CMS3B
MCID: MYS049
MIFTS: 23

Myasthenic Syndrome, Congenital, 3b, Fast-Channel (CMS3B)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 3b, Fast-Channel:

Name: Myasthenic Syndrome, Congenital, 3b, Fast-Channel 57 72
Congenital Myasthenic Syndrome 3b 12 29 6
Cms3b 57 12 72
Myasthenic Syndrome, Congenital, Type 3b, Fast-Channel 39
Congenital Myasthenic Syndrome 3b, Fast-Channel 12

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
may respond to cholinesterase inhibitors of amifampridine


HPO:

31
myasthenic syndrome, congenital, 3b, fast-channel:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0110665
OMIM® 57 616322
OMIM Phenotypic Series 57 PS601462
MeSH 44 D020294

Summaries for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

UniProtKB/Swiss-Prot : 72 Myasthenic syndrome, congenital, 3B, fast-channel: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre- synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS3B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.

MalaCards based summary : Myasthenic Syndrome, Congenital, 3b, Fast-Channel, is also known as congenital myasthenic syndrome 3b. An important gene associated with Myasthenic Syndrome, Congenital, 3b, Fast-Channel is CHRND (Cholinergic Receptor Nicotinic Delta Subunit). Related phenotypes are decreased fetal movement and ptosis

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of postsynaptic neuromuscular junction defects resulting in rapid decay in endplate current and a failure to reach the threshold for depolarization and early onset progressive muscular weakness that has material basis in homozygous or compound heterozygous mutation in the CHRND gene on chromosome 2q37.

OMIM® : 57 Fast-channel congenital myasthenic syndrome (FCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor channel, specifically from abnormally brief opening and activity of the channel, with a rapid decay in endplate current and a failure to reach the threshold for depolarization. Treatment with pyridostigmine or amifampridine may be helpful; quinine, quinidine, and fluoxetine should be avoided (summary by Sine et al., 2003 and Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (616322) (Updated 05-Apr-2021)

Related Diseases for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

Diseases in the Myasthenic Syndrome, Congenital, 1b, Fast-Channel family:

Myasthenic Syndrome, Congenital, 3b, Fast-Channel Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

Human phenotypes related to Myasthenic Syndrome, Congenital, 3b, Fast-Channel:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 decreased fetal movement 31 occasional (7.5%) HP:0001558
2 ptosis 31 HP:0000508
3 facial palsy 31 HP:0010628
4 high palate 31 HP:0000218
5 respiratory insufficiency 31 HP:0002093
6 neonatal hypotonia 31 HP:0001319
7 easy fatigability 31 HP:0003388
8 ophthalmoplegia 31 HP:0000602
9 feeding difficulties 31 HP:0011968
10 neck muscle weakness 31 HP:0000467

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
ptosis
ophthalmoplegia

Respiratory:
respiratory insufficiency

Head And Neck Mouth:
high-arched palate

Abdomen Gastrointestinal:
poor feeding

Neurologic Central Nervous System:
delayed motor development due to muscle weakness

Muscle Soft Tissue:
muscle weakness
easy fatigability
hypotonia, neonatal
decremental response to repetitive nerve stimulation
decreased amplitudes of the miniature endplate potential (mepp) and current (mepc)
more
Head And Neck Neck:
neck muscle weakness

Head And Neck Face:
facial muscle weakness

Prenatal Manifestations Movement:
decreased fetal movements (in some patients)

Skeletal Hands:
hand contractures (in some patients)

Clinical features from OMIM®:

616322 (Updated 05-Apr-2021)

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

Genetic Tests for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

Genetic tests related to Myasthenic Syndrome, Congenital, 3b, Fast-Channel:

# Genetic test Affiliating Genes
1 Congenital Myasthenic Syndrome 3b 29 CHRND

Anatomical Context for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

Publications for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

Articles related to Myasthenic Syndrome, Congenital, 3b, Fast-Channel:

# Title Authors PMID Year
1
Congenital myasthenia-related AChR delta subunit mutation interferes with intersubunit communication essential for channel gating. 6 57
18398509 2008
2
Congenital myasthenic syndrome caused by low-expressor fast-channel AChR delta subunit mutation. 57 6
12499478 2002
3
Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita. 57 6
11435464 2001
4
Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. 57
25792100 2015
5
Mechanistic diversity underlying fast channel congenital myasthenic syndromes. 57
14592870 2003

Variations for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 3b, Fast-Channel:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CHRND NM_000751.3(CHRND):c.812C>A (p.Pro271Gln) SNV Pathogenic 18364 rs121909503 GRCh37: 2:233394841-233394841
GRCh38: 2:232530131-232530131
2 CHRND NM_000751.3(CHRND):c.236T>A (p.Ile79Lys) SNV Pathogenic 18365 rs121909509 GRCh37: 2:233392148-233392148
GRCh38: 2:232527438-232527438
3 CHRND NM_000751.3(CHRND):c.238G>A (p.Glu80Lys) SNV Pathogenic 18366 rs121909504 GRCh37: 2:233392150-233392150
GRCh38: 2:232527440-232527440
4 CHRND NM_000751.3(CHRND):c.820_820+1del Deletion Pathogenic 18367 rs879255564 GRCh37: 2:233394849-233394850
GRCh38: 2:232530139-232530140
5 CHRND NM_000751.3(CHRND):c.188T>C (p.Leu63Pro) SNV Pathogenic 18371 rs121909508 GRCh37: 2:233391374-233391374
GRCh38: 2:232526664-232526664
6 CHRND NM_000751.3(CHRND):c.1181A>C (p.Lys394Thr) SNV Uncertain significance 548627 rs1553575390 GRCh37: 2:233398774-233398774
GRCh38: 2:232534064-232534064
7 CHRND NM_000751.3(CHRND):c.1220G>A (p.Arg407Gln) SNV Uncertain significance 286380 rs563035306 GRCh37: 2:233398813-233398813
GRCh38: 2:232534103-232534103
8 CHRND NM_000751.3(CHRND):c.919C>T (p.Pro307Ser) SNV Uncertain significance 281423 rs142063328 GRCh37: 2:233396160-233396160
GRCh38: 2:232531450-232531450
9 CHRND NM_000751.3(CHRND):c.727C>T (p.Arg243Cys) SNV Uncertain significance 283138 rs201733876 GRCh37: 2:233394756-233394756
GRCh38: 2:232530046-232530046

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 3b, Fast-Channel:

72
# Symbol AA change Variation ID SNP ID
1 CHRND p.Glu80Lys VAR_021210 rs121909504
2 CHRND p.Pro271Gln VAR_021211 rs121909503
3 CHRND p.Leu42Pro VAR_073691
4 CHRND p.Ile79Lys VAR_073692 rs121909509

Expression for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 3b, Fast-Channel.

Pathways for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

GO Terms for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

Sources for Myasthenic Syndrome, Congenital, 3b, Fast-Channel

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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