CMS19
MCID: MYS070
MIFTS: 42

Myasthenic Syndrome, Congenital, 19 (CMS19)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 19

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 19:

Name: Myasthenic Syndrome, Congenital, 19 57 72 29 6
Cms19 57 12 72
Congenital Myasthenic Syndrome 19 12 15
Myasthenic Syndrome, Congenital, Type 19 39

Characteristics:

OMIM®:

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

Miscellaneous:
onset at birth
three patients from 2 unrelated families have been reported (last curated december 2015)
possible benefit from treatment with 3,4-diaminopyridine and salbutamol


HPO:

31
myasthenic syndrome, congenital, 19:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 19

UniProtKB/Swiss-Prot : 72 Myasthenic syndrome, congenital, 19: 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.

MalaCards based summary : Myasthenic Syndrome, Congenital, 19, also known as cms19, is related to sclerosteosis 2 and myasthenic syndrome, congenital, 13. An important gene associated with Myasthenic Syndrome, Congenital, 19 is COL13A1 (Collagen Type XIII Alpha 1 Chain), and among its related pathways/superpathways are Transmission across Chemical Synapses and Degradation of the extracellular matrix. Related phenotypes are facial palsy and spinal rigidity

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of defects in the neuromuscular junction resulting in generalized muscle weakness, exercise intolerance, and respiratory insufficiency that has material basis in homozygous mutation in the COL13A1 gene on chromosome 10q22.

OMIM® : 57 Congenital myasthenic syndrome-19 is an autosomal recessive disorder resulting from a defect in the neuromuscular junction, causing generalized muscle weakness, exercise intolerance, and respiratory insufficiency. Patients present with hypotonia, feeding difficulties, and respiratory problems soon after birth, but the severity of the weakness and disease course is variable (summary by Logan et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (616720) (Updated 05-Apr-2021)

Related Diseases for Myasthenic Syndrome, Congenital, 19

Diseases in the Congenital Myasthenic Syndrome family:

Myasthenic Syndrome, Congenital, 10 Myasthenic Syndrome, Congenital, 5
Myasthenic Syndrome, Congenital, 12 Myasthenic Syndrome, Congenital, 16
Myasthenic Syndrome, Congenital, 13 Myasthenic Syndrome, Congenital, 8
Myasthenic Syndrome, Congenital, 22 Myasthenic Syndrome, Congenital, 15
Myasthenic Syndrome, Congenital, 14 Myasthenic Syndrome, Congenital, 17
Myasthenic Syndrome, Congenital, 18 Myasthenic Syndrome, Congenital, 19

Diseases related to Myasthenic Syndrome, Congenital, 19 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 22)
# Related Disease Score Top Affiliating Genes
1 sclerosteosis 2 10.2 RAPSN DOK7
2 myasthenic syndrome, congenital, 13 10.1 RAPSN DOK7
3 cenani-lenz syndactyly syndrome 10.0 RAPSN MUSK DOK7
4 polyhydramnios 10.0 RAPSN MUSK DOK7
5 congenital myasthenic syndrome with episodic apnea 9.9 SLC5A7 CHAT
6 postsynaptic congenital myasthenic syndromes 9.9 RAPSN MUSK DOK7 COL13A1
7 developmental and epileptic encephalopathy 5 9.8 CDK5 CAST
8 fetal akinesia deformation sequence 1 9.8 SLC18A3 RAPSN MUSK DOK7
9 tendinosis 9.7 SLC18A3 CHAT
10 congenital myasthenic syndrome associated with acetylcholine receptor deficiency 9.7 RAPSN MUSK CHAT
11 myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency 9.7 RAPSN MUSK CHAT
12 myasthenic syndrome, congenital, 21, presynaptic 9.6 SLC18A3 RAPSN DOK7 CHAT
13 muscular dystrophy, congenital, lmna-related 9.6 RAPSN HSPG2 DOK7
14 scrapie 9.6 CHAT CDK5 CAST
15 peripheral nervous system disease 9.5 RAPSN MUSK DOK7 CHAT
16 dementia, lewy body 9.4 SNAP25 CHAT CDK5
17 neuromuscular disease 9.4 SYT2 RAPSN MUSK DOK7 CHAT
18 neuromuscular junction disease 9.3 SYT2 RAPSN MUSK DOK7 COL13A1 CHAT
19 presynaptic congenital myasthenic syndromes 9.2 SYT2 SNAP25 SLC5A7 SLC18A3 COL13A1 CHAT
20 amyotrophic lateral sclerosis 1 9.1 UNC13A SLC5A7 SLC18A3 CRK CHAT CDK5
21 ptosis 8.8 SNAP25 SLC5A7 SLC18A3 RAPSN MUSK DOK7
22 congenital myasthenic syndrome 8.1 UNC13A SYT2 SNTB2 SNAP25 SLC5A7 SLC18A3

