CMS22
MCID: MYS067
MIFTS: 36

Myasthenic Syndrome, Congenital, 22 (CMS22)

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

Aliases & Classifications for Myasthenic Syndrome, Congenital, 22

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 22:

Name: Myasthenic Syndrome, Congenital, 22 57 72 29 6
Congenital Myasthenic Syndrome 22 12 15
Prepl Deficiency 57 72
Cms22 57 72

Characteristics:

OMIM®:

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

Miscellaneous:
onset at birth
favorable response to ache inhibitor treatment
muscle weakness may improve with age
one patient has been reported (last curated february 2017)


HPO:

31
myasthenic syndrome, congenital, 22:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0080587
OMIM® 57 616224
OMIM Phenotypic Series 57 PS601462
MeSH 44 D020294

Summaries for Myasthenic Syndrome, Congenital, 22

UniProtKB/Swiss-Prot : 72 Myasthenic syndrome, congenital, 22: 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 include easy fatigability and muscle weakness. CMS22 is an autosomal recessive form characterized by neonatal hypotonia.

MalaCards based summary : Myasthenic Syndrome, Congenital, 22, also known as congenital myasthenic syndrome 22, is related to hypotonia and congenital myasthenic syndrome. An important gene associated with Myasthenic Syndrome, Congenital, 22 is PREPL (Prolyl Endopeptidase Like). The drugs Sulfamethoxazole and Anti-Infective Agents have been mentioned in the context of this disorder. Related phenotypes are ptosis and muscle weakness

Disease Ontology : 12 A congenital myasthenic syndrome characterized by neonatal hypotonia, neonatal feeding problems, and nasal dysarthria and that has material basis in homozygous or compound heterozygous mutation in the PREPL gene on chromosome 2p21.

More information from OMIM: 616224 PS601462

Related Diseases for Myasthenic Syndrome, Congenital, 22

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, 22 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 hypotonia 30.4 PREPL CAMKMT
2 congenital myasthenic syndrome 29.7 PREPL CACNA1A BCHE
3 hypotonia-cystinuria syndrome 29.4 SLC3A1 PREPL PREP CAMKMT
4 cystinuria 29.4 SLC3A1 PREPL PREP CAMKMT
5 ptosis 10.2
6 growth hormone deficiency 10.2
7 maternal uniparental disomy 10.2
8 uniparental disomy of chromosome 2 10.0
9 maternal uniparental disomy of chromosome 2 10.0
10 2p21 microdeletion syndrome without cystinuria 10.0 PREPL CAMKMT
11 epileptic encephalopathy, childhood-onset 10.0 FGF12 CACNA1A
12 prader-willi syndrome 10.0
13 autosomal recessive disease 10.0
14 microcephaly 10.0
15 hypogonadism 10.0
16 ureteral disease 10.0 SLC3A1 PREPL
17 myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency 10.0 PREPL BCHE
18 neuromuscular junction disease 9.9 PREPL BCHE
19 urolithiasis 9.8 SLC3A1 PREPL
20 amnestic disorder 9.8 PREP BCHE

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 22:



Diseases related to Myasthenic Syndrome, Congenital, 22

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 22

Human phenotypes related to Myasthenic Syndrome, Congenital, 22:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 ptosis 31 HP:0000508
2 muscle weakness 31 HP:0001324
3 short stature 31 HP:0004322
4 waddling gait 31 HP:0002515
5 motor delay 31 HP:0001270
6 tented upper lip vermilion 31 HP:0010804
7 feeding difficulties 31 HP:0011968
8 generalized hypotonia 31 HP:0001290
9 decreased response to growth hormone stimuation test 31 HP:0000824

Symptoms via clinical synopsis from OMIM®:

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

Abdomen Gastrointestinal:
feeding difficulties

Muscle Soft Tissue:
hypotonia
muscle weakness, predominantly proximal
myasthenic syndrome
decreased mepp and mepc amplitudes
decreased quantal content
more
Head And Neck Mouth:
tented upper lip

Growth Height:
short stature

Endocrine Features:
growth hormone deficiency

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

Laboratory Abnormalities:
no cystinuria

Clinical features from OMIM®:

616224 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Myasthenic Syndrome, Congenital, 22:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 8.92 CAMKMT PREP PREPL SLC3A1

