Congenital myasthenic syndromes

What is the cause of congenital myasthenic syndromes?

Congenital myasthenic syndromes are caused by genetic changes in at least 32 genes. Each gene is associated with a different subtype. The most common genes involved are CHAT, COLQ , RAPSN , CHRNE , DOK7 , and GFPT1. Many of the other genes that cause CMS are found in only a few families or individuals.

Last updated on 05-01-20

How might congenital myasthenic syndromes be diagnosed?

Congenital myasthenic syndromes are diagnosed based on clinical examination, symptoms, specialized testing on the muscles and nerves (electrodiagnostic testing) and genetic testing. Other diagnostic tests that might be used include:

  • Electromyography (EMG) and repetitive nerve stimulation (RNS) tests – which check the health of muscles and nerves
  • Blood testing for antibodies related to muscle disease
  • Genetic testing for a gene change associated with CMS

Other testing might include :

Last updated on 05-01-20

How are congenital myasthenic syndromes inherited?

Most subtypes of CMS are inherited in an autosomal recessive manner, including the ones caused by the CHAT , COLQ , RAPSN , CHRNE , DOK7 , and GFPT1 genes. A few subtypes are inherited in an autosomal dominant manner.

All individuals inherit two copies of each gene. To have an autosomal recessive condition, a person must have a mutation in both copies of the responsible gene in each cell. People with an autosomal recessive condition inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive disorder typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, each child has a:

  • 25% (1 in 4) chance to have the disorder
  • 50% (1 in 2) chance to be an unaffected carrier like each parent
  • 25% (1 in 4) chance to be unaffected and not be a carrier

To have an autosomal dominant condition, a person must have a mutation in just one copy of the responsible gene in each cell. The mutation can be inherited from either parent. Some people are born with an autosomal dominant condition due to a new genetic mutation (de novo) and do not have a history of this condition in their family.

Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the mutation and the condition. Offspring who inherit the mutation will have the condition, although they could be more or less severely affected than their parent. Sometimes a person may have a gene mutation for an autosomal dominant condition and show few or no signs or symptoms of the condition.

Last updated on 05-01-20

What is the long-term outlook for people with congenital myasthenic syndromes?

Congenital myasthenic syndromes are rare and therefore, the long-term outcome is not well known. Symptoms may range from minor muscle weakness to severe weakness that makes it difficult to walk. The severity and change in symptoms over time is different between subtypes and can vary from person to person. In some, symptoms are brought on or made worse by fever, infections, or stress .

Last updated on 05-01-20

How many people have congenital myasthenic syndromes?

The exact number of people with congenital myasthenic syndromes is unknown. Some studies suggest that between 2-12 people per 1,000,000 may have CMS.

Last updated on 05-01-20

How might congenital myasthenic syndromes be treated?

There is no single treatment for congenital myasthenic syndromes. Treatment is based on the symptoms and may be determined by the specific subtype. Medications that have been used to treat CMS include:

  • AChE inhibitors
  • Potassium channel blockers
  • Ephedrine (used for COLQ- and DOK7-associated CMS)
  • Albuterol (used for COLQ- and DOK7-associated CMS)
  • Others

The response to medication is different from person to person. Genetic diagnosis of the specific sub-type of CMS is important because a medication that benefits one type of CMS can make another type worse.

Specialists that may be involved in the care of people with CMS include:

  • Neurologist
  • Pulmonologist
  • Physical therapist and occupational therapist
  • Speech therapist

Last updated on 05-01-20

Name: Muscular Dystrophy Association MDA 222 S Riverside Plaza Suite 1500
Chicago, IL, 60606, United States
Toll Free: 1-833-275-6321 (Helpline) Email: Url:
Name: Myasthenia Gravis Foundation of America, Inc. 355 Lexington Avenue, 15th Floor
New York, NY, 10017, United States
Toll Free: 800-541-5454 Fax : 212-297-2159 Email: Url:
Name: Myaware - Fighting Myasthenia Gravis Together myaware Derby, United Kingdom Phone: 01332 290 219 (UK) Email: Url:
Name: Myasthenic Kids UK PO Box 2087 Shoreham-by-Sea
West Sussex, BN43 5RH, United Kingdom
Phone: 07864 277959 Email: Url:
Name: National Organization for Rare Disorders NORD 55 Kenosia Avenue
Danbury, CT, 06810,
Phone: 203-744-0100 Toll Free: 1-800-999-6673 Fax : 203-263-9938 Email: Url: Si deseas hablar con alguien en espanol por favor llame al (844) 259-7178 para asistencia.
Sheih PB, Oh SJ. Congenital Myasthenic Syndromes Neurol Clin. May 2018; 36(2). 367-378. Reference Link Finsterer J. Congenital myasthenic syndromes Orphanet Jl of Rare Dis. Feb 26, 2019; 14(1). 57. Reference Link Engel AG. Genetic basis and phenotypic features of congenital myasthenic syndromes Handbk of Clin Neuro. 2018; 148. 565-589. Reference Link Wadwekar V, Nair SS, Tandon V, Kuruvilla A, Nair M. Congenital myasthenic syndrome: Ten years clinical experience from a quaternary care south-Indian hospital J Clin Neurosci. Dec 27, 2019; epub ahead of print. Reference Link Parr JR, Andrew MJ, Finnis M, Beeson D, Vincent A, Jayawant S. How common is childhood myasthenia? The UK incidence and prevalence of autoimmune and congenital myasthenia Arch Dis Child. Jun 2014; 99(6). 539-42. Reference Link

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