Congenital myasthenic syndromes (CMS) are a group of genetic neuromuscular conditions that affect the communication between nerve and muscle cells (neuromuscular transmission). CMS are characterised by muscle weakness, which worsens with physical activity and mostly affects the muscles of the face, neck, throat, eyes and limbs.^1,2 There are various subtypes of CMS,³ which differ in symptoms, severity, and treatments.¹ Approximately 30 genes have been associated with CMS so far, with genetic testing necessary to differentiate between the subtypes.¹

CMS typically presents at birth or in early childhood, usually within the first decade of life.³ Symptoms range from mild to severe muscle weakness and may worsen over time or only occur periodically.¹ CMS are sometimes misdiagnosed as other myasthenic conditions, such as myasthenia gravis and Lambert-Eaton Myasthenic Syndrome, which are both autoimmune conditions and not genetic.

Synonyms: Congenital myasthenia

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:590 Congenital myasthenic syndrome

ICD-11: 8C61 Congenital myasthenic syndromes

CMS are characterised by fatiguable weakness (weakness that worsens with physical activity and may improve temporarily with rest), mainly in the skeletal muscles such as muscles of the face, neck, throat, eyes and limbs, at birth or in early childhood.^1-3

Other symptoms may present at birth, including feeding and respiratory difficulties, poor suck and cry, choking spells, noisy breathing (stridor) and drooping eyelid (ptosis).³ Some babies may have joint stiffness (contractures or arthrogryposis multiplex congenita) due to lack of movement in utero. There may also be delayed development of motor skills during childhood.³

Degeneration of muscle tissue (atrophy) is usually not observed with CMS, except for a specific CMS that is caused by defects in the GMPPB gene (GMPPB-related CMS).³

Please speak to your medical team to learn more about the symptoms and complications of a specific type of CMS.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

CMS are caused by genetic changes (variants) in specific genes that affect communication between nerve and muscle cells.  More than 30 genes have been identified to cause CMS.³ Please visit GeneReviews®: Congenital Myasthenic Syndromes (Subtypes and Genetic Causes) for more information about the different types of CMS and the associated genes.

Most CMS are inherited in an autosomal recessive manner, however some genetic variants have been associated with an autosomal dominant pattern.³ More information on the relevant inheritance patterns can be found at:

• Centre for Genetics Education: Autosomal dominant inheritance
• Centre for Genetics Education: Autosomal recessive inheritance

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of CMS may involve a combination of medical and family history, physical examination, electromyography (EMG) testing to determine a defect in neuromuscular transmission, as well as genetic testing to identify the causal gene.³ Identification of the type of CMS is said to be important to ensure treatment is suitable.²

A differential diagnosis can rule out other conditions that have similar symptoms, such as myasthenia gravis, spinal muscular atrophy, congenital muscular dystrophies, congenital myopathies, mitochondrial myopathies, congenital disorders of glycosylation, Moebius syndrome, infantile botulism, brain stem anomalies, motor neuron disease, Limb-girdle muscular dystrophy, Facioscapulohumeral muscular dystrophy, mitochondrial myopathy and chronic progressive external ophthalmoplegia and autosomal dominant progressive external ophthalmoplegia.³

Please speak to your medical team to learn more about the available diagnostic pathways for CMS.

There is currently no curative treatment or published consensus management guidelines for CMS.^2.3 Treatment is targeted at managing symptoms (symptomatic management) and involves a multidisciplinary care team. Medication may be used to manage symptoms, but the type of medication that is recommended depends on the type of CMS.³

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

Healthcare professionals involved in the treatment of CMS may include general practitioners (GP), genetic counsellors or clinical geneticists, neurologists, ophthalmologists, occupational therapists, speech pathologists, physiotherapists, and exercise physiologists.¹ The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

We are not aware of any current clinical care guidelines for CMS in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page.

GeneReviews®:Congenital Myasthenic Syndromes (Management) contains recommendations for evaluations following initial diagnosis, medical management in general and when possible, based on the genetic cause, as well as recommended surveillance for individuals with CMS.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

It may be important to consider the following when managing individuals living with RD at emergency departments/services:

• it should be noted that treatment of an individual’s CMS symptoms may depend on the type of CMS and may differ from the treatment used for myasthenia gravis (MG). It has been recommended that a neurologist be consulted prior to administering medication
• individuals with CMS  may carry a medical alert card that explains their specific condition and causal gene, as well as a list of general drugs that can exacerbate symptoms, which may provide useful information for emergency care

Information about myasthenia research in Australia can be found at:

• Myasthenia Alliance Australia: Research updates
• Myasthenia Alliance Australia: Latest research

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance and activities.

Australian Organisations:

Myasthenia Alliance Australia (MAA)
Website: https://myastheniaalliance.org.au/

Below are the organisations that make up MAA; both organisations provide support for all Australians living with myasthenia, including their families and carers, regardless of location:

Myasthenia Gravis Association of Queensland Inc.
Website: https://www.mgaq.org.au/

The Australian Myasthenic Association in NSW Inc.
Website: https://www.myasthenia.au/

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

CMS varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

Myasthenia Alliance Australia and its state organisations provide support resources relevant for individuals living with CMS:

• Myasthenia Alliance Australia: Peer Support
• Myasthenia Gravis Association of Queensland Inc.: Resources
• Australian Myasthenic Association in NSW: Patient Support

The Loop – Your Neuromuscular Resource Hub: Funding provides information on available social services that are relevant to the neuromuscular community.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on CMS or neuromuscular conditions in general can be found at:

• Genetic and Rare Diseases (GARD) Information Center: Congenital Myasthenic Syndromes
• National Organization for Rare Diseases (NORD): Congenital Myasthenic Syndromes
• The Loop – Your Neuromuscular Resource Hub
• RARE Portal: Neuromuscular conditions

• GeneReviews^®: Congenital Myasthenic Syndromes
• Orphanet: Congenital Myasthenic Syndrome
• Human Phenotype Ontology (HPO): Congenital Myasthenic Syndrome

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with Myasthenia Alliance Australia,  which represents Myasthenia Gravis Association of Queensland Inc. and The Australian Myasthenic Association in NSW.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.