Myasthenic Syndrome

From Anvita Health Wiki

Contents 1 More Specific Terms 2 Introduction 3 Etiology 4 Pathology 5 Genetics 6 Clinical-manifestations 7 Differential-diagnosis 8 Management 9 More General Terms 10 Additional Terms 11 Internet Database 12 References

More Specific Terms

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

Introduction

• group of inherited disorders of neuromuscular transmission

Etiology

• caused by kinetic abnormalities of the nicotinic receptor

Pathology

• small, simplified neuromuscular junctions
• normal acetylcholine receptor & acetylcholinesterase function ( DOK7 type)
• prolonged endplate currents & prolonged AChR channel opening episodes (slow-type)
• decreased activity of the AChR (fast type) by:

• slowing the rate of opening of the receptor channel
• speeding the rate of closure of the channel
• decreasing the number of openings of the channel during ACh occupancy

• failure to achieve threshold depolarization of the endplate & consequent failure to fire an action potential

Genetics

• associated with defects in DOK7 gene ( autosomal recessive)
• associated with defects in CHRNA1

• slow- channel type
• fast- channel type

• associated with defects in CHRNB1

• slow- channel type
• nicotinic receptor deficiency

• associated with defects in CHRND

• slow- channel type
• fast- channel type

• 4) associated with defects in CHRNE

• slow- channel type
• fast- channel type

• associated with defects in MUSK ( autosomal recessive)
• associated with defects in SCNA4

Clinical-manifestations

• fatigable muscle weakness
• muscle weakness affecting the axial & limb muscles

• proximal muscles effected more than distal muscles
• characteristic 'limb girdle' pattern of muscle weakness
• onset characterized by difficulty walking after normal motor milestones
• hypotonia in early-onset forms

• weakness of ocular muscles leads to ptosis & ophthalmoplegia

• ptosis often present at early age
• eye movements rarely involved in DOK7 form

• weakness in facial & bulbar musculatur affects sucking & swallowing, & leads to dysphonia
• symptoms fluctuate & worsen with physical effort

Differential-diagnosis

• limb-girdle muscular dystrophy

Management

• ephedrine may be helpful
• acetylcholinesterase inhibitors without long-term benefit#

• # distinguishing feature from limb-girdle muscular dystrophy

More General Terms

• genetic syndrome (multisystem disorder)
• muscular disease; myopathy

Additional Terms

• myasthenia gravis

Internet Database

OMIM: 601462
OMIM: 608930
OMIM: 608931
OMIM: 603967

References

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

myasthenic syndrome (congenital myasthenic syndrome, CMS)