Humanities
Skip to main content Skip to main navigation menu Skip to site footer
  • Register
  • Login
  • Menu
  • Home
  • Current
  • Archives
  • Announcements
  • About
    • About the Journal
    • Submissions
    • Editorial Team
    • Privacy Statement
    • Contact
  • Register
  • Login

Journal of Education, Health and Sport

Congenital myasthenic syndromes (CMS) a rare cause of uncommon fatigue
  • Home
  • /
  • Congenital myasthenic syndromes (CMS) a rare cause of uncommon fatigue
  1. Home /
  2. Archives /
  3. Vol. 13 No. 2 (2023) /
  4. Articles

Congenital myasthenic syndromes (CMS) a rare cause of uncommon fatigue

Authors

  • Jan Lejman Student Scientific Society, Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin https://orcid.org/0000-0002-8065-2839
  • Kinga Panuciak Student Scientific Society, Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, A. Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0000-0001-9014-5171
  • Emilia Nowicka Student Scientific Society, Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, A. Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0000-0002-2743-1551
  • Angelika Mastalerczyk Student Scientific Society, Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, A. Racławickie 1, 20-059 Lublin, Poland; 2. Student Scientific Society ISOMERS, Department of Medicinal Chemistry, Medical University of Lublin, Chodźki Street 4A, 20-093 Lublin, Poland https://orcid.org/0000-0002-7576-2152
  • Karolina Makowska Student Scientific Society, Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, A. Racławickie 1, 20-059 Lublin, Poland https://orcid.org/0000-0001-5467-3137
  • Michał Obel Student Scientific Association at the Department of Endocrinology, Medical University of Lublin, Chodźki Street 19, 20-093 Lublin, Poland https://orcid.org/0000-0003-1237-8732
  • Kamila Czyżak Student Scientific Association at the Department of Endocrinology, Medical University of Lublin, Chodźki Street 19, 20-093 Lublin, Poland https://orcid.org/0000-0002-8866-5810
  • Wiktor Wiśniewski EMC Clinic, Łowiecka Street 24, 50-220 Wrocław, Poland https://orcid.org/0000-0001-5845-8012

DOI:

https://doi.org/10.12775/JEHS.2023.13.02.004

Keywords

congenital myasthenic syndromes, neuromuscular disease, weakness, inheritance

Abstract

Introduction and purpose:

Muscle weakness in newborns, infants and young children can be caused by disorders of the neuromuscular junction (NMJ). Congenital myasthenic syndromes (CMS) are a group of rare genetic diseases whose symptoms resemble the clinical picture of autoimmune myasthenia gravis. There are many mutations that can disrupt the neuromuscular transmission leading to pathology. The diagnosis of CMS is based on genetic testing. The aim of this study is to draw clinicians' attention to the symptoms and present current forms of CMS diagnosis and management.

State of knowledge:

An increasing number of genetic changes are associated with CMS pathology. They are divided, depending on the location in the NMJ of the encoded protein, into presynaptic, synaptic and postsynaptic. The most common disorder is the mutation of CHRNE, which is responsible for the expression of one of the subunits in the structure of the acetylcholine receptor. Regardless of the type of disease, the characteristic symptom is uncommon fatigue of skeletal muscles. It may present as ptosis of one or both eyelids or gait disturbance. The interview, laboratory tests and EMG are helpful in the diagnosis, but genetic tests play a key role. They can target specific mutations or cover the entire genome comprehensively. Currently used drugs alleviate the course of CMS by increasing the release of acetylcholine or increasing the concentration of acetylcholine in the synaptic cleft.

Conclusion:

Because of its rarity and variability, many CMS patients may be misdiagnosed. It is important to implement extensive genetic diagnostics and early implementation of treatment. There is a need for long-term studies of CMS cases and implementation of therapies targeted at specific mutations.

References

Rodríguez Cruz, P. M., Palace, J., & Beeson, D. (2018). The Neuromuscular Junction and Wide Heterogeneity of Congenital Myasthenic Syndromes. International journal of molecular sciences, 19(6), 1677. https://doi.org/10.3390/ijms19061677

Troha Gergeli, A., Neubauer, D., Golli, T., Butenko, T., Loboda, T., Maver, A., & Osredkar, D. (2020). Prevalence and genetic subtypes of congenital myasthenic syndromes in the pediatric population of Slovenia. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 26, 34–38. https://doi.org/10.1016/j.ejpn.2020.02.002