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 19:



Diseases related to Myasthenic Syndrome, Congenital, 19

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 19

Human phenotypes related to Myasthenic Syndrome, Congenital, 19:

31 (show all 19)
# Description HPO Frequency HPO Source Accession
1 facial palsy 31 occasional (7.5%) HP:0010628
2 spinal rigidity 31 occasional (7.5%) HP:0003306
3 motor delay 31 occasional (7.5%) HP:0001270
4 pes cavus 31 occasional (7.5%) HP:0001761
5 distal joint laxity 31 occasional (7.5%) HP:0020152
6 ptosis 31 HP:0000508
7 high palate 31 HP:0000218
8 respiratory insufficiency 31 HP:0002093
9 pectus carinatum 31 HP:0000768
10 gastroesophageal reflux 31 HP:0002020
11 retrognathia 31 HP:0000278
12 micrognathia 31 HP:0000347
13 low-set ears 31 HP:0000369
14 poor head control 31 HP:0002421
15 feeding difficulties 31 HP:0011968
16 generalized hypotonia 31 HP:0001290
17 bulbar palsy 31 HP:0001283
18 recurrent lower respiratory tract infections 31 HP:0002783
19 exercise intolerance 31 HP:0003546

Symptoms via clinical synopsis from OMIM®:

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

Chest External Features:
pectus carinatum

Head And Neck Face:
retrognathia
micrognathia
facial weakness (in some patients)

Head And Neck Head:
poor head control

Head And Neck Mouth:
high-arched palate

Head And Neck Neck:
neck weakness

Skeletal:
distal joint laxity (in some patients)

Respiratory:
respiratory insufficiency
recurrent chest infections

Abdomen Gastrointestinal:
gastroesophageal reflux
feeding difficulties

Head And Neck Ears:
low-set ears

Muscle Soft Tissue:
exercise intolerance
hypotonia
muscle weakness, proximal and distal
bulbar weakness
decreased muscle bulk
more
Neurologic Central Nervous System:
delayed motor development (in some patients)
learning disabilities (in some patients)

Skeletal Feet:
pes cavus (in some patients)

Skeletal Spine:
spinal rigidity (in some patients)

Clinical features from OMIM®:

616720 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Myasthenic Syndrome, Congenital, 19 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 9.5 MUSK
2 Decreased viability GR00055-A-2 9.5 MUSK
3 Decreased viability GR00154-A 9.5 CDK5
4 Decreased viability GR00173-A 9.5 MUSK
5 Decreased viability GR00221-A-1 9.5 CRKL MUSK
6 Decreased viability GR00221-A-2 9.5 CRKL
7 Decreased viability GR00221-A-4 9.5 CDK5 CRKL MUSK SYT2
8 Decreased viability GR00249-S 9.5 CDK5 CRKL
9 Decreased viability GR00381-A-1 9.5 SYT2
10 Decreased viability GR00386-A-1 9.5 SYT2

MGI Mouse Phenotypes related to Myasthenic Syndrome, Congenital, 19:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.18 CAST CDK5 CHAT COL13A1 DOK7 HSPG2
2 homeostasis/metabolism MP:0005376 10.1 CAST CDK5 CHAT COL13A1 CRK HSPG2
3 mortality/aging MP:0010768 10.1 CAST CDK5 CHAT CRK CRKL DOK7
4 nervous system MP:0003631 9.86 CAST CDK5 CHAT COL13A1 CRK CRKL
5 muscle MP:0005369 9.81 CHAT COL13A1 CRK DOK7 HSPG2 MUSK
6 respiratory system MP:0005388 9.32 CDK5 CHAT CRK DOK7 HSPG2 MUSK