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 22

Drugs for Myasthenic Syndrome, Congenital, 22 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Sulfamethoxazole Approved Phase 2 723-46-6 5329
2 Anti-Infective Agents Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Sulfamethoxazole for the Treatment of Primary PREPL Deficiency (In Dutch: Sulfamethoxazole Ter Behandeling Van Primaire PREPL deficiëntie) Unknown status NCT02640443 Phase 2 Sulfamethoxazole

Search NIH Clinical Center for Myasthenic Syndrome, Congenital, 22

Genetic Tests for Myasthenic Syndrome, Congenital, 22

Genetic tests related to Myasthenic Syndrome, Congenital, 22:

# Genetic test Affiliating Genes
1 Myasthenic Syndrome, Congenital, 22 29 PREPL

Anatomical Context for Myasthenic Syndrome, Congenital, 22

Publications for Myasthenic Syndrome, Congenital, 22

Articles related to Myasthenic Syndrome, Congenital, 22:

(show all 12)
# Title Authors PMID Year
1
PREPL deficiency: delineation of the phenotype and development of a functional blood assay. 57 6
28726805 2018
2
PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. 57 6
24610330 2014
3
CNVs cause autosomal recessive genetic diseases with or without involvement of SNV/indels. 6
32576985 2020
4
Isolated PREPL deficiency associated with congenital myasthenic syndrome-22. 6
29913539 2018
5
The second point mutation in PREPL: a case report and literature review. 6
29483676 2018
6
Deletion of PREPl causes growth impairment and hypotonia in mice. 57
24586561 2014
7
Further delineation of genotype-phenotype correlation in homozygous 2p21 deletion syndromes: first description of patients without cystinuria. 57
23794250 2013
8
Two novel deletions in hypotonia-cystinuria syndrome. 6
22796000 2012
9
A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings. 61
32707643 2020
10
First maternal uniparental disomy for chromosome 2 with PREPL novel frameshift mutation of congenital myasthenic syndrome 22 in an infant. 61
31985178 2020
11
Assessment of the diversity of Paenibacillus species in environmental samples by a novel rpoB-based PCR-DGGE method. 61
16329951 2005
12
Application of a novel Paenibacillus-specific PCR-DGGE method and sequence analysis to assess the diversity of Paenibacillus spp. in the maize rhizosphere. 61
12782377 2003

Variations for Myasthenic Syndrome, Congenital, 22

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 22:

