Congenital myasthenic syndromes

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Congenital myasthenic syndromes are a group of conditions that are characterized by weak muscles that tire easily (myasthenia). In people with these conditions, myasthenia typically begins shortly after birth or during early childhood. The most commonly affected muscles are the muscles in the head and neck (bulbar muscles) that control chewing and swallowing, speech, and facial expressions; the muscles that move the eyes and eyelids; and the muscles in the arms and legs. However, any of the muscles used for movement (skeletal muscles) can be affected.

In individuals with congenital myasthenic syndromes, episodes of severe weakness or breathing problems may be triggered by fevers, infection, or tiring physical activity. The severity of the myasthenia varies greatly, from minor muscle weakness to severe weakness that may require wheelchair assistance.

Babies with congenital myasthenic syndromes may have feeding difficulties. Some affected babies may also experience short pauses in breathing (apnea) that can lead to a bluish appearance of the skin or lips (cyanosis). In severe instances, a lack of movement before birth can lead to joint deformities (contractures) that cause joint stiffness (arthrogryposis) and impair movement.

Children with congenital myasthenic syndromes may have speech problems (dysarthria) or swallowing difficulties (dysphagia). The development of motor skills, such as crawling or walking, may be delayed in these children.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in more than 35 genes can cause congenital myasthenic syndromes. Variants in the CHRNE gene are responsible for about half of all cases. Variants in the COLQ and DOK7 genes are responsible for 20 to 30 percent of all cases. Variants in other genes are each responsible for a small percentage of cases.

All of the genes that are associated with congenital myasthenic syndromes provide instructions for producing proteins that are involved in the normal function of the neuromuscular junction. The neuromuscular junction is the area between nerve cells and muscle cells where signals are passed on to trigger muscle movement.

The gene variants that cause congenital myasthenic syndromes lead to changes in these proteins and disrupt the signaling between nerve cells and muscle cells. Disrupted signaling between these cells impairs the ability to move skeletal muscles. This leads to myasthenia, which affects facial muscle movements, delays the development of motor skills, and causes the other signs and symptoms of congenital myasthenic syndromes. The breathing problems seen in people with congenital myasthenic syndromes are caused by impaired movement of the muscles of the chest wall and the