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 19

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 19

Genetic Tests for Myasthenic Syndrome, Congenital, 19

Genetic tests related to Myasthenic Syndrome, Congenital, 19:

# Genetic test Affiliating Genes
1 Myasthenic Syndrome, Congenital, 19 29 COL13A1

Anatomical Context for Myasthenic Syndrome, Congenital, 19

Publications for Myasthenic Syndrome, Congenital, 19

Articles related to Myasthenic Syndrome, Congenital, 19:

# Title Authors PMID Year
1
Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain. 57 6
26626625 2015
2
The clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutations. 6
31081514 2019
3
Muscle-derived collagen XIII regulates maturation of the skeletal neuromuscular junction. 57
20844119 2010
4
Lack of cytosolic and transmembrane domains of type XIII collagen results in progressive myopathy. 57
11583983 2001
5
Collagen XIII Is Required for Neuromuscular Synapse Regeneration and Functional Recovery after Peripheral Nerve Injury. 61
29626165 2018

Variations for Myasthenic Syndrome, Congenital, 19

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 19:

6 (show all 13)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 COL13A1 NM_001130103.1(COL13A1):c.523-1delG Deletion Pathogenic 218906 rs864309663 GRCh37: 10:71648059-71648059
GRCh38: 10:69888303-69888303
2 COL13A1 NM_001368882.1(COL13A1):c.1138C>T (p.Gln380Ter) SNV Pathogenic 975954 GRCh37: 10:71681686-71681686
GRCh38: 10:69921930-69921930
3 COL13A1 NM_001368882.1(COL13A1):c.1559G>A (p.Gly520Asp) SNV Pathogenic 982128 GRCh37: 10:71690184-71690184
GRCh38: 10:69930428-69930428
4 COL13A1 NM_001368882.1(COL13A1):c.630+2T>C SNV Pathogenic 717621 rs546473709 GRCh37: 10:71654336-71654336
GRCh38: 10:69894580-69894580
5 COL13A1 NM_001368882.1(COL13A1):c.967-2A>G SNV Pathogenic 998286 GRCh37: 10:71678039-71678039
GRCh38: 10:69918283-69918283
6 COL13A1 NM_001130103.2(COL13A1):c.1173del (p.Leu392fs) Deletion Pathogenic 218905 rs864309662 GRCh37: 10:71682524-71682524
GRCh38: 10:69922768-69922768
7 COL13A1 NM_001368882.1(COL13A1):c.513del (p.Gly172fs) Deletion Likely pathogenic 977150 GRCh37: 10:71640309-71640309
GRCh38: 10:69880553-69880553
8 COL13A1 NM_001368882.1(COL13A1):c.685-1164T>C SNV Likely pathogenic 488484 rs1554943789 GRCh37: 10:71657289-71657289
GRCh38: 10:69897533-69897533
9 COL13A1 NM_001368882.1(COL13A1):c.576+5G>A SNV Uncertain significance 977151 GRCh37: 10:71648091-71648091
GRCh38: 10:69888335-69888335
10 COL13A1 NM_001368882.1(COL13A1):c.567C>A (p.Asp189Glu) SNV Uncertain significance 1031125 GRCh37: 10:71648077-71648077
GRCh38: 10:69888321-69888321
11 COL13A1 NM_001368882.1(COL13A1):c.1610A>G (p.Lys537Arg) SNV Uncertain significance 1033311 GRCh37: 10:71690235-71690235
GRCh38: 10:69930479-69930479
12 COL13A1 NM_001368882.1(COL13A1):c.750+18G>T SNV Uncertain significance 1033312 GRCh37: 10:71658536-71658536
GRCh38: 10:69898780-69898780
13 COL13A1 NM_001130103.2(COL13A1):c.2007C>T (p.Pro669=) SNV Uncertain significance 548475 rs555259357 GRCh37: 10:71707080-71707080
GRCh38: 10:69947324-69947324

Expression for Myasthenic Syndrome, Congenital, 19

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 19.