Krenn, M., Sener, M., Rath, J., Zulehner, G., Keritam, O., Wagner, M., Laccone, F., Iglseder, S., Marte, S., Baumgartner, M., Eisenkölbl, A., Liechtenstein, C., Rudnik, S., Quasthoff, S., Grinzinger, S., Spenger, J., Wortmann, S. B., Löscher, W. N., Zimprich, F., Kellersmann, A., … Cetin, H. (2022). The clinical and molecular landscape of congenital myasthenic syndromes in Austria: a nationwide study. Journal of neurology, 10.1007/s00415-022-11440-0. Advance online publication. https://doi.org/10.1007/s00415-022-11440-0

Della Marina, A., Wibbeler, E., Abicht, A., Kölbel, H., Lochmüller, H., Roos, A., & Schara, U. (2020). Long Term Follow-Up on Pediatric Cases With Congenital Myasthenic Syndromes-A Retrospective Single Centre Cohort Study. Frontiers in human neuroscience, 14, 560860. https://doi.org/10.3389/fnhum.2020.560860

Abicht, A., Müller, J. S., & Lochmüller, H. (2003). Congenital Myasthenic Syndromes Overview. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle.

Vanhaesebrouck, A. E., & Beeson, D. (2019). The congenital myasthenic syndromes: expanding genetic and phenotypic spectrums and refining treatment strategies. Current opinion in neurology, 32(5), 696–703. https://doi.org/10.1097/WCO.0000000000000736

Zhang, Y., Cheng, X., Luo, C., Lei, M., Mao, F., Shi, Z., Cao, W., Zhang, J., & Zhang, Q. (2020). Congenital Myasthenic Syndrome Caused by a Novel Hemizygous CHAT Mutation. Frontiers in pediatrics, 8, 185. https://doi.org/10.3389/fped.2020.00185

English, B. A., Hahn, M. K., Gizer, I. R., Mazei-Robison, M., Steele, A., Kurnik, D. M., Stein, M. A., Waldman, I. D., & Blakely, R. D. (2009). Choline transporter gene variation is associated with attention-deficit hyperactivity disorder. Journal of neurodevelopmental disorders, 1(4), 252–263. https://doi.org/10.1007/s11689-009-9033-8

Finsterer J. (2019). Congenital myasthenic syndromes. Orphanet journal of rare diseases, 14(1), 57. https://doi.org/10.1186/s13023-019-1025-5

Aran, A., Segel, R., Kaneshige, K., Gulsuner, S., Renbaum, P., Oliphant, S., Meirson, T., Weinberg-Shukron, A., Hershkovitz, Y., Zeligson, S., Lee, M. K., Samson, A. O., Parsons, S. M., King, M. C., Levy-Lahad, E., & Walsh, T. (2017). Vesicular acetylcholine transporter defect underlies devastating congenital myasthenia syndrome. Neurology, 88(11), 1021–1028. https://doi.org/10.1212/WNL.0000000000003720

Shen, X. M., Selcen, D., Brengman, J., & Engel, A. G. (2014). Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability. Neurology, 83(24), 2247–2255. https://doi.org/10.1212/WNL.0000000000001079

Salpietro, V., Lin, W., Delle Vedove, A., Storbeck, M., Liu, Y., Efthymiou, S., Manole, A., Wiethoff, S., Ye, Q., Saggar, A., McElreavey, K., Krishnakumar, S. S., SYNAPS Study Group, Pitt, M., Bello, O. D., Rothman, J. E., Basel-Vanagaite, L., Hubshman, M. W., Aharoni, S., Manzur, A. Y., … Houlden, H. (2017). Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome. Annals of neurology, 81(4), 597–603. https://doi.org/10.1002/ana.24905

Shen, X. M., Scola, R. H., Lorenzoni, P. J., Kay, C. S., Werneck, L. C., Brengman, J., Selcen, D., & Engel, A. G. (2017). Novel synaptobrevin-1 mutation causes fatal congenital myasthenic syndrome. Annals of clinical and translational neurology, 4(2), 130–138. https://doi.org/10.1002/acn3.387

Fionda, L., Turon-Sans, J., Fuentes Prior, P., Bernal Noguera, S., Cortés-Vicente, E., López-Pérez, M. A., Gallardo, E., & Rojas-García, R. (2021). A new de novo SYT2 mutation presenting as distal weakness. Neuropathy or neuromuscular junction dysfunction?. Journal of the peripheral nervous system : JPNS, 26(1), 113–117. https://doi.org/10.1111/jns.12425

Engel, A. G., Selcen, D., Shen, X. M., Milone, M., & Harper, C. M. (2016). Loss of MUNC13-1 function causes microcephaly, cortical hyperexcitability, and fatal myasthenia. Neurology. Genetics, 2(5), e105. https://doi.org/10.1212/NXG.0000000000000105

