Details of Disease

Disease Name

Congenital myasthenic syndrome

congenital myasthenia; myasthenia gravis congenital; familial limb-girdle myasthenia; erb-Goldflam syndrome; myasthenia gravis pseudoparalytica; congenital MG; Congenital Myasthenic Syndromes; CMS; myasthenic syndrome, congenital

Definition

Congenital myasthenic syndrome (CMS) is a group of genetic disorders of impaired neuromuscular transmission at the motor endplate characterized by fatigable muscle weakness.

Disease Hierarchy

DIS6SVEE: Syndromic disease

DISLG2RO: Hereditary neuromuscular disease

DIS8VKGV: Neuromuscular junction disease

DISJLG2T: Congenital myasthenic syndrome

Disease Identifiers

MONDO ID

MONDO_0018940

MESH ID

D020294

UMLS CUI

C0751882

MedGen ID

155650

Orphanet ID

590

SNOMED CT ID

230672006

General Information of Disease (ID: DISJLG2T)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 10 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CHRNA1	TT54JVQ	Limited	Genetic Variation	[1]
RPH3A	TT9L4J8	Limited	Autosomal recessive	[2]
UTRN	TTNO1VA	moderate	Biomarker	[3]
CHAT	TTKYFSB	Strong	Genetic Variation	[4]
MUSK	TT6SA0X	Strong	Genetic Variation	[5]
SCN4A	TT84DRB	Strong	CausalMutation	[6]
SLC18A3	TTV8KWS	Strong	Biomarker	[7]
SLC25A1	TTTD730	Strong	Genetic Variation	[8]
SLC5A7	TTRV7W3	Strong	Genetic Variation	[9]
RPH3A	TT9L4J8	Definitive	Genetic Variation	[10]
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⏷ Show the Full List of 10 DTT(s)

This Disease Is Related to 30 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CHD8	OTS7A6AF	Limited	Autosomal dominant	[2]
CHRND	OTLUUP7C	Limited	Genetic Variation	[11]
COLQ	OT4BHUGQ	Limited	Biomarker	[12]
GFPT1	OTQBDO45	Limited	Biomarker	[13]
LAMB2	OT71OI2Y	Limited	Biomarker	[14]
RPH3A	OT5VS65E	Limited	Autosomal recessive	[2]
COL13A1	OTM9IM6J	moderate	Genetic Variation	[15]
DAP	OT5YLL7E	moderate	Biomarker	[16]
EIF3K	OTGTKVGO	moderate	Genetic Variation	[17]
HNRNPH1	OTFRWOLM	moderate	Biomarker	[18]
HNRNPH2	OTMGP4J7	moderate	Biomarker	[18]
MYO9A	OTE3XHKY	moderate	Biomarker	[19]
SRSF1	OTF61HOV	moderate	Genetic Variation	[20]
AGRN	OTWJENAZ	Strong	Genetic Variation	[21]
ALG14	OTBM7K28	Strong	Biomarker	[22]
ALG2	OT77B384	Strong	Genetic Variation	[23]
C17orf107	OTOU43J4	Strong	CausalMutation	[24]
CD2AP	OTC76KQM	Strong	Genetic Variation	[25]
CHRNG	OTXC2UR7	Strong	Biomarker	[26]
DOK7	OTR2V7HO	Strong	Biomarker	[21]
DPAGT1	OTYEJAGZ	Strong	Genetic Variation	[27]
GMPPB	OTJ0CCJ8	Strong	Autosomal recessive	[28]
LAMA5	OTIIXE4M	Strong	Genetic Variation	[29]
LRP4	OTO4M459	Strong	Biomarker	[30]
MACF1	OTVIHD77	Strong	Biomarker	[31]
PLEC	OTU4XDEG	Strong	Autosomal recessive	[28]
RAPSN	OTGMSWDQ	Strong	Biomarker	[21]
SEMA7A	OT0ZJK64	Strong	Biomarker	[32]
CHRNE	OTGGXGGB	Definitive	Autosomal recessive	[33]
DNAJA3	OT61924T	Definitive	Biomarker	[34]
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⏷ Show the Full List of 30 DOT(s)

