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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
Gait disturbance
MedGen UID:
107895
•Concept ID:
C0575081
•
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Multiple joint contractures
MedGen UID:
57633
•Concept ID:
C0158118
•
Acquired Abnormality
See: Search on this feature
Frequent falls
MedGen UID:
163408
•Concept ID:
C0850703
•
Finding
See: Feature record | Search on this feature
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).
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Anti-neuromuscular Junction acetylcholine receptor antibody positivity
MedGen UID:
1055518
•Concept ID:
CN378840
•
Finding
The presence of autoantibodies (immunoglobulins) in the blood circulation that react against neuromuscular junction acetylcholine receptors.
See: Feature record | Search on this feature
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).
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Neuromuscular junction involvement in inherited motor neuropathies: genetic heterogeneity and effect of oral salbutamol treatment.
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
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
Pharmacologic treatment of downstream of tyrosine kinase 7 congenital myasthenic syndrome.
Witting N, Vissing J
JAMA Neurol 2014 Mar;71(3):350-4. doi: 10.1001/jamaneurol.2013.5590. PMID: 24425145

Recent clinical studies

Etiology

Congenital myasthenic syndromes in adults: clinical features, diagnosis and long-term prognosis.
Theuriet J, Masingue M, Behin A, Ferreiro A, Bassez G, Jaubert P, Tarabay O, Fer F, Pegat A, Bouhour F, Svahn J, Petiot P, Jomir L, Chauplannaz G, Cornut-Chauvinc C, Manel V, Salort-Campana E, Attarian S, Fortanier E, Verschueren A, Kouton L, Camdessanché JP, Tard C, Magot A, Péréon Y, Noury JB, Minot-Myhie MC, Perie M, Taithe F, Farhat Y, Millet AL, Cintas P, Solé G, Spinazzi M, Esselin F, Renard D, Sacconi S, Ezaru A, Malfatti E, Mallaret M, Magy L, Diab E, Merle P, Michaud M, Fournier M, Pakleza AN, Chanson JB, Lefeuvre C, Laforet P, Richard P, Sternberg D, Villar-Quiles RN, Stojkovic T, Eymard B
Brain 2024 Nov 4;147(11):3849-3862. doi: 10.1093/brain/awae124. PMID: 38696726Free PMC Article
Rare disease research workflow using multilayer networks elucidates the molecular determinants of severity in Congenital Myasthenic Syndromes.
Núñez-Carpintero I, Rigau M, Bosio M, O'Connor E, Spendiff S, Azuma Y, Topf A, Thompson R, 't Hoen PAC, Chamova T, Tournev I, Guergueltcheva V, Laurie S, Beltran S, Capella-Gutiérrez S, Cirillo D, Lochmüller H, Valencia A
Nat Commun 2024 Feb 28;15(1):1227. doi: 10.1038/s41467-024-45099-0. PMID: 38418480Free PMC Article
Congenital myasthenic syndromes.
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article
Genetic heterogeneity and pathophysiological mechanisms in congenital myasthenic syndromes.
Barišić N, Chaouch A, Müller JS, Lochmüller H
Eur J Paediatr Neurol 2011 May;15(3):189-96. Epub 2011 Apr 17 doi: 10.1016/j.ejpn.2011.03.006. PMID: 21498094
Myasthenia gravis.
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

Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain.
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
Myasthenia Gravis and Congenital Myasthenic Syndromes.
Ciafaloni E
Continuum (Minneap Minn) 2019 Dec;25(6):1767-1784. doi: 10.1212/CON.0000000000000800. PMID: 31794470
Congenital myasthenic syndromes.
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article
Genetic heterogeneity and pathophysiological mechanisms in congenital myasthenic syndromes.
Barišić N, Chaouch A, Müller JS, Lochmüller H
Eur J Paediatr Neurol 2011 May;15(3):189-96. Epub 2011 Apr 17 doi: 10.1016/j.ejpn.2011.03.006. PMID: 21498094
Myasthenia gravis.
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

COLQ-Congenital myasthenic syndrome in an Iranian cohort: the clinical and genetics spectrum.
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
A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan.
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
Myasthenia Gravis and Congenital Myasthenic Syndromes.
Ciafaloni E
Continuum (Minneap Minn) 2019 Dec;25(6):1767-1784. doi: 10.1212/CON.0000000000000800. PMID: 31794470
Congenital myasthenic syndromes.
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free 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

Prognosis

Congenital myasthenic syndromes in adults: clinical features, diagnosis and long-term prognosis.
Theuriet J, Masingue M, Behin A, Ferreiro A, Bassez G, Jaubert P, Tarabay O, Fer F, Pegat A, Bouhour F, Svahn J, Petiot P, Jomir L, Chauplannaz G, Cornut-Chauvinc C, Manel V, Salort-Campana E, Attarian S, Fortanier E, Verschueren A, Kouton L, Camdessanché JP, Tard C, Magot A, Péréon Y, Noury JB, Minot-Myhie MC, Perie M, Taithe F, Farhat Y, Millet AL, Cintas P, Solé G, Spinazzi M, Esselin F, Renard D, Sacconi S, Ezaru A, Malfatti E, Mallaret M, Magy L, Diab E, Merle P, Michaud M, Fournier M, Pakleza AN, Chanson JB, Lefeuvre C, Laforet P, Richard P, Sternberg D, Villar-Quiles RN, Stojkovic T, Eymard B
Brain 2024 Nov 4;147(11):3849-3862. doi: 10.1093/brain/awae124. PMID: 38696726Free PMC Article
CHRNE compound heterozygous mutations in congenital myasthenic syndrome: A case report.
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
Limb-girdle congenital myasthenic syndrome in a Chinese family with novel mutations in MUSK gene and literature review.
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
Long-term follow-up of patients with congenital myasthenic syndrome caused by COLQ mutations.
Wargon I, Richard P, Kuntzer T, Sternberg D, Nafissi S, Gaudon K, Lebail A, Bauche S, Hantaï D, Fournier E, Eymard B, Stojkovic T
Neuromuscul Disord 2012 Apr;22(4):318-24. Epub 2011 Nov 15 doi: 10.1016/j.nmd.2011.09.002. PMID: 22088788
Myasthenia gravis.
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

Developing outcome measures of disease activity in pediatric myasthenia.
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
Congenital myasthenic syndrome with episodic apnoea: clinical, neurophysiological and genetic features in the long-term follow-up of 19 patients.
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
Sleep in infants with congenital myasthenic syndromes.
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
Pharmacologic treatment of downstream of tyrosine kinase 7 congenital myasthenic syndrome.
Witting N, Vissing J
JAMA Neurol 2014 Mar;71(3):350-4. doi: 10.1001/jamaneurol.2013.5590. PMID: 24425145
Implications of the quaternary twist allosteric model for the physiology and pathology of nicotinic acetylcholine receptors.
Taly A, Corringer PJ, Grutter T, Prado de Carvalho L, Karplus M, Changeux JP
Proc Natl Acad Sci U S A 2006 Nov 7;103(45):16965-70. Epub 2006 Oct 31 doi: 10.1073/pnas.0607477103. PMID: 17077146Free PMC Article

Recent systematic reviews

Congenital myasthenic syndromes.
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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