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Endplate acetylcholinesterase deficiency(CMS5)

MedGen UID:
400481
Concept ID:
C1864233
Disease or Syndrome
Synonyms: CMS Ic; CMS5; COLQ-Related Congenital Myasthenic Syndrome; CONGENITAL MYASTHENIC SYNDROME TYPE Ic; ENGEL CONGENITAL MYASTHENIC SYNDROME; MYASTHENIC SYNDROME, CONGENITAL, 5; MYASTHENIC SYNDROME, CONGENITAL, ENGEL TYPE
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
 
Gene (location): COLQ (3p25.1)
OMIM®: 603034
Orphanet: ORPHA98915

Definition

Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction. Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic. Endplate acetylcholinesterase deficiency is an autosomal recessive congenital myasthenic syndrome characterized by a defect within the synapse at the neuromuscular junction (NMJ). Mutations in COLQ result in a deficiency of acetylcholinesterase (AChE), which causes prolonged synaptic currents and action potentials due to extended residence of acetylcholine in the synaptic space. Treatment with ephedrine may be beneficial; AChE inhibitors and amifampridine should be avoided (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). [from OMIM]

Additional description

From GHR
Congenital myasthenic syndrome is a group of conditions characterized by muscle weakness (myasthenia) that worsens with physical exertion. The muscle weakness typically begins in early childhood but can also appear in adolescence or adulthood. Facial muscles, including muscles that control the eyelids, muscles that move the eyes, and muscles used for chewing and swallowing, are most commonly affected. However, any of the muscles used for movement (skeletal muscles) can be affected in this condition. Due to muscle weakness, affected infants may have feeding difficulties. Development of motor skills such as crawling or walking may be delayed. The severity of the myasthenia varies greatly, with some people experiencing minor weakness and others having such severe weakness that they are unable to walk. Some individuals have episodes of breathing problems that may be triggered by fevers or infection. Severely affected individuals may also experience short pauses in breathing (apnea) that can lead to a bluish appearance of the skin or lips (cyanosis).  http://ghr.nlm.nih.gov/condition/congenital-myasthenic-syndrome

Clinical features

Ophthalmoparesis
MedGen UID:
463310
Concept ID:
C3151960
Finding
Ptosis
MedGen UID:
504471
Concept ID:
CN000475
Finding
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Dysarthria
MedGen UID:
333395
Concept ID:
C1839743
Finding
Dysphagia
MedGen UID:
342867
Concept ID:
C1853381
Finding
Prolonged miniature endplate currents
MedGen UID:
505538
Concept ID:
CN003098
Finding
An abnormal prolongation of the miniature endplate potentials, i.e. the postsynaptic response to transmitter released from an individual vesicle at the neuromuscular junction.
Decreased size of nerve terminals
MedGen UID:
505539
Concept ID:
CN003103
Finding
A reduction in the size of nerve terminals.
Fatigable weakness
MedGen UID:
500955
Concept ID:
CN003133
Finding
A type of weakness that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
Scoliosis
MedGen UID:
427922
Concept ID:
CN002409
Finding
The presence of an abnormal lateral curvature of the spine.
Hyperlordosis
MedGen UID:
505513
Concept ID:
CN002983
Finding
Abnormally increased cuvature (anterior concavity) of the lumbar or cervical spine.
Dysphagia
MedGen UID:
342867
Concept ID:
C1853381
Finding
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Weak cry
MedGen UID:
65892
Concept ID:
C0234860
Finding
Respiratory insufficiency
MedGen UID:
155440
Concept ID:
C0748358
Finding
Respiratory insufficiency due to muscle weakness
MedGen UID:
332136
Concept ID:
C1836141
Finding
Abnormality of the immune system
MedGen UID:
427926
Concept ID:
CN002465
Finding
An abnormality of the immune system.
Respiratory insufficiency due to muscle weakness
MedGen UID:
332136
Concept ID:
C1836141
Finding
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Decreased muscle mass
MedGen UID:
324803
Concept ID:
C1837466
Finding
Generalized muscle weakness
MedGen UID:
334473
Concept ID:
C1843698
Finding
Type 2 muscle fiber atrophy
MedGen UID:
355249
Concept ID:
C1864580
Finding
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
EMG: decremental response of compound muscle action potential to repetitive nerve stimulation
MedGen UID:
500950
Concept ID:
CN003071
Finding
A compound muscle action potential (CMAP) is a type of electromyography (EMG). CMAP refers to a group of almost simultaneous action potentials from several muscle fibers in the same area evoked by stimulation of the supplying motor nerve and are recorded as one multipeaked summated action potential. This abnormality refers to a greater than normal decrease in the amplitude during the course of the investigation.
Fatigable weakness
MedGen UID:
500955
Concept ID:
CN003133
Finding
A type of weakness that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
Limb muscle weakness
MedGen UID:
500963
Concept ID:
CN003336
Finding
Reduced strength and weakness of the muscles of the arms and legs.
Limb muscle weakness
MedGen UID:
500963
Concept ID:
CN003336
Finding
Reduced strength and weakness of the muscles of the arms and legs.