Régal, L., Shen, X. M., Selcen, D., Verhille, C., Meulemans, S., Creemers, J. W., & Engel, A. G. (2014). PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome. Neurology, 82(14), 1254–1260. https://doi.org/10.1212/WNL.0000000000000295

Krejci, E., Thomine, S., Boschetti, N., Legay, C., Sketelj, J., & Massoulié, J. (1997). The mammalian gene of acetylcholinesterase-associated collagen. The Journal of biological chemistry, 272(36), 22840–22847. https://doi.org/10.1074/jbc.272.36.22840

Ito, M., & Ohno, K. (2018). Protein-anchoring therapy to target extracellular matrix proteins to their physiological destinations. Matrix biology : journal of the International Society for Matrix Biology, 68-69, 628–636. https://doi.org/10.1016/j.matbio.2018.02.014

Ohno, K., Brengman, J., Tsujino, A., & Engel, A. G. (1998). Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme. Proceedings of the National Academy of Sciences of the United States of America, 95(16), 9654–9659. https://doi.org/10.1073/pnas.95.16.9654

Legay C. (2018). Congenital myasthenic syndromes with acetylcholinesterase deficiency, the pathophysiological mechanisms. Annals of the New York Academy of Sciences, 1413(1), 104–110. https://doi.org/10.1111/nyas.13595

Maselli, R. A., Arredondo, J., Vázquez, J., Chong, J. X., Bamshad, M. J., Nickerson, D. A., Lara, M., Ng, F., Lo, V. L., Pytel, P., & McDonald, C. M. (2018). A presynaptic congenital myasthenic syndrome attributed to a homozygous sequence variant in LAMA5. Annals of the New York Academy of Sciences, 1413(1), 119–125. https://doi.org/10.1111/nyas.13585

Maselli, R. A., Ng, J. J., Anderson, J. A., Cagney, O., Arredondo, J., Williams, C., Wessel, H. B., Abdel-Hamid, H., & Wollmann, R. L. (2009). Mutations in LAMB2 causing a severe form of synaptic congenital myasthenic syndrome. Journal of medical genetics, 46(3), 203–208. https://doi.org/10.1136/jmg.2008.063693

Logan, C. V., Cossins, J., Rodríguez Cruz, P. M., Parry, D. A., Maxwell, S., Martínez-Martínez, P., Riepsaame, J., Abdelhamed, Z. A., Lake, A. V., Moran, M., Robb, S., Chow, G., Sewry, C., Hopkins, P. M., Sheridan, E., Jayawant, S., Palace, J., Johnson, C. A., & Beeson, D. (2015). Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain. American journal of human genetics, 97(6), 878–885. https://doi.org/10.1016/j.ajhg.2015.10.017

Lorenzoni, P. J., Scola, R. H., Kay, C. S., & Werneck, L. C. (2012). Congenital myasthenic syndrome: a brief review. Pediatric neurology, 46(3), 141–148. https://doi.org/10.1016/j.pediatrneurol.2011.12.001

Gómez-García de la Banda, M., Simental-Aldaba, E., Fahmy, N., Sternberg, D., Blondy, P., Quijano-Roy, S., & Malfatti, E. (2022). Case Report: A Novel AChR Epsilon Variant Causing a Clinically Discordant Salbutamol Responsive Congenital Myasthenic Syndrome in Two Egyptian Siblings. Frontiers in neurology, 13, 909715. https://doi.org/10.3389/fneur.2022.909715

Engel A. G. (2018). Genetic basis and phenotypic features of congenital myasthenic syndromes. Handbook of clinical neurology, 148, 565–589. https://doi.org/10.1016/B978-0-444-64076-5.00037-5

Estephan, E. P., Zambon, A. A., Marchiori, P. E., da Silva, A. M. S., Caldas, V. M., Moreno, C. A. M., Reed, U. C., Horvath, R., Töpf, A., Lochmüller, H., & Zanoteli, E. (2018). Clinical variability of early-onset congenital myasthenic syndrome due to biallelic RAPSN mutations in Brazil. Neuromuscular disorders : NMD, 28(11), 961–964. https://doi.org/10.1016/j.nmd.2018.08.007

Oury, J., Zhang, W., Leloup, N., Koide, A., Corrado, A. D., Ketavarapu, G., Hattori, T., Koide, S., & Burden, S. J. (2021). Mechanism of disease and therapeutic rescue of Dok7 congenital myasthenia. Nature, 595(7867), 404–408. https://doi.org/10.1038/s41586-021-03672-3

