromuscular transmission Etiology: - caused by kinetic abnormalities of the nicotinic receptor Pathology: 1) small, simplified neuromuscular junctions 2) normal acetylcholine receptor & acetylcholinesterase function (DOK7 type) 3) prolonged endplate currents & prolonged AChR channel opening episodes (slow-type) 4) decreased activity of the AChR (fast type) by: a) slowing the rate of opening of the receptor channel b) speeding the rate of closure of the channel c) decreasing the number of openings of the channel during ACh occupancy 5) failure to achieve threshold depolarization of the endplate & consequent failure to fire an action potential Genetics: 1) associated with defects in DOK7 gene (autosomal recessive) 2) associated with defects in CHRNA1 a) slow-channel type b) fast-channel type 3) associated with defects in CHRNB1 a) slow-channel type b) nicotinic receptor deficiency 4) associated with defects in CHRND a) slow-channel type b) fast-channel type 5) 4) associated with defects in CHRNE a) slow-channel type b) fast-channel type 6) associated with defects in MUSK (autosomal recessive) 7) associated with defects in SCNA4 Clinical manifestations: 1) fatigable muscle weakness 2) muscle weakness affecting the axial & limb muscles a) proximal muscles effected more than distal muscles b) characteristic 'limb girdle' pattern of muscle weakness c) onset characterized by difficulty walking after normal motor milestones d) hypotonia in early-onset forms 3) weakness of ocular muscles leads to ptosis & ophthalmoplegia a) ptosis often present at early age b) eye movements rarely involved in DOK7 form 4) weakness in facial & bulbar musculatur affects sucking & swallowing, & leads to dysphonia 5) symptoms fluctuate & worsen with physical effort Differential diagnosis: limb-girdle muscular dystrophy Management: 1) ephedrine may be helpful 2) acetylcholinesterase inhibitors without long-term benefit# # distinguishing feature from limb-girdle muscular dystrophy

Related

myasthenia gravis

Specific

congenital myasthenic syndrome with acetylcholine receptor (nAChR) deficiency (ACHRDCMS) end-plate acetylcholinesterase deficiency (congenital myasthenic syndrome type 1C)

General

genetic syndrome (multisystem disorder) muscular disease; myopathy

Database Correlations

OMIM correlations MORBIDMAP 603967

References

  1. UniProt :accession Q18PE1
  2. Palace J et al, Clinical features of the DOK7 neuromuscular synaptopathy Brain 2007, 130:1507 PMID: 17452375