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Presynaptic congenital myasthenic syndrome

MedGen UID:
155651
•Concept ID:
C0751884
•
Disease or Syndrome
Synonym: Presynaptic congenital myasthenic syndromes
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal recessive inheritance (Orphanet)
Autosomal dominant inheritance (Orphanet)
 
Orphanet: ORPHA98914

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Presynaptic congenital myasthenic syndrome

Professional guidelines

PubMed

The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies.
Vanhaesebrouck AE, Beeson D
Curr Opin Neurol 2019 Oct;32(5):696-703. doi: 10.1097/WCO.0000000000000736. PMID: 31361628Free PMC Article
Effective Treatment With Albuterol in DOK7 Congenital Myasthenic Syndrome in Children.
Tsao CY
Pediatr Neurol 2016 Jan;54:85-7. Epub 2015 Nov 6 doi: 10.1016/j.pediatrneurol.2015.09.019. PMID: 26552645
Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment.
Engel AG, Shen XM, Selcen D, Sine SM
Lancet Neurol 2015 Apr;14(4):420-34. doi: 10.1016/S1474-4422(14)70201-7. PMID: 25792100Free PMC Article

Recent clinical studies

Etiology

Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome.
Salpietro V, Lin W, Delle Vedove A, Storbeck M, Liu Y, Efthymiou S, Manole A, Wiethoff S, Ye Q, Saggar A, McElreavey K, Krishnakumar SS; SYNAPS Study Group, Pitt M, Bello OD, Rothman JE, Basel-Vanagaite L, Hubshman MW, Aharoni S, Manzur AY, Wirth B, Houlden H
Ann Neurol 2017 Apr;81(4):597-603. Epub 2017 Mar 29 doi: 10.1002/ana.24905. PMID: 28253535Free PMC Article
Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy.
Nicole S, Chaouch A, Torbergsen T, Bauché S, de Bruyckere E, Fontenille MJ, Horn MA, van Ghelue M, Løseth S, Issop Y, Cox D, Müller JS, Evangelista T, Stålberg E, Ioos C, Barois A, Brochier G, Sternberg D, Fournier E, Hantaï D, Abicht A, Dusl M, Laval SH, Griffin H, Eymard B, Lochmüller H
Brain 2014 Sep;137(Pt 9):2429-43. Epub 2014 Jun 20 doi: 10.1093/brain/awu160. PMID: 24951643

Diagnosis

Variants of SLC18A3 leading to congenital myasthenic syndrome in two children with varying presentations.
Lamond A, Buckley D, O'Dea J, Turner L
BMJ Case Rep 2021 Jan 18;14(1) doi: 10.1136/bcr-2020-237799. PMID: 33462016Free PMC Article
Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome.
O'Grady GL, Verschuuren C, Yuen M, Webster R, Menezes M, Fock JM, Pride N, Best HA, Benavides Damm T, Turner C, Lek M, Engel AG, North KN, Clarke NF, MacArthur DG, Kamsteeg EJ, Cooper ST
Neurology 2016 Oct 4;87(14):1442-1448. Epub 2016 Sep 2 doi: 10.1212/WNL.0000000000003179. PMID: 27590285Free PMC Article

Therapy

Presynaptic congenital myasthenic syndrome due to three novel mutations in SLC5A7 encoding the sodium-dependant high-affinity choline transporter.
Rodríguez Cruz PM, Hughes I, Manzur A, Munot P, Ramdas S, Wright R, Breen C, Pitt M, Pagnamenta AT, Taylor JC, Palace J, Beeson D
Neuromuscul Disord 2021 Jan;31(1):21-28. Epub 2020 Oct 20 doi: 10.1016/j.nmd.2020.10.006. PMID: 33250374
Congenital myasthenic syndrome due to novel CHAT mutations in an ethnic kadazandusun family.
Tan JS, Ambang T, Ahmad-Annuar A, Rajahram GS, Wong KT, Goh KJ
Muscle Nerve 2016 May;53(5):822-6. Epub 2016 Mar 23 doi: 10.1002/mus.25037. PMID: 26789281
Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome.
Whittaker RG, Herrmann DN, Bansagi B, Hasan BA, Lofra RM, Logigian EL, Sowden JE, Almodovar JL, Littleton JT, Zuchner S, Horvath R, Lochmüller H
Neurology 2015 Dec 1;85(22):1964-71. Epub 2015 Oct 30 doi: 10.1212/WNL.0000000000002185. PMID: 26519543Free PMC Article

