Myasthenic Syndrome, Congenital, 1a, Slow-channel; Cms1a

Description

Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction (NMJ). 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, as well as by pathologic mechanism and electrophysiologic studies (i.e., acetylcholine receptor (AChR) deficiency, slow-channel or fast-channel kinetic defects at the AChR) (summary by Engel et al., 2003; Engel et al., 2015). Approximately 10% of CMS cases are presynaptic, 15% are synaptic, and 75% are postsynaptic, the majority of which are caused by AChR deficiency (Engel et al., 2003).Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic NMJ characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the AChR channel, specifically prolonged opening and activity of the channel, which causes prolonged synaptic currents resulting in a depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. Treatment with quinine, quinidine, or fluoxetine may be helpful; acetylcholinesterase inhibitors and amifampridine should be avoided (summary by Engel et al., 2015). Genetic Heterogeneity of Congenital Myasthenic SyndromesRecessive mutations in subunits of the acetylcholine receptor are the most common cause of CMS (Harper, 2004). CMS1A and CMS1B (OMIM ) are caused by mutation in the CHRNA1 gene (OMIM ); CMS2A (OMIM ) and CMS2C (OMIM ) are caused by mutation in the CHRNB1 gene (OMIM ) on 17p12; CMS3A (OMIM ), CMS3B (OMIM ), and CMS3C (OMIM ) are caused by mutation in the CHRND gene (OMIM ) on 2q33; and CMS4A (OMIM ), CMS4B (OMIM ), and CMS4C (OMIM ) are caused by mutation in the CHRNE gene (OMIM ) on 17p13.CMS5 (OMIM ) is caused by mutation in the COLQ gene (OMIM ) on 3p25; CMS6 (OMIM ) is caused by mutation in the CHAT gene (OMIM ) on 10q; CMS7 (OMIM ) is caused by mutation in the SYT2 gene (OMIM ) on 1q32; CMS8 (OMIM ) is caused by mutation in the AGRN gene (OMIM ) on 1p; CMS9 (OMIM ) is caused by mutation in the MUSK gene (OMIM ) on 9q31; CMS10 (OMIM ) is caused by mutation in the DOK7 gene (OMIM ) on 4p; CMS11 (OMIM ) is caused by mutation in the RAPSN gene (OMIM ) on 11p11; CMS12 (OMIM ) is caused by mutation in the GFPT1 gene (OMIM ) on 2p14; CMS13 (OMIM ) is caused by mutation in the DPAGT1 gene (OMIM ) on 11q23; CMS14 (OMIM ) is caused by mutation in the ALG2 gene (OMIM ) on 9q22; CMS15 (OMIM ) is caused by mutation in the ALG14 gene (OMIM ) on 1p21; CMS16 (OMIM ) is caused by mutation in the SCN4A gene (OMIM ) on 17q; CMS17 (OMIM ) is caused by mutation in the LRP4 gene (OMIM ) on 11p12; CMS18 (OMIM ) is caused by mutation in the SNAP25 gene (OMIM ) on 20p11; CMS19 (OMIM ) is caused by mutation in the COL13A1 gene (OMIM ) on 10q22; CMS20 (OMIM ) is caused by mutation in the SLC5A7 gene (OMIM ) on 2q12; CMS21 (OMIM ) is caused by mutation in the SLC18A3 gene (OMIM ) on 10q11; and CMS22 (OMIM ) is caused by mutation in the PREPL gene (OMIM ) on 2p21.

Clinical Features

Top most frequent phenotypes and symptoms related to Myasthenic Syndrome, Congenital, 1a, Slow-channel; Cms1a

  • Scoliosis
  • Muscle weakness
  • Ptosis
  • High palate
  • Feeding difficulties
  • Dysarthria
  • Skeletal muscle atrophy
  • Dysphagia
  • Myopathy
  • Pectus carinatum

And another 13 symptoms. If you need more information about this disease we can help you.

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Incidence and onset information

— Currently we don't have prevalence information about this disease (Not enough data available about incidence and published cases.)
No data available about the known clinical features onset.

Alternative names

Myasthenic Syndrome, Congenital, 1a, Slow-channel; Cms1a Is also known as cms iia, formerly, myasthenic syndrome, congenital, type iia, formerly, cms2a, formerly.

