Format

Send to:

Choose Destination

Endplate acetylcholinesterase deficiency(CMS5)

MedGen UID:
400481
Concept ID:
C1864233
Disease or Syndrome
Synonyms: CMS5; COLQ-Related Congenital Myasthenic Syndrome; MYASTHENIC SYNDROME, CONGENITAL, 5
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
 
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).  https://ghr.nlm.nih.gov/condition/congenital-myasthenic-syndrome

Clinical features

Ptosis of eyelid
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
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).
Ophthalmoparesis
MedGen UID:
155551
Concept ID:
C0751401
Sign or Symptom
Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement.
Weakness of limb
MedGen UID:
107956
Concept ID:
C0587246
Finding
Reduced strength and weakness of the muscles of the arms and legs.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Decreased size of nerve terminals
MedGen UID:
505539
Concept ID:
CN003103
Finding
A reduction in the size of nerve terminals.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
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.
Weakness of limb
MedGen UID:
107956
Concept ID:
C0587246
Finding
Reduced strength and weakness of the muscles of the arms and legs.
Generalized muscle weakness
MedGen UID:
155433
Concept ID:
C0746674
Sign or Symptom
Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature.
Fatigable weakness
MedGen UID:
451076
Concept ID:
C0947912
Disease or Syndrome
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.
Decreased muscle mass
MedGen UID:
373256
Concept ID:
C1837108
Finding
Type 2 muscle fiber atrophy
MedGen UID:
355249
Concept ID:
C1864580
Finding
Atrophy (wasting) affecting primary type 2 muscle fibers. This feature in general can only be observed on muscle biopsy.
Abnormality of the immune system
MedGen UID:
867388
Concept ID:
C4021753
Anatomical Abnormality
An abnormality of the immune system.
Weak cry
MedGen UID:
65892
Concept ID:
C0234860
Finding

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. 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. 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. doi: 10.1177/088307389601100416. 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. 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. 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

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center