Engel, A. G., Shen, X. M., Selcen, D., & Sine, S. (2012). New horizons for congenital myasthenic syndromes. Annals of the New York Academy of Sciences, 1275(1), 54–62. https://doi.org/10.1111/j.1749-6632.2012.06803.x

Jacquier, A., Risson, V., Simonet, T., Roussange, F., Lacoste, N., Ribault, S., Carras, J., Theuriet, J., Girard, E., Grosjean, I., Le Goff, L., Kröger, S., Meltoranta, J., Bauché, S., Sternberg, D., Fournier, E., Kostera-Pruszczyk, A., O'Connor, E., Eymard, B., Lochmüller, H., … Schaeffer, L. (2022). Severe congenital myasthenic syndromes caused by agrin mutations affecting secretion by motoneurons. Acta neuropathologica, 144(4), 707–731. https://doi.org/10.1007/s00401-022-02475-8

Heckmann, J. M., Europa, T. A., Soni, A. J., & Nel, M. (2022). The Epidemiology and Phenotypes of Ocular Manifestations in Childhood and Juvenile Myasthenia Gravis: A Review. Frontiers in neurology, 13, 834212. https://doi.org/10.3389/fneur.2022.834212

Angelini, C., Giaretta, L., & Marozzo, R. (2018). An update on diagnostic options and considerations in limb-girdle dystrophies. Expert review of neurotherapeutics, 18(9), 693–703. https://doi.org/10.1080/14737175.2018.1508997

Kondo, H., Tsuji, Y., Lee, T., Saito, Y., & Nishino, I. (2022). Severe congenital myasthenic syndrome with novel variants in the CHRND gene. Pediatrics international : official journal of the Japan Pediatric Society, 64(1), e15342. https://doi.org/10.1111/ped.15342

Rodríguez Cruz, P. M., Cossins, J., Estephan, E. P., Munell, F., Selby, K., Hirano, M., Maroofin, R., Mehrjardi, M. Y. V., Chow, G., Carr, A., Manzur, A., Robb, S., Munot, P., Wei Liu, W., Banka, S., Fraser, H., De Goede, C., Zanoteli, E., Conti Reed, U., Sage, A., … Beeson, D. (2019). The clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutations. Brain : a journal of neurology, 142(6), 1547–1560. https://doi.org/10.1093/brain/awz107

Cimpoca-Raptis, B. A., Ciobanu, A. M., Gica, N., Peltecu, G., Mitrea, D., & Panaitescu, A. M. (2021). Fetal Surveillance in Pregnancies with Myasthenia Gravis. Medicina (Kaunas, Lithuania), 57(11), 1277. https://doi.org/10.3390/medicina57111277

Qashqari, H., McNiven, V., Gonorazky, H., Mendoza-Londono, R., Hassan, A., Kulkarni, T., Amburgey, K., & Dowling, J. J. (2022). PURA syndrome: neuromuscular junction manifestations with potential therapeutic implications. Neuromuscular disorders : NMD, 32(10), 842–844. https://doi.org/10.1016/j.nmd.2022.09.007

Engel, A. G., Shen, X. M., & Selcen, D. (2018). The unfolding landscape of the congenital myasthenic syndromes. Annals of the New York Academy of Sciences, 1413(1), 25–34. https://doi.org/10.1111/nyas.13539

Caldas, V. M., Heise, C. O., Kouyoumdjian, J. A., Zambon, A. A., Silva, A. M. S., Estephan, E. P., & Zanoteli, E. (2020). Electrophysiological study of neuromuscular junction in congenital myasthenic syndromes, congenital myopathies, and chronic progressive external ophthalmoplegia. Neuromuscular disorders : NMD, 30(11), 897–903. https://doi.org/10.1016/j.nmd.2020.10.002

Engel, A. G., Shen, X. M., Selcen, D., & Sine, S. M. (2015). Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. The Lancet. Neurology, 14(5), 461. https://doi.org/10.1016/S1474-4422(15)00010-1

Huang, K., Luo, Y. B., Bi, F. F., & Yang, H. (2021). Pharmacological Strategy for Congenital Myasthenic Syndrome with CHRNE Mutations: A Meta-Analysis of Case Reports. Current neuropharmacology, 19(5), 718–729. https://doi.org/10.2174/1570159X18666200729092332

Kao, J. C., Milone, M., Selcen, D., Shen, X. M., Engel, A. G., & Liewluck, T. (2018). Congenital myasthenic syndromes in adult neurology clinic: A long road to diagnosis and therapy. Neurology, 91(19), e1770–e1777. https://doi.org/10.1212/WNL.0000000000006478

