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Disease Profile

Congenital myasthenic syndromes

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

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ICD-10

G70.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

CMS; Congenital Myasthenia; Congenital myasthenic syndrome

Summary

Congenital myasthenic syndromes (CMS) are a group of genetic conditions that all include muscle weakness that gets worse with physical activity. [1][2][3][4] There are many subtypes of CMS with different symptoms, severity, and treatments. Most people with CMS develop symptoms in infancy or by early childhood, but the age at which symptoms begin can vary. Symptoms range from mild to severe muscle weakness and may get worse over time or only occur periodically.[1][3] The muscles of the face, neck, throat, eyes and limbs are most affected.[3] There are at least 32 genes associated with CMS. Most are inherited in an autosomal recessive pattern.[3] Genetic testing is necessary to tell the difference between subtypes.[2] Treatment is based on managing the symptoms, and may differ depending on the subtype. The long-term outlook is not well understood and differs greatly from person to person.[3]

Symptoms

The symptoms of the congenital myasthenic syndromes (CMS) vary by the age at which symptoms begin, type of muscle weakness and severity.[2][3][4] All subtypes involve muscle fatigue and weakness that usually begins at an early age. The most common symptoms of CMS include:

  • Muscle weakness that is brought on by activity or exercise
  • Eyelid drooping which can come and go
  • Facial and throat muscle weakness
  • Delay of motor development

Many subtypes of CMS have specific symptoms that help identify them. For example, muscle weakness in the limbs and torso is most often seen in the COLQ, DOK7, and GFPT1 subtypes, and difficulty breathing is seen most often in the CHRNE and CHAT subtypes.[3][4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Fatigable weakness
0003473
Frontalis muscle weakness
Weakness of forehead muscle
0004661
Intermittent episodes of respiratory insufficiency due to muscle weakness
0004889
Neck muscle weakness
Floppy neck
0000467
Poor suck
Poor sucking
0002033
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Ptosis
Drooping upper eyelid
0000508
Sudden episodic apnea
0002882
30%-79% of people have these symptoms
Apneic episodes precipitated by illness, fatigue, stress
0002872
Arthrogryposis multiplex congenita
0002804
Ataxia
0001251
Bulbar palsy
0001283
Central sleep apnea
0010536
Choking episodes
0030842
Cyanosis
Blue discoloration of the skin
0000961
Decreased fetal movement
Less than 10 fetal movements in 12 hours
0001558
Difficulty walking
Difficulty in walking
0002355
Easy fatigability
0003388
EMG: impaired neuromuscular transmission
0100285
Episodic respiratory distress
Episodic difficulty breathing
0004885
Generalized muscle weakness
0003324
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Muscle fiber atrophy
Muscle fiber degeneration
0100295
Nasal regurgitation
0011469
Nasal speech
Nasal voice
0001611
Ophthalmoplegia
Eye muscle paralysis
0000602
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Spinal deformities
0008443
5%-29% of people have these symptoms
Areflexia
Absent tendon reflexes
0001284
Central hypotonia
0011398
Distal amyotrophy
Distal muscle wasting
0003693
Distal lower limb muscle weakness
0009053
Dysphonia
Inability to produce voice sounds
0001618
EMG: myopathic abnormalities
0003458
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Kyphoscoliosis
0002751
Limb-girdle muscle weakness
0003325
Long face
Elongation of face
Increased height of face
Increased length of face
Vertical elongation of face
Vertical enlargement of face
Vertical overgrowth of face

[ more ]

0000276
Motor delay
0001270
Narrow jaw
Narrow lower face
Narrow lower jaw

[ more ]

0012801
Pes cavus
High-arched foot
0001761
Poor head control
0002421
Seizure
0001250
Spinal rigidity
Reduced spine movement
0003306
Stridor
0010307
Toe walking
Toe-walking
0040083
Waddling gait
'Waddling' gait
Waddling walk

[ more ]

0002515
Weak cry
0001612
1%-4% of people have these symptoms
Congenital hip dislocation
Dislocated hip since birth
0001374
Diplopia
Double vision
0000651
EEG with polyspike wave complexes
0002392
Esotropia
Inward turning cross eyed
0000565
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness

[ more ]

0001388
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Microretrognathia
Small retruded chin
0000308
Motor polyneuropathy
0007178
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Obstructive sleep apnea

Cause

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.[3]

Diagnosis

Congenital myasthenic syndromes are diagnosed based on clinical examination, symptoms, specialized testing on the muscles and nerves (electrodiagnostic testing) and genetic testing.[1][2][3] 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 [3]:

Treatment

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:[1][3]

  • AChE inhibitors
  • Potassium channel blockers
  • Ephedrine (used for COLQand DOK7-associated CMS)
  • Albuterol (used for COLQand 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.[3]

Specialists that may be involved in the care of people with CMS include:[1][3]

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

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Congenital myasthenic syndromes. This website is maintained by the National Library of Medicine.
      • Muscular Dystrophy Association has information and resources about Congenital myasthenic syndromes. Please click on the link to access this resource.

      In-Depth Information

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Congenital myasthenic syndromes in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Congenital myasthenic syndromes. Click on the link to view a sample search on this topic.

        References

        1. Sheih PB, Oh SJ. Congenital Myasthenic Syndromes. Neurol Clin. May 2018; 36(2):367-378. https://www.ncbi.nlm.nih.gov/29655455.
        2. Engel AG. Genetic basis and phenotypic features of congenital myasthenic syndromes. Handbk of Clin Neuro. 2018; 148:565-589. https://ncbi.nlm.nih.gov/pubmed/29478601.
        3. Finsterer J. Congenital myasthenic syndromes. Orphanet Jl of Rare Dis. Feb 26, 2019; 14(1):57. https://ncbi.nlm.nih.gov/pubmed/30808424.
        4. 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:https://ncbi.nlm.nih.gov/pubmed/31889643.
        5. 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. https://ncbi.nlm.nih.gov/pubmed/24500997.

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