Congenital myasthenic syndromes (CMS)

Congenital myasthenic syndromes (CMS) are a group of inherited conditions that affect neuromuscular transmission – the process of sending signals from nerves to muscles. This leads to muscle weakness that comes with activity, known as fatigable weakness. The onset of symptoms, the muscles affected, and response to treatment can vary depending on the specific genetic change.

CMS is not the same as myasthenia gravis, which is an autoimmune condition affecting neuromuscular transmission in children and adults. For information, see our myasthenia gravis page.

Symptoms of CMS usually begin at birth or in early childhood, but in some cases could begin in early adulthood. In general, the earlier the symptoms begin, the more severe they are likely to be. Some symptoms can be life-threatening.

Muscle weakness

All types of CMS cause muscle weakness that worsens with activity. This may affect specific muscle groups or be spread throughout all muscles in the body. In infants, CMS can cause delays in achieving motor milestones such as sitting, crawling, and walking. People may struggle to walk long distances, climb stairs, and may be more likely to fall.

Eyes

CMS can cause droopy eyelids (ptosis), where the muscles in one or both eyelids have weakened and droop. This can affect vision, as the eyelid begins to cover the pupil of the eyes. Weakness of the muscles around the eyeball can mean that the eye moves less, and more head movement is needed to look around. This can sometimes cause double vision (diplopia) which can have an impact on day-to-day activities – though this is rare.

Contractures and scoliosis

People with CMS may be born with, or later develop, significant stiffness in the joints (contractures). This is where the muscle tendons tighten up and limit the range of movement in the arms and legs, which can make fine motor skills (coordination of small muscles in the fingers and hands for activities like brushing your teeth) challenging.

Some people may develop scoliosis, where the spine twists and curves to the side. It’s important to regularly monitor the spine in a specialist clinic; a spinal brace may be recommended to improve posture and slow the progression of the curvature. In some cases, scoliosis surgery may be needed.

Respiratory

In some types of CMS, weak breathing muscles can cause respiratory issues from an early age, which should be regularly monitored. If respiratory issues aren’t properly managed, they can lead to respiratory crisis and become life-threatening. Weak breathing muscles can result in frequent chest infections and nocturnal hypoventilation (shallow breathing at night). Overnight breathing problems may cause daytime sleepiness, morning headaches and nausea, poor appetite, and weight loss.

Speech and swallowing

People may have difficulties with speech and swallowing because of muscle weakness. This can cause nasal speech and make it harder to pronounce words clearly.

Swallowing can be affected and make it difficult to eat and drink safely. This can lead to coughing and choking during meals and feeling like food is stuck in the throat or chest. If symptoms start at birth, babies may have a weak suck and cry, making feeding difficult.

Genetic changes

Changes in about 35 genes are currently known to cause different types of CMS, but in some cases, the genetic change is not yet identified. These genes usually make proteins that are responsible for the structure or function of the neuromuscular junction, which is the connection between a nerve and a muscle. When these genes have changes, it affects neuromuscular transmission – the process of sending signals from nerves to muscles – and can cause muscle weakness.

CMS can be classified based on where the problem happens along the signal route:

• Pre-synaptic CMS: at the nerve ending
• Synaptic CMS: in the gap between the nerve and muscle
• Post-synaptic CMS: on the muscle

Post-synaptic CMS subtypes are the most common. Changes in the CHRNE gene is the most frequent cause, followed by the RAPSN gene and DOK7 gene.

Inheritance

Most types of CMS are inherited in an autosomal recessive pattern, meaning both copies of the gene (one from each parent) must be changed for the condition to occur. In a few cases, CMS is inherited in an autosomal dominant pattern, meaning a person only needs to inherit one changed gene from either parent to develop the condition. Slow channel CMS is the most common form of this. Rarely, there may be no family history of the condition, and a gene change can happen on its own.

For more information, see our inheritance and genetics page.

A neurologist, a doctor who specialises in conditions that affect the muscles and nervous system, can carry out tests to diagnose CMS. The process usually includes a combination of physical examination, blood tests, repetitive nerve stimulation, and single fibre electromyography. Because different types of CMS can cause different symptoms and patterns of weakness, diagnosing it can be difficult. On some occasions, a muscle biopsy may also be needed. There are known genes that cause CMS, and these can be identified using a blood test.

For more information, see our diagnosis page.

Access to a healthcare team

It’s important to have access to a multi-disciplinary healthcare team. This involves different healthcare professionals working together. Usually, the lead professional will be a neurologist in a specialist neuromuscular clinic. If you do not have a neurologist or specialist doctor, speak to your GP about getting access to one.

Medication

There are medications that can help improve and maintain muscle function in people with CMS. However, some medications that benefit some types of CMS can worsen other types, so it’s important to have a genetic diagnosis before starting treatment. The most commonly used medication is pyridostigmine, followed by 3,4 diaminopyridine (3,4-DAP), salbutamol, ephedrine, and fluoxetine.

Respiratory

The level of breathing weakness can vary from mild to life-threatening, so appropriate management is crucial. Respiratory function and lung capacity should be monitored at regular checkups where possible. Overnight sleep studies are used to assess breathing while sleeping and diagnose night-time breathing problems. This is usually nocturnal hypoventilation, where low oxygen levels and high carbon dioxide levels (while sleeping) can cause symptoms of morning headaches and daytime fatigue. Nocturnal hypoventilation can be treated using non-invasive ventilation (NIV) during sleep.

Exercise and physiotherapy

It’s important to stay active and do regular gentle exercise to maintain muscle strength. It also prevents or slows the progression of joint stiffness (contractures). A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy. They can help put together a suitable exercise plan. Children may require support and encouragement from caregivers to perform physiotherapy safely and regularly. Moderate exercises like swimming and walking are highly recommended. This type of aerobic exercise helps maintain a healthy cardiovascular system and a steady weight. Sometimes, using a wheelchair can help manage fatigue. For advice for adults, see exercising with a muscle wasting condition.

Speech and swallowing

A speech and language therapist can carry out an assessment and provide support if facial and throat weakness is affecting speech or swallowing. Speech therapy can help people improve their speech clarity and communication skills. This may include exercises to strengthen the muscles needed for speech, techniques to improve articulation, or strategies to compensate for speech difficulties.

A speech and language therapist can also provide swallowing assessment and advice to address swallowing difficulties (dysphagia). A dietitian can suggest dietary changes to ensure adequate nutrition. They may suggest food supplements and high-calorie drinks. In severe cases, a feeding tube (gastrostomy) may be recommended.

Some medications can interfere with neuromuscular transmission or muscle function and worsen CMS symptoms. This can include antibiotics, muscle relaxants, heart medications, or some psychiatric drugs. It’s important that a GP or medical professional knows about a CMS diagnosis before taking a new medication. If there is any concern, speaking to a neurologist or specialist team before taking new medication is advised. A full list of medications can be found on Myaware.

Before having any surgery or treatment, it’s essential to tell the anaesthetist and surgical team of a CMS diagnosis. They should carry out a pre-operative assessment and extended post-operative monitoring to ensure safety.