References

1	Muscle acetylcholine receptor conversion into chloride conductance at positive potentials by a single mutation.Proc Natl Acad Sci U S A. 2019 Oct 15;116(42):21228-21235. doi: 10.1073/pnas.1908284116. Epub 2019 Sep 30.
2	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
3	Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations.Hum Genet. 2000 Aug;107(2):160-4. doi: 10.1007/s004390000359.
4	How chromosomal deletions can unmask recessive mutations? Deletions in 10q11.2 associated with CHAT or SLC18A3 mutations lead to congenital myasthenic syndrome.Am J Med Genet A. 2018 Jan;176(1):151-155. doi: 10.1002/ajmg.a.38515. Epub 2017 Nov 12.
5	Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum.Am J Med Genet A. 2019 Apr;179(4):655-658. doi: 10.1002/ajmg.a.61060. Epub 2019 Feb 4.
6	A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis.Neurology. 2016 Jan 12;86(2):161-9. doi: 10.1212/WNL.0000000000002264. Epub 2015 Dec 11.
7	SLC18A3 variants lead to fetal akinesia deformation sequence early in pregnancy. Am J Med Genet A. 2019 Jul;179(7):1362-1365. doi: 10.1002/ajmg.a.61186. Epub 2019 May 6.
8	Congenital myasthenic syndrome with mild intellectual disability caused by a recurrent SLC25A1 variant.Eur J Hum Genet. 2020 Mar;28(3):373-377. doi: 10.1038/s41431-019-0506-2. Epub 2019 Sep 16.
9	The novel p.Ser263Phe mutation in the human high-affinity choline transporter 1 (CHT1/SLC5A7) causes a lethal form of fetal akinesia syndrome.Hum Mutat. 2019 Oct;40(10):1676-1683. doi: 10.1002/humu.23828. Epub 2019 Jul 12.
10	Presynaptic congenital myasthenic syndrome with altered synaptic vesicle homeostasis linked to compound heterozygous sequence variants in RPH3A.Mol Genet Genomic Med. 2018 May;6(3):434-440. doi: 10.1002/mgg3.370. Epub 2018 Feb 14.
11	New compound heterozygous variants of the cholinergic receptor nicotinic delta subunit gene in a Chinese male with congenital myasthenic syndrome: A case report.Medicine (Baltimore). 2017 Dec;96(51):e8981. doi: 10.1097/MD.0000000000008981.
12	Congenital myasthenic syndrome with novel pathogenic variants in the COLQ gene associated with the presence of antibodies to acetylcholine receptors.J Clin Neurosci. 2020 Feb;72:468-471. doi: 10.1016/j.jocn.2019.12.007. Epub 2019 Dec 10.
13	Phenotype of a limb-girdle congenital myasthenic syndrome patient carrying a GFPT1 mutation.Brain Dev. 2019 May;41(5):470-473. doi: 10.1016/j.braindev.2018.12.002. Epub 2019 Mar 4.
14	Congenital myasthenic syndromes: recent advances.Curr Opin Neurol. 2016 Oct;29(5):565-71. doi: 10.1097/WCO.0000000000000370.
15	Congenital myasthenic syndrome caused by novel COL13A1 mutations.J Neurol. 2019 May;266(5):1107-1112. doi: 10.1007/s00415-019-09239-7. Epub 2019 Feb 14.
16	Inherited disorders of the neuromuscular junction: an update.J Neurol. 2014 Nov;261(11):2234-43. doi: 10.1007/s00415-014-7520-7. Epub 2014 Oct 11.
17	Limb-girdle congenital myasthenic syndrome in a Chinese family with novel mutations in MUSK gene and literature review.Clin Neurol Neurosurg. 2016 Nov;150:41-45. doi: 10.1016/j.clineuro.2016.08.021. Epub 2016 Aug 22.
18	SRSF1 and hnRNP H antagonistically regulate splicing of COLQ exon 16 in a congenital myasthenic syndrome.Sci Rep. 2015 Aug 18;5:13208. doi: 10.1038/srep13208.
19	MYO9A deficiency in motor neurons is associated with reduced neuromuscular agrin secretion.Hum Mol Genet. 2018 Apr 15;27(8):1434-1446. doi: 10.1093/hmg/ddy054.
20	Splicing regulation and dysregulation of cholinergic genes expressed at the neuromuscular junction.J Neurochem. 2017 Aug;142 Suppl 2:64-72. doi: 10.1111/jnc.13954. Epub 2017 Mar 21.
21	Null variants in AGRN cause lethal fetal akinesia deformation sequence.Clin Genet. 2020 Apr;97(4):634-638. doi: 10.1111/cge.13677. Epub 2019 Dec 11.
22	Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. Brain. 2013 Mar;136(Pt 3):944-56. doi: 10.1093/brain/awt010. Epub 2013 Feb 11.
23	Trouble at the junction: When myopathy and myasthenia overlap.Muscle Nerve. 2019 Dec;60(6):648-657. doi: 10.1002/mus.26676. Epub 2019 Sep 10.
24	A common CHRNE mutation in Brazilian patients with congenital myasthenic syndrome.J Neurol. 2018 Mar;265(3):708-713. doi: 10.1007/s00415-018-8736-8. Epub 2018 Jan 30.
25	The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies.Curr Opin Neurol. 2019 Oct;32(5):696-703. doi: 10.1097/WCO.0000000000000736.
26	Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit. Am J Hum Genet. 2006 Aug;79(2):303-12. doi: 10.1086/506257. Epub 2006 Jun 20.
27	Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design.Cell. 2018 Nov 1;175(4):1045-1058.e16. doi: 10.1016/j.cell.2018.10.037.
28	The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
29	A presynaptic congenital myasthenic syndrome attributed to a homozygous sequence variant in LAMA5.Ann N Y Acad Sci. 2018 Feb;1413(1):119-125. doi: 10.1111/nyas.13585. Epub 2018 Jan 28.
30	Impaired Synaptic Development, Maintenance, and Neuromuscular Transmission in LRP4-Related Myasthenia.JAMA Neurol. 2015 Aug;72(8):889-96. doi: 10.1001/jamaneurol.2015.0853.
31	MACF1 links Rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses.J Cell Biol. 2019 May 6;218(5):1686-1705. doi: 10.1083/jcb.201810023. Epub 2019 Mar 6.
32	Premyogenic progenitors derived from human pluripotent stem cells expand in floating culture and differentiate into transplantable myogenic progenitors.Sci Rep. 2018 Apr 26;8(1):6555. doi: 10.1038/s41598-018-24959-y.
33	Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the epsilon subunit. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):758-62. doi: 10.1073/pnas.92.3.758.
34	Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction. Hum Mol Genet. 2010 Jun 15;19(12):2370-9. doi: 10.1093/hmg/ddq110. Epub 2010 Apr 6.