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Genetics Home Reference: your guide to understanding genetic conditions
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Congenital myasthenic syndrome

Reviewed November 2011

What is congenital myasthenic syndrome?

Congenital myasthenic syndrome is a group of conditions characterized by muscle weakness (myasthenia) that worsens with physical exertion. The muscle weakness typically begins in early childhood but can also appear in adolescence or adulthood. Facial muscles, including muscles that control the eyelids, muscles that move the eyes, and muscles used for chewing and swallowing, are most commonly affected. However, any of the muscles used for movement (skeletal muscles) can be affected in this condition. Due to muscle weakness, affected infants may have feeding difficulties. Development of motor skills such as crawling or walking may be delayed. The severity of the myasthenia varies greatly, with some people experiencing minor weakness and others having such severe weakness that they are unable to walk.

Some individuals have episodes of breathing problems that may be triggered by fevers or infection. Severely affected individuals may also experience short pauses in breathing (apnea) that can lead to a bluish appearance of the skin or lips (cyanosis).

How common is congenital myasthenic syndrome?

The prevalence of congenital myasthenic syndrome is unknown. At least 600 families with affected individuals have been described in the scientific literature.

What genes are related to congenital myasthenic syndrome?

Mutations in many genes can cause congenital myasthenic syndrome. Mutations in the CHRNE gene are responsible for more than half of all cases. A large number of cases are also caused by mutations in the RAPSN, CHAT, COLQ, and DOK7 genes. All of these genes provide instructions for producing proteins that are involved in the normal function of the neuromuscular junction. The neuromuscular junction is the area between the ends of nerve cells and muscle cells where signals are relayed to trigger muscle movement.

Gene mutations lead to changes in proteins that play a role in the function of the neuromuscular junction and disrupt signaling between the ends of nerve cells and muscle cells. Disrupted signaling between these cells results in an impaired ability to move skeletal muscles, muscle weakness, and delayed development of motor skills. The respiratory problems in congenital myasthenic syndrome result from impaired movement of the muscles of the chest wall and the muscle that separates the abdomen from the chest cavity (the diaphragm).

Mutations in other genes that provide instructions for proteins involved in neuromuscular signaling have been found to cause some cases of congenital myasthenic syndrome, although these mutations account for only a small number of cases. Some people with congenital myasthenic syndrome do not have an identified mutation in any of the genes known to be associated with this condition.

Related Gene(s)

Changes in these genes are associated with congenital myasthenic syndrome.

  • AGRN
  • CHAT
  • CHRNA1
  • CHRNB1
  • CHRND
  • CHRNE
  • COLQ
  • DOK7
  • GFPT1
  • MUSK
  • PLEC
  • RAPSN
  • SCN4A

How do people inherit congenital myasthenic syndrome?

This condition is most commonly inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Rarely, this condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Where can I find information about diagnosis or management of congenital myasthenic syndrome?

These resources address the diagnosis or management of congenital myasthenic syndrome and may include treatment providers.

  • Gene Review: Congenital Myasthenic Syndromes (http://www.ncbi.nlm.nih.gov/books/NBK1168/)
  • Genetic Testing Registry: Congenital myasthenic syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0751882)
  • Genetic Testing Registry: Congenital myasthenic syndrome, acetazolamide-responsive (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1850599)
  • Genetic Testing Registry: Endplate acetylcholinesterase deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1864233)
  • Genetic Testing Registry: Familial infantile myasthenia (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0393929)
  • Genetic Testing Registry: Myasthenia, limb-girdle, familial (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1850792)
  • Genetic Testing Registry: Myasthenia, limb-girdle, with tubular aggregates (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1864649)
  • Genetic Testing Registry: Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1837091)
  • Genetic Testing Registry: Myasthenic syndrome, congenital, fast-channel (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1837122)
  • Genetic Testing Registry: Myasthenic syndrome, slow-channel congenital (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0751885)

You might also find information on the diagnosis or management of congenital myasthenic syndrome in Educational resources (http://ghr.nlm.nih.gov/condition/congenital-myasthenic-syndrome/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/congenital-myasthenic-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about congenital myasthenic syndrome?

You may find the following resources about congenital myasthenic syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for congenital myasthenic syndrome?

  • CMS
  • congenital myasthenia
  • congenital myasthenic syndromes

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about congenital myasthenic syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding congenital myasthenic syndrome?

apnea ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; congenital ; cyanosis ; gene ; infection ; inherited ; motor ; muscle cells ; mutation ; neuromuscular junction ; prevalence ; recessive ; respiratory ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Barišić N, Chaouch A, Müller JS, Lochmüller H. Genetic heterogeneity and pathophysiological mechanisms in congenital myasthenic syndromes. Eur J Paediatr Neurol. 2011 May;15(3):189-96. doi: 10.1016/j.ejpn.2011.03.006. Epub 2011 Apr 17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21498094?dopt=Abstract)
  • Beeson D, Webster R, Cossins J, Lashley D, Spearman H, Maxwell S, Slater CR, Newsom-Davis J, Palace J, Vincent A. Congenital myasthenic syndromes and the formation of the neuromuscular junction. Ann N Y Acad Sci. 2008;1132:99-103. doi: 10.1196/annals.1405.049. (http://www.ncbi.nlm.nih.gov/pubmed/18567858?dopt=Abstract)
  • Engel AG, Shen XM, Selcen D, Sine SM. What have we learned from the congenital myasthenic syndromes. J Mol Neurosci. 2010 Jan;40(1-2):143-53. doi: 10.1007/s12031-009-9229-0. Epub 2009 Aug 18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19688192?dopt=Abstract)
  • Engel AG. Current status of the congenital myasthenic syndromes. Neuromuscul Disord. 2012 Feb;22(2):99-111. doi: 10.1016/j.nmd.2011.10.009. Epub 2011 Nov 21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22104196?dopt=Abstract)
  • Kinali M, Beeson D, Pitt MC, Jungbluth H, Simonds AK, Aloysius A, Cockerill H, Davis T, Palace J, Manzur AY, Jimenez-Mallebrera C, Sewry C, Muntoni F, Robb SA. Congenital myasthenic syndromes in childhood: diagnostic and management challenges. J Neuroimmunol. 2008 Sep 15;201-202:6-12. doi: 10.1016/j.jneuroim.2008.06.026. Epub 2008 Aug 15. (http://www.ncbi.nlm.nih.gov/pubmed/18707767?dopt=Abstract)
  • Senderek J, Müller JS, Dusl M, Strom TM, Guergueltcheva V, Diepolder I, Laval SH, Maxwell S, Cossins J, Krause S, Muelas N, Vilchez JJ, Colomer J, Mallebrera CJ, Nascimento A, Nafissi S, Kariminejad A, Nilipour Y, Bozorgmehr B, Najmabadi H, Rodolico C, Sieb JP, Steinlein OK, Schlotter B, Schoser B, Kirschner J, Herrmann R, Voit T, Oldfors A, Lindbergh C, Urtizberea A, von der Hagen M, Hübner A, Palace J, Bushby K, Straub V, Beeson D, Abicht A, Lochmüller H. Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. Am J Hum Genet. 2011 Feb 11;88(2):162-72. doi: 10.1016/j.ajhg.2011.01.008. (http://www.ncbi.nlm.nih.gov/pubmed/21310273?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2011
Published: September 1, 2014