6 (show top 50) (show all 187)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PREPL NM_001171603.1(PREPL):c.807del (p.Ile269_Met270insTer) Deletion Pathogenic 390242 rs1057523690 GRCh37: 2:44566448-44566448
GRCh38: 2:44339309-44339309
2 PREPL and overlap with 1 gene(s) NC_000002.12:g.(?_44321336)_(44359735_?)del Deletion Pathogenic 478305 GRCh37:
GRCh38: 2:44321336-44359735
3 PREPL NC_000002.11:g.44559541_44571008del Deletion Pathogenic 548710 GRCh37:
GRCh38:
4 PREPL NM_001171603.1(PREPL):c.361_364del (p.Val121fs) Deletion Pathogenic 548711 rs1436090495 GRCh37: 2:44571704-44571707
GRCh38: 2:44344565-44344568
5 PREPL NM_001171603.1(PREPL):c.1604T>G (p.Leu535Ter) SNV Pathogenic 548712 rs1553352792 GRCh37: 2:44553993-44553993
GRCh38: 2:44326854-44326854
6 PREPL NM_001171603.1(PREPL):c.883C>T (p.Arg295Ter) SNV Pathogenic 548713 rs145356495 GRCh37: 2:44566372-44566372
GRCh38: 2:44339233-44339233
7 PREPL NM_001171603.1(PREPL):c.694C>T (p.Arg232Ter) SNV Pathogenic 573441 rs1361739547 GRCh37: 2:44569614-44569614
GRCh38: 2:44342475-44342475
8 PREPL NM_001171603.1(PREPL):c.434del (p.Leu145fs) Deletion Pathogenic 583046 rs775517492 GRCh37: 2:44571066-44571066
GRCh38: 2:44343927-44343927
9 PREPL and overlap with 1 gene(s) NC_000002.12:g.(?_44321336)_(44346410_?)del Deletion Pathogenic 583811 GRCh37: 2:44548475-44573549
GRCh38: 2:44321336-44346410
10 overlap with 2 genes NC_000002.12:g.(?_44280716)_(44346390_?)del Deletion Pathogenic 584389 GRCh37: 2:44507855-44573529
GRCh38: 2:44280716-44346390
11 PREPL NM_001171603.1(PREPL):c.715_718del (p.Lys239fs) Deletion Pathogenic 653242 rs779488471 GRCh37: 2:44569590-44569593
GRCh38: 2:44342451-44342454
12 PREPL NM_001171603.1(PREPL):c.1282_1285del (p.Phe428fs) Deletion Pathogenic 691883 rs748639083 GRCh37: 2:44559666-44559669
GRCh38: 2:44332527-44332530
13 PREPL NC_000002.12:g.(?_44321346)_(44359725_?)del Deletion Pathogenic 830511 GRCh37: 2:44548485-44586864
GRCh38:
14 PREPL and overlap with 1 gene(s) NC_000002.12:g.(?_44320179)_(44346410_?)del Deletion Pathogenic 832574 GRCh37: 2:44547318-44573549
GRCh38:
15 PREPL NC_000002.12:g.(?_44359487)_(44359725_?)del Deletion Pathogenic 832630 GRCh37: 2:44586626-44586864
GRCh38:
16 PREPL NM_001171613.2(PREPL):c.75del (p.Val26fs) Deletion Pathogenic 850079 GRCh37: 2:44573407-44573407
GRCh38: 2:44346268-44346268
17 overlap with 2 genes GRCh37/hg19 2p21(chr2:44494834-44571747) copy number loss Pathogenic 915960 GRCh37: 2:44494834-44571747
GRCh38:
18 PREPL NM_001171613.2(PREPL):c.-42del Deletion Pathogenic 953650 GRCh37: 2:44573523-44573523
GRCh38: 2:44346384-44346384
19 PREPL NM_001171613.2(PREPL):c.1554G>A (p.Trp518Ter) SNV Pathogenic 997672 GRCh37: 2:44550476-44550476
GRCh38: 2:44323337-44323337
20 PREPL NM_001171603.1(PREPL):c.307C>T (p.Gln103Ter) SNV Pathogenic 478315 rs200761047 GRCh37: 2:44573442-44573442
GRCh38: 2:44346303-44346303
21 PREPL NM_001171613.2(PREPL):c.1521_1522dup (p.Leu508fs) Microsatellite Pathogenic 943784 GRCh37: 2:44550507-44550508
GRCh38: 2:44323368-44323369
22 PREPL NM_001171613.2(PREPL):c.158_162del (p.Tyr53fs) Deletion Pathogenic 1032398 GRCh37: 2:44571071-44571075
GRCh38: 2:44343932-44343936
23 PREPL NM_001171603.1(PREPL):c.1155+1G>A SNV Pathogenic/Likely pathogenic 569764 rs758019788 GRCh37: 2:44565489-44565489
GRCh38: 2:44338350-44338350
24 PREPL NM_001171603.1(PREPL):c.1529+1G>A SNV Likely pathogenic 566684 rs1172015222 GRCh37: 2:44556075-44556075
GRCh38: 2:44328936-44328936
25 PREPL NM_001171603.1(PREPL):c.220-2A>G SNV Likely pathogenic 544536 rs753545038 GRCh37: 2:44573531-44573531
GRCh38: 2:44346392-44346392
26 PREPL NM_001171613.2(PREPL):c.1366C>T (p.Gln456Ter) SNV Likely pathogenic 974874 GRCh37: 2:44553964-44553964
GRCh38: 2:44326825-44326825
27 PREPL NM_001171613.2(PREPL):c.1553G>A (p.Trp518Ter) SNV Likely pathogenic 1030066 GRCh37: 2:44550477-44550477
GRCh38: 2:44323338-44323338