Recent clinical studies

Etiology

Liewluck T, Selcen D, Engel AG
Muscle Nerve 2011 Nov;44(5):789-94. Epub 2011 Sep 23 doi: 10.1002/mus.22176. [Epub ahead of print] PMID: 21952943Free PMC Article

Diagnosis

Chan SH, Wong VC, Engel AG
Pediatr Neurol 2012 Aug;47(2):137-40. doi: 10.1016/j.pediatrneurol.2012.04.022. PMID: 22759693Free PMC Article
Bestue-Cardiel M, Sáenz de Cabezón-Alvarez A, Capablo-Liesa JL, López-Pisón J, Peña-Segura JL, Martin-Martinez J, Engel AG
Neurology 2005 Jul 12;65(1):144-6. doi: 10.1212/01.wnl.0000167132.35865.31. PMID: 16009904

Therapy

Chan SH, Wong VC, Engel AG
Pediatr Neurol 2012 Aug;47(2):137-40. doi: 10.1016/j.pediatrneurol.2012.04.022. PMID: 22759693Free PMC Article
Liewluck T, Selcen D, Engel AG
Muscle Nerve 2011 Nov;44(5):789-94. Epub 2011 Sep 23 doi: 10.1002/mus.22176. [Epub ahead of print] PMID: 21952943Free PMC Article
Bestue-Cardiel M, Sáenz de Cabezón-Alvarez A, Capablo-Liesa JL, López-Pisón J, Peña-Segura JL, Martin-Martinez J, Engel AG
Neurology 2005 Jul 12;65(1):144-6. doi: 10.1212/01.wnl.0000167132.35865.31. PMID: 16009904
Breningstall GN, Kurachek SC, Fugate JH, Engel AG
J Child Neurol 1996 Jul;11(4):345-6. PMID: 8807428

Clinical prediction guides

Liewluck T, Selcen D, Engel AG
Muscle Nerve 2011 Nov;44(5):789-94. Epub 2011 Sep 23 doi: 10.1002/mus.22176. [Epub ahead of print] PMID: 21952943Free PMC Article
Stum M, Girard E, Bangratz M, Bernard V, Herbin M, Vignaud A, Ferry A, Davoine CS, Echaniz-Laguna A, René F, Marcel C, Molgó J, Fontaine B, Krejci E, Nicole S
Hum Mol Genet 2008 Oct 15;17(20):3166-79. Epub 2008 Jul 21 doi: 10.1093/hmg/ddn213. [Epub ahead of print] PMID: 18647752
Hutchinson DO, Walls TJ, Nakano S, Camp S, Taylor P, Harper CM, Groover RV, Peterson HA, Jamieson DG, Engel AG
Brain 1993 Jun;116 ( Pt 3):633-53. PMID: 8390325

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