OVERVIEW

What is congenital myasthenic syndrome?

Congenital myasthenic syndromes (CMS) are a group of rare neuromuscular junction disorders. The "neuromuscular junction" is where nerve fibers and muscle fibers connect, composed of structures called "synapses." Electrical signals from the brain travel through nerve fibers to the synapses, where they are converted into chemical signals. After crossing the synapse, they are transformed back into electrical signals that reach the muscle fibers, controlling limb movement. If there is a problem at the synapse, the brain's commands cannot be transmitted to the muscles, resulting in an inability to control limb movement—what is commonly referred to as "myasthenia."

Congenital myasthenic syndrome is an inherited congenital disorder. Infants or young children may exhibit mild to severe myasthenia, and the prognosis varies widely depending on the severity of the condition. In severe cases, respiratory muscle weakness may lead to death.

What are the types of congenital myasthenic syndrome?

Congenital myasthenic syndromes are classified into major categories based on the site of the defect: presynaptic, synaptic cleft, postsynaptic, and glycosylation abnormalities. They are further divided into many subtypes based on specific mutated genes. The most common type is AChR deficiency, accounting for about 50% of cases. Other subtypes include COLQ mutation, DOK7 mutation, RAPSN mutation, fast-channel syndrome, and slow-channel syndrome.

Is congenital myasthenic syndrome common?

Congenital myasthenic syndrome is a rare disease. Reported incidence rates are approximately 1.8 per million in Spain and 9.2 per million in the UK. However, certain populations, such as the Roma in southeastern Europe and the Maghreb people in North Africa, may have a higher risk of developing the condition.

SYMPTOMS

What are the manifestations of congenital myasthenic syndrome?

The most typical manifestation is muscle weakness, commonly including drooping eyelids that cannot be lifted, eye muscle paralysis preventing eye movement, vocal cord paralysis leading to loss of voice, etc. It may also present as walking difficulties or urinary incontinence. The most severe symptom is respiratory muscle weakness, which can cause fatal breathing failure in affected children.

However, clinical symptoms may vary among certain subtypes. For example, the DOK7 mutation type typically does not involve eye movement issues but often presents with limb weakness, while the RAPSN mutation type may exhibit neonatal hypotonia, joint contractures, and rarely, eye muscle paralysis.

CAUSES

Why do people get congenital myasthenic syndrome?

Congenital myasthenic syndrome is caused by genetic issues, inherited mostly as autosomal recessive traits, while the slow-channel syndrome type follows an autosomal dominant inheritance pattern.

Is congenital myasthenic syndrome hereditary?

Yes.

Is congenital myasthenic syndrome contagious?

No.

DIAGNOSIS

How to diagnose congenital myasthenic syndrome?

Diagnosis is primarily based on family history and clinical manifestations. Electromyography can assist in confirmation, while genetic testing can definitively identify the subtype.

What tests are needed if congenital myasthenic syndrome is suspected?

• Electromyography (EMG): Electrodes are placed on the muscles, and needle electrodes may also be used to assess muscle function. Needle electrodes may cause a stinging sensation, similar to an injection.
• Genetic testing: Blood is drawn to directly detect relevant gene mutations. This test is relatively expensive and time-consuming.

Which diseases are easily confused with congenital myasthenic syndrome? How to differentiate them?

Congenital myasthenic syndrome is often confused with myasthenia gravis, primary myopathy, or motor neuron diseases (e.g., ALS). Myasthenia gravis rarely occurs in children under 1 year old and lacks a family history. Primary myopathy and motor neuron diseases can be distinguished through EMG and genetic testing.

TREATMENT

Which department should be consulted for congenital myasthenic syndrome?

Neurology.

Is it necessary to seek medical treatment for congenital myasthenic syndrome?

Yes. Since the disease cannot be cured, prompt medical attention is required.

How is congenital myasthenic syndrome treated?

Currently, there is no authoritative treatment method due to the rarity of the disease and the lack of large-scale clinical data. However, based on existing reports, treatment approaches vary for different subtypes. For example, AChR deficiency, RAPSN mutation, fast-channel syndrome, and glycosylation abnormalities may be treated with acetylcholinesterase inhibitors (such as pyridostigmine). In contrast, DOK7 and COLQ mutations may worsen with pyridostigmine and could instead be managed with salbutamol or ephedrine.

Regardless of the subtype, respiratory function must be closely monitored in congenital myasthenic syndrome. If respiratory muscle weakness occurs, timely ventilatory support is essential.

Can congenital myasthenic syndrome be cured?

No. However, the condition is rarely fatal, and most affected children experience mild symptoms that do not significantly impact daily life. In very rare cases, severe respiratory muscle weakness may lead to death.

DIET & LIFESTYLE

What should patients with congenital myasthenic syndrome pay attention to in daily life?

Pay attention to respiratory function. If respiratory muscle weakness occurs, seek medical attention promptly to receive ventilatory support from a doctor.

Does congenital myasthenic syndrome affect fertility?

No. However, genetic screening should be conducted in advance to minimize the risk of the next generation inheriting the disease. Some reports also suggest that pregnancy may worsen the condition.

Can individuals with congenital myasthenic syndrome fly, engage in strenuous exercise, or travel to high-altitude areas?

If the condition is mild with no significant respiratory muscle involvement, these activities are generally permissible.

PREVENTION

Can Congenital Myasthenic Syndrome Be Prevented? How to Prevent It?

To prevent offspring from being affected, preimplantation genetic diagnosis technology can be used to avoid the next generation from inheriting the condition.