Prognosis

Variants of SLC18A3 leading to congenital myasthenic syndrome in two children with varying presentations.
Lamond A, Buckley D, O'Dea J, Turner L
BMJ Case Rep 2021 Jan 18;14(1) doi: 10.1136/bcr-2020-237799. PMID: 33462016Free PMC Article
Presynaptic congenital myasthenic syndrome due to three novel mutations in SLC5A7 encoding the sodium-dependant high-affinity choline transporter.
Rodríguez Cruz PM, Hughes I, Manzur A, Munot P, Ramdas S, Wright R, Breen C, Pitt M, Pagnamenta AT, Taylor JC, Palace J, Beeson D
Neuromuscul Disord 2021 Jan;31(1):21-28. Epub 2020 Oct 20 doi: 10.1016/j.nmd.2020.10.006. PMID: 33250374
A presynaptic congenital myasthenic syndrome attributed to a homozygous sequence variant in LAMA5.
Maselli RA, Arredondo J, Vázquez J, Chong JX, Bamshad MJ, Nickerson DA, Lara M, Ng F, Lo VL, Pytel P, McDonald CM
Ann N Y Acad Sci 2018 Feb;1413(1):119-125. Epub 2018 Jan 28 doi: 10.1111/nyas.13585. PMID: 29377152Free PMC Article
Presynaptic congenital myasthenic syndrome with a homozygous sequence variant in LAMA5 combines myopia, facial tics, and failure of neuromuscular transmission.
Maselli RA, Arredondo J, Vázquez J, Chong JX; University of Washington Center for Mendelian Genomics, Bamshad MJ, Nickerson DA, Lara M, Ng F, Lo VL, Pytel P, McDonald CM
Am J Med Genet A 2017 Aug;173(8):2240-2245. Epub 2017 May 25 doi: 10.1002/ajmg.a.38291. PMID: 28544784Free PMC Article

Clinical prediction guides

Adeno-Associated Virus Type 9-Mediated Gene Therapy of Choline Acetyltransferase-Deficient Mice.
Lin CV, Thomas CAD, Huynh TL, Wei DT, Young JN, Aivazian AS, McInnes A, Xu J, Cook SE, Vazquez J, Maselli RA
Hum Gene Ther 2024 Feb;35(3-4):123-131. doi: 10.1089/hum.2023.173. PMID: 38299967
A presynaptic congenital myasthenic syndrome attributed to a homozygous sequence variant in LAMA5.
Maselli RA, Arredondo J, Vázquez J, Chong JX, Bamshad MJ, Nickerson DA, Lara M, Ng F, Lo VL, Pytel P, McDonald CM
Ann N Y Acad Sci 2018 Feb;1413(1):119-125. Epub 2018 Jan 28 doi: 10.1111/nyas.13585. PMID: 29377152Free PMC Article
Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome.
Salpietro V, Lin W, Delle Vedove A, Storbeck M, Liu Y, Efthymiou S, Manole A, Wiethoff S, Ye Q, Saggar A, McElreavey K, Krishnakumar SS; SYNAPS Study Group, Pitt M, Bello OD, Rothman JE, Basel-Vanagaite L, Hubshman MW, Aharoni S, Manzur AY, Wirth B, Houlden H
Ann Neurol 2017 Apr;81(4):597-603. Epub 2017 Mar 29 doi: 10.1002/ana.24905. PMID: 28253535Free PMC Article
Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy.
Nicole S, Chaouch A, Torbergsen T, Bauché S, de Bruyckere E, Fontenille MJ, Horn MA, van Ghelue M, Løseth S, Issop Y, Cox D, Müller JS, Evangelista T, Stålberg E, Ioos C, Barois A, Brochier G, Sternberg D, Fournier E, Hantaï D, Abicht A, Dusl M, Laval SH, Griffin H, Eymard B, Lochmüller H
Brain 2014 Sep;137(Pt 9):2429-43. Epub 2014 Jun 20 doi: 10.1093/brain/awu160. PMID: 24951643
Congenital myasthenic syndrome due to a novel missense mutation in the gene encoding choline acetyltransferase.
Schmidt C, Abicht A, Krampfl K, Voss W, Stucka R, Mildner G, Petrova S, Schara U, Mortier W, Bufler J, Huebner A, Lochmüller H
Neuromuscul Disord 2003 Mar;13(3):245-51. doi: 10.1016/s0960-8966(02)00273-0. PMID: 12609506

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