Lee, M., Beeson, D., & Palace, J. (2018). Therapeutic strategies for congenital myasthenic syndromes. Annals of the New York Academy of Sciences, 1412(1), 129–136. https://doi.org/10.1111/nyas.13538

McMacken, G. M., Spendiff, S., Whittaker, R. G., O'Connor, E., Howarth, R. M., Boczonadi, V., Horvath, R., Slater, C. R., & Lochmüller, H. (2019). Salbutamol modifies the neuromuscular junction in a mouse model of ColQ myasthenic syndrome. Human molecular genetics, 28(14), 2339–2351. https://doi.org/10.1093/hmg/ddz059

Bestue-Cardiel, M., Sáenz de Cabezón-Alvarez, A., Capablo-Liesa, J. L., López-Pisón, J., Peña-Segura, J. L., Martin-Martinez, J., & Engel, A. G. (2005). Congenital endplate acetylcholinesterase deficiency responsive to ephedrine. Neurology, 65(1), 144–146. https://doi.org/10.1212/01.wnl.0000167132.35865.31

Lee, M., Beeson, D., & Palace, J. (2018). Therapeutic strategies for congenital myasthenic syndromes. Annals of the New York Academy of Sciences, 1412(1), 129–136. https://doi.org/10.1111/nyas.13538

Downloads

  • PDF

Published

2022-12-09

How to Cite

1.
LEJMAN, Jan, PANUCIAK, Kinga, NOWICKA, Emilia, MASTALERCZYK, Angelika, MAKOWSKA, Karolina, OBEL, Michał, CZYŻAK, Kamila and WIŚNIEWSKI, Wiktor. Congenital myasthenic syndromes (CMS) a rare cause of uncommon fatigue. Journal of Education, Health and Sport. Online. 9 December 2022. Vol. 13, no. 2, pp. 31-36. [Accessed 3 July 2025]. DOI 10.12775/JEHS.2023.13.02.004.
  • ISO 690
  • ACM
  • ACS
  • APA
  • ABNT
  • Chicago
  • Harvard
  • IEEE
  • MLA
  • Turabian
  • Vancouver
Download Citation
  • Endnote/Zotero/Mendeley (RIS)
  • BibTeX

Issue

Vol. 13 No. 2 (2023)

Section

Articles

License

Copyright (c) 2022 Jan Lejman, Kinga Panuciak, Emilia Nowicka, Angelika Mastalerczyk, Karolina Makowska, Michał Obel, Kamila Czyżak, Wiktor Wiśniewski

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0

Stats

Number of views and downloads: 719
Number of citations: 0

Search

Search

Browse

  • Browse Author Index
  • Issue archive

User

User

Current Issue

  • Atom logo
  • RSS2 logo
  • RSS1 logo

Information

  • For Readers
  • For Authors
  • For Librarians

Newsletter

Subscribe Unsubscribe

Tags

Search using one of provided tags:

congenital myasthenic syndromes, neuromuscular disease, weakness, inheritance
Up

Akademicka Platforma Czasopism

Najlepsze czasopisma naukowe i akademickie w jednym miejscu

apcz.umk.pl

Partners

  • Akademia Ignatianum w Krakowie
  • Akademickie Towarzystwo Andragogiczne
  • Fundacja Copernicus na rzecz Rozwoju Badań Naukowych
  • Instytut Historii im. Tadeusza Manteuffla Polskiej Akademii Nauk
  • Instytut Kultur Śródziemnomorskich i Orientalnych PAN
  • Instytut Tomistyczny
  • Karmelitański Instytut Duchowości w Krakowie
  • Ministerstwo Kultury i Dziedzictwa Narodowego
  • Państwowa Akademia Nauk Stosowanych w Krośnie
  • Państwowa Akademia Nauk Stosowanych we Włocławku
  • Państwowa Wyższa Szkoła Zawodowa im. Stanisława Pigonia w Krośnie
  • Polska Fundacja Przemysłu Kosmicznego
  • Polskie Towarzystwo Ekonomiczne
  • Polskie Towarzystwo Ludoznawcze
  • Towarzystwo Miłośników Torunia
  • Towarzystwo Naukowe w Toruniu
  • Uniwersytet im. Adama Mickiewicza w Poznaniu
  • Uniwersytet Komisji Edukacji Narodowej w Krakowie
  • Uniwersytet Mikołaja Kopernika
  • Uniwersytet w Białymstoku
  • Uniwersytet Warszawski
  • Wojewódzka Biblioteka Publiczna - Książnica Kopernikańska
  • Wyższe Seminarium Duchowne w Pelplinie / Wydawnictwo Diecezjalne „Bernardinum" w Pelplinie

© 2021- Nicolaus Copernicus University Accessibility statement Shop