Researches and researchers

Currently, we don't have any information about doctors, researches or researchers related to this disease. Please contact us if you would like to appear here.


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Myasthenic Syndrome, Congenital, 1a, Slow-channel; Cms1a Recommended genes panels

Panel Name, Specifity and genes Tested/covered
Congenital Myasthenic Syndrome Advanced Sequencing Evaluation.

By Athena Diagnostics Inc (United States).

SCN4A, CHAT, CHRNA1, CHRNB1, CHRND, CHRNE, COLQ, DOK7, DPAGT1, AGRN, GFPT1, MUSK, RAPSN
Specificity
8 %
Genes
100 %
Non-immune Hydrops Panel.

By Greenwood Genetic Center Diagnostic Laboratories Greenwood Genetic Center (United States).

RIT1, RPL11, RPL35A, RPL5, RPS10, RPS17, RPS19, RPS24, RPS26, SEC23B, SLC17A5, BRAF, SMPD1, SOS1, SOS2, SOX18, UROS, CBL, SHOC2, ALG9 , (...)

View the complete list with 66 more genes
Specificity
2 %
Genes
100 %
Neuromuscular Disorders Panel.

By Greenwood Genetic Center Diagnostic Laboratories Greenwood Genetic Center (United States).

RYR1, BIN1, SCN4A, SGCA, SGCB, SGCD, SGCE, SGCG, SLC25A4, SUCLA2, SUCLG1, TWNK, TCAP, TIA1, TK2, TNNI2, TNNT1, TPM2, TPM3, MYOT , (...)

View the complete list with 124 more genes
Specificity
1 %
Genes
100 %
Congenital Contractures Panel.

By Greenwood Genetic Center Diagnostic Laboratories Greenwood Genetic Center (United States).

SKI, SLC18A3, TNNI2, TNNT3, TPM2, TPM3, UBA1, ZMPSTE24, ACTA1, ADGRG6, SLC5A7, KLHL41, FKBP10, NEK9, NALCN, CHAT, CHRNA1, CHRNB1, CHRND, CHRNE , (...)

View the complete list with 37 more genes
Specificity
2 %
Genes
100 %
Comprehensive Neuromuscular Panel.

By Knight Diagnostic Laboratories - Molecular Diagnostic Center Oregon Health & Science University (United States).

RYR1, RYR2, BIN1, SCN4A, SGCA, SGCB, SGCD, SGCE, SGCG, TCAP, TNNI2, TNNT1, TPM2, TPM3, MYOT, TTN, VCP, VRK1, ACTA1, CAPN3 , (...)

View the complete list with 59 more genes
Specificity
2 %
Genes
100 %
Neuromuscular Disorders Sequencing Panel.

By Genetic Services Laboratory University of Chicago (United States).

RYR1, BIN1, SCN4A, SGCA, SGCB, SGCD, SGCG, SNAP25, STIM1, SYT2, TCAP, TNNT1, TNXB, TPM2, TPM3, MYOT, TTN, VCP, ACTA1, RXYLT1 , (...)

View the complete list with 91 more genes
Specificity
1 %
Genes
100 %
Congenital Myasthenic Syndrome Sequencing Panel.

By Genetic Services Laboratory University of Chicago (United States).

SCN4A, SNAP25, SYT2, CHAT, CHRNA1, CHRNB1, CHRND, CHRNE, COL13A1, COLQ, ALG2, DOK7, ALG14, DPAGT1, PREPL, AGRN, GFPT1, LRP4, MUSK, RAPSN
Specificity
5 %
Genes
100 %
Congenital Myasthenic Syndrome Deletion/Duplication Panel.

By Genetic Services Laboratory University of Chicago (United States).

SCN4A, SNAP25, SYT2, CHAT, CHRNA1, CHRNB1, CHRND, CHRNE, COL13A1, COLQ, ALG2, DOK7, ALG14, DPAGT1, PREPL, AGRN, GFPT1, LRP4, MUSK, RAPSN
Specificity
5 %
Genes
100 %

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Sources and references

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OMIM Genetic Syndrome Finder

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