28 PREPL NM_001171603.1(PREPL):c.2020+1G>T SNV Likely pathogenic 649028 rs148092524 GRCh37: 2:44549869-44549869
GRCh38: 2:44322730-44322730
29 PREPL NM_001171603.1(PREPL):c.1248dup (p.Tyr417fs) Duplication Likely pathogenic 524111 rs1553354962 GRCh37: 2:44559702-44559703
GRCh38: 2:44332563-44332564
30 PREPL NM_001171613.2(PREPL):c.538A>G (p.Ile180Val) SNV Uncertain significance 848611 GRCh37: 2:44566450-44566450
GRCh38: 2:44339311-44339311
31 PREPL NM_001171613.2(PREPL):c.1760A>G (p.Gln587Arg) SNV Uncertain significance 848829 GRCh37: 2:44549033-44549033
GRCh38: 2:44321894-44321894
32 PREPL NM_001171613.2(PREPL):c.1300G>A (p.Gly434Ser) SNV Uncertain significance 859290 GRCh37: 2:44554030-44554030
GRCh38: 2:44326891-44326891
33 PREPL NM_001171613.2(PREPL):c.405C>A (p.Asn135Lys) SNV Uncertain significance 933423 GRCh37: 2:44569636-44569636
GRCh38: 2:44342497-44342497
34 PREPL NM_001171613.2(PREPL):c.1396C>G (p.Leu466Val) SNV Uncertain significance 947119 GRCh37: 2:44553934-44553934
GRCh38: 2:44326795-44326795
35 PREPL NM_001171613.2(PREPL):c.517A>G (p.Ser173Gly) SNV Uncertain significance 952039 GRCh37: 2:44566471-44566471
GRCh38: 2:44339332-44339332
36 PREPL NM_001171613.2(PREPL):c.1546G>A (p.Glu516Lys) SNV Uncertain significance 953636 GRCh37: 2:44550484-44550484
GRCh38: 2:44323345-44323345
37 PREPL NM_001171613.2(PREPL):c.425A>T (p.Tyr142Phe) SNV Uncertain significance 957189 GRCh37: 2:44569616-44569616
GRCh38: 2:44342477-44342477
38 PREPL NM_001171613.2(PREPL):c.-49+1678C>G SNV Uncertain significance 957622 GRCh37: 2:44586841-44586841
GRCh38: 2:44359702-44359702
39 PREPL NM_001171613.2(PREPL):c.1726G>A (p.Ala576Thr) SNV Uncertain significance 961539 GRCh37: 2:44549897-44549897
GRCh38: 2:44322758-44322758
40 PREPL NM_001171613.2(PREPL):c.1796G>A (p.Gly599Asp) SNV Uncertain significance 967466 GRCh37: 2:44548997-44548997
GRCh38: 2:44321858-44321858
41 PREPL NM_001171603.1(PREPL):c.1529G>A (p.Arg510Gln) SNV Uncertain significance 650135 rs754572953 GRCh37: 2:44556076-44556076
GRCh38: 2:44328937-44328937
42 PREPL NM_001171613.2(PREPL):c.1022A>G (p.Glu341Gly) SNV Uncertain significance 934206 GRCh37: 2:44559662-44559662
GRCh38: 2:44332523-44332523
43 PREPL NM_001171613.2(PREPL):c.505C>G (p.Leu169Val) SNV Uncertain significance 942750 GRCh37: 2:44566483-44566483
GRCh38: 2:44339344-44339344
44 PREPL NM_001171613.2(PREPL):c.206T>C (p.Ile69Thr) SNV Uncertain significance 955678 GRCh37: 2:44571027-44571027
GRCh38: 2:44343888-44343888
45 PREPL NM_001171613.2(PREPL):c.-49+1707A>G SNV Uncertain significance 962592 GRCh37: 2:44586812-44586812
GRCh38: 2:44359673-44359673
46 PREPL NM_001171613.2(PREPL):c.1368A>C (p.Gln456His) SNV Uncertain significance 963012 GRCh37: 2:44553962-44553962
GRCh38: 2:44326823-44326823
47 PREPL NM_001171613.2(PREPL):c.1673G>A (p.Arg558Gln) SNV Uncertain significance 963907 GRCh37: 2:44549950-44549950
GRCh38: 2:44322811-44322811
48 PREPL NM_001171613.2(PREPL):c.137AAG[1] (p.Glu47del) Microsatellite Uncertain significance 1030067 GRCh37: 2:44571659-44571661
GRCh38: 2:44344520-44344522
49 PREPL NM_001171613.2(PREPL):c.1808T>C (p.Ile603Thr) SNV Uncertain significance 946116 GRCh37: 2:44548985-44548985
GRCh38: 2:44321846-44321846
50 PREPL , SLC3A1 NM_001171613.2(PREPL):c.1839A>C (p.Gln613His) SNV Uncertain significance 947865 GRCh37: 2:44548573-44548573
GRCh38: 2:44321434-44321434

Expression for Myasthenic Syndrome, Congenital, 22

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 22.

Pathways for Myasthenic Syndrome, Congenital, 22

GO Terms for Myasthenic Syndrome, Congenital, 22

Molecular functions related to Myasthenic Syndrome, Congenital, 22 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 amyloid-beta binding GO:0001540 8.62 CACNA1A BCHE

Sources for Myasthenic Syndrome, Congenital, 22

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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