Pathways for Myasthenic Syndrome, Congenital, 19

Pathways related to Myasthenic Syndrome, Congenital, 19 according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.68 SYT2 SNAP25 SLC5A7 SLC18A3 CHAT
2
Show member pathways
12.21 NID2 MUSK HSPG2 COL13A1 CAST
3
Show member pathways
12.02 NID2 HSPG2 CRKL CRK
4
Show member pathways
11.75 UNC13A SNAP25 SLC18A3
5
Show member pathways
11.6 CRKL CRK CDK5
6
Show member pathways
11.49 SNAP25 SLC5A7 SLC18A3 CHAT
7 10.97 CRKL CDK5
8 10.94 CRKL CRK
9 10.82 CRKL CRK
10 10.66 CRKL CRK
11 10.44 CRKL CRK
12 9.88 SLC5A7 SLC18A3 CHAT

GO Terms for Myasthenic Syndrome, Congenital, 19

Cellular components related to Myasthenic Syndrome, Congenital, 19 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 10.1 UNC13A SYT2 SNTB2 SNAP25 SLC5A7 SLC18A3
2 cell junction GO:0030054 9.85 UNC13A SYT2 SNTB2 SNAP25 SLC5A7 RAPSN
3 neuron projection GO:0043005 9.71 UNC13A SNAP25 CHAT CDK5
4 axon GO:0030424 9.67 SYT2 SNAP25 SLC5A7 CDK5
5 presynapse GO:0098793 9.62 UNC13A SLC5A7 CHAT CDK5
6 neuromuscular junction GO:0031594 9.43 UNC13A SLC5A7 RAPSN MUSK CRKL CDK5
7 synapse GO:0045202 9.4 UNC13A SYT2 SNTB2 SNAP25 SLC5A7 RAPSN

Biological processes related to Myasthenic Syndrome, Congenital, 19 according to GeneCards Suite gene sharing:

(show all 26)
# Name GO ID Score Top Affiliating Genes
1 exocytosis GO:0006887 9.75 UNC13A SNAP25 CDK5
2 neuron migration GO:0001764 9.74 CRKL CRK CDK5
3 cell-matrix adhesion GO:0007160 9.71 NID2 COL13A1 CDK5
4 cerebral cortex development GO:0021987 9.67 CRKL CRK CDK5
5 regulation of synaptic transmission, glutamatergic GO:0051966 9.63 UNC13A CDK5
6 hippocampus development GO:0021766 9.63 CRKL CRK CDK5
7 associative learning GO:0008306 9.62 SNAP25 CDK5
8 synaptic transmission, glutamatergic GO:0035249 9.62 UNC13A CDK5
9 synaptic vesicle exocytosis GO:0016079 9.61 SNAP25 CDK5
10 positive regulation of dendrite extension GO:1903861 9.61 UNC13A SYT2
11 neuromuscular synaptic transmission GO:0007274 9.6 SLC5A7 CHAT
12 synaptic transmission, cholinergic GO:0007271 9.59 SLC5A7 RAPSN
13 regulation of dendrite development GO:0050773 9.58 CRKL CRK
14 neurotransmitter biosynthetic process GO:0042136 9.56 SLC5A7 CHAT
15 synaptic vesicle priming GO:0016082 9.55 UNC13A SNAP25
16 regulation of cell adhesion mediated by integrin GO:0033628 9.52 CRKL CRK
17 synaptic vesicle docking GO:0016081 9.51 UNC13A SNAP25
18 reelin-mediated signaling pathway GO:0038026 9.48 CRKL CRK
19 regulation of T cell migration GO:2000404 9.43 CRKL CRK
20 neuromuscular junction development GO:0007528 9.43 UNC13A MUSK DOK7
21 regulation of leukocyte migration GO:0002685 9.4 CRKL CRK
22 cerebellar neuron development GO:0098749 9.37 CRKL CRK
23 chemical synaptic transmission GO:0007268 9.35 UNC13A SNAP25 SLC18A3 RAPSN CDK5
24 acetylcholine biosynthetic process GO:0008292 9.32 SLC5A7 CHAT
25 helper T cell diapedesis GO:0035685 9.16 CRKL CRK
26 neurotransmitter secretion GO:0007269 9.1 UNC13A SYT2 SNAP25 SLC5A7 SLC18A3 CHAT

Molecular functions related to Myasthenic Syndrome, Congenital, 19 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ephrin receptor binding GO:0046875 8.96 CRK CDK5
2 syntaxin-1 binding GO:0017075 8.62 UNC13A SNAP25

Sources for Myasthenic Syndrome, Congenital, 19

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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