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Congenital myasthenic syndrome 15(CMSWTA; CMS15)

MedGen UID:
864033
Concept ID:
C4015596
Disease or Syndrome
Synonym: Myasthenic syndrome, congenital, 15, without tubular aggregates
 
Gene (location): ALG14 (1p21.3)
 
Monarch Initiative: MONDO:0014542
OMIM®: 616227

Definition

Congenital myasthenic syndrome-15 is one of a heterogeneous group of disorders that arise from impaired signal transmission at the neuromuscular synapse and are characterized by fatigable muscle weakness (summary by Cossins et al., 2013). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). [from OMIM]

Clinical features

From HPO
Fatigable weakness
MedGen UID:
451076
Concept ID:
C0947912
Disease or Syndrome
A type of weakness that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
Multiple joint contractures
MedGen UID:
57633
Concept ID:
C0158118
Acquired Abnormality
Difficulty walking
MedGen UID:
86319
Concept ID:
C0311394
Finding
Reduced ability to walk (ambulate).
Frequent falls
MedGen UID:
163408
Concept ID:
C0850703
Finding
Increased jitter at single fiber EMG
MedGen UID:
866698
Concept ID:
C4021045
Finding
The variation in the time interval between the two action potentials of the same motor unit is called jitter. This term therefore applies to increased variability in the interval between successive action potentials of the same motor unit, which is measured by electromyography (EMG).
EMG: decremental response of compound muscle action potential to repetitive nerve stimulation
MedGen UID:
892749
Concept ID:
C4021728
Finding
A compound muscle action potential (CMAP) is a type of electromyography (EMG). CMAP refers to a group of almost simultaneous action potentials from several muscle fibers in the same area evoked by stimulation of the supplying motor nerve and are recorded as one multipeaked summated action potential. This abnormality refers to a greater than normal decrease in the amplitude during the course of the investigation.
Anti-acetylcholine receptor antibody positivity
MedGen UID:
868186
Concept ID:
C4022578
Finding
The presence of autoantibodies (immunoglobulins) in the blood circulation that react against ganglioside-monosialic acid (GM1), which is a type of glycosphingolipid with one sialic acid. GM1 is located on the outer layer of the plasma membrane, and plays a vital role in neurogenesis, nerve development, differentiation and repair after injury.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Professional guidelines

PubMed

McMacken G, Whittaker RG, Wake R, Lochmuller H, Horvath R
J Neurol 2023 Jun;270(6):3112-3119. Epub 2023 Mar 4 doi: 10.1007/s00415-023-11643-z. PMID: 36869887Free PMC Article
Tsao CY
Pediatr Neurol 2016 Jan;54:85-7. Epub 2015 Nov 6 doi: 10.1016/j.pediatrneurol.2015.09.019. PMID: 26552645
Witting N, Vissing J
JAMA Neurol 2014 Mar;71(3):350-4. doi: 10.1001/jamaneurol.2013.5590. PMID: 24425145

Recent clinical studies

Etiology

Hesami O, Ramezani M, Ghasemi A, Fatehi F, Okhovat AA, Ziaadini B, Kariminejad A, Nafissi S
Orphanet J Rare Dis 2024 Mar 12;19(1):113. doi: 10.1186/s13023-024-03116-x. PMID: 38475910Free PMC Article
O'Connor K, Spendiff S, Lochmüller H, Horvath R
Int J Mol Sci 2023 May 9;24(10) doi: 10.3390/ijms24108505. PMID: 37239850Free PMC Article
Hamasaki Y, Hamada R, Muramatsu M, Matsumoto S, Aya K, Ishikura K, Kaneko T, Iijima K
BMC Nephrol 2020 Aug 24;21(1):363. doi: 10.1186/s12882-020-02010-5. PMID: 32838745Free PMC Article
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article
Juel VC, Massey JM
Orphanet J Rare Dis 2007 Nov 6;2:44. doi: 10.1186/1750-1172-2-44. PMID: 17986328Free PMC Article

Diagnosis

Allen NM, O'Rahelly M, Eymard B, Chouchane M, Hahn A, Kearns G, Kim DS, Byun SY, Nguyen CE, Schara-Schmidt U, Kölbel H, Marina AD, Schneider-Gold C, Roefke K, Thieme A, Van den Bergh P, Avalos G, Álvarez-Velasco R, Natera-de Benito D, Cheng MHM, Chan WK, Wan HS, Thomas MA, Borch L, Lauzon J, Kornblum C, Reimann J, Mueller A, Kuntzer T, Norwood F, Ramdas S, Jacobson LW, Jie X, Fernandez-Garcia MA, Wraige E, Lim M, Lin JP, Claeys KG, Aktas S, Oskoui M, Hacohen Y, Masud A, Leite MI, Palace J, De Vivo D, Vincent A, Jungbluth H
Brain 2023 Oct 3;146(10):4233-4246. doi: 10.1093/brain/awad153. PMID: 37186601Free PMC Article
Gonzalez-Quereda L, Rodriguez MJ, Diaz-Manera J, Alonso-Perez J, Gallardo E, Nascimento A, Ortez C, Natera-de Benito D, Olive M, Gonzalez-Mera L, Munain AL, Zulaica M, Poza JJ, Jerico I, Torne L, Riera P, Milisenda J, Sanchez A, Garrabou G, Llano I, Madruga-Garrido M, Gallano P
Genes (Basel) 2020 May 11;11(5) doi: 10.3390/genes11050539. PMID: 32403337Free PMC Article
Ciafaloni E
Continuum (Minneap Minn) 2019 Dec;25(6):1767-1784. doi: 10.1212/CON.0000000000000800. PMID: 31794470
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article
Juel VC, Massey JM
Orphanet J Rare Dis 2007 Nov 6;2:44. doi: 10.1186/1750-1172-2-44. PMID: 17986328Free PMC Article

Therapy

Hesami O, Ramezani M, Ghasemi A, Fatehi F, Okhovat AA, Ziaadini B, Kariminejad A, Nafissi S
Orphanet J Rare Dis 2024 Mar 12;19(1):113. doi: 10.1186/s13023-024-03116-x. PMID: 38475910Free PMC Article
Hamasaki Y, Hamada R, Muramatsu M, Matsumoto S, Aya K, Ishikura K, Kaneko T, Iijima K
BMC Nephrol 2020 Aug 24;21(1):363. doi: 10.1186/s12882-020-02010-5. PMID: 32838745Free PMC Article
Ciafaloni E
Continuum (Minneap Minn) 2019 Dec;25(6):1767-1784. doi: 10.1212/CON.0000000000000800. PMID: 31794470
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article
Tsao CY
Pediatr Neurol 2016 Jan;54:85-7. Epub 2015 Nov 6 doi: 10.1016/j.pediatrneurol.2015.09.019. PMID: 26552645

Prognosis

Hyde LF, Kong Y, Zhao L, Rao SR, Wang J, Stone L, Njaa A, Collin GB, Krebs MP, Chang B, Fliesler SJ, Nishina PM, Naggert JK
Int J Mol Sci 2022 Oct 9;23(19) doi: 10.3390/ijms231912005. PMID: 36233305Free PMC Article
Yang K, Cheng H, Yuan F, Meng L, Yin R, Zhang Y, Wang S, Wang C, Lu Y, Xi J, Lu Q, Chen Y
Medicine (Baltimore) 2018 Apr;97(17):e0347. doi: 10.1097/MD.0000000000010347. PMID: 29702980Free PMC Article
Luan X, Tian W, Cao L
Clin Neurol Neurosurg 2016 Nov;150:41-45. Epub 2016 Aug 22 doi: 10.1016/j.clineuro.2016.08.021. PMID: 27588369
Lashley D, Palace J, Jayawant S, Robb S, Beeson D
Neurology 2010 May 11;74(19):1517-23. doi: 10.1212/WNL.0b013e3181dd43bf. PMID: 20458068Free PMC Article
Juel VC, Massey JM
Orphanet J Rare Dis 2007 Nov 6;2:44. doi: 10.1186/1750-1172-2-44. PMID: 17986328Free PMC Article

Clinical prediction guides

Prior DE, Cooper BA, Zhang B, Ghosh PS
Muscle Nerve 2021 May;63(5):751-757. Epub 2021 Feb 28 doi: 10.1002/mus.27208. PMID: 33604899
McMacken G, Whittaker RG, Evangelista T, Abicht A, Dusl M, Lochmüller H
J Neurol 2018 Jan;265(1):194-203. Epub 2017 Nov 30 doi: 10.1007/s00415-017-8689-3. PMID: 29189923Free PMC Article
Caggiano S, Khirani S, Verrillo E, Barnerias C, Amaddeo A, Gitiaux C, Thierry B, Desguerre I, Cutrera R, Fauroux B
Eur J Paediatr Neurol 2017 Nov;21(6):842-851. Epub 2017 Jul 21 doi: 10.1016/j.ejpn.2017.07.010. PMID: 28755803
Luan X, Tian W, Cao L
Clin Neurol Neurosurg 2016 Nov;150:41-45. Epub 2016 Aug 22 doi: 10.1016/j.clineuro.2016.08.021. PMID: 27588369
Witting N, Vissing J
JAMA Neurol 2014 Mar;71(3):350-4. doi: 10.1001/jamaneurol.2013.5590. PMID: 24425145

Recent systematic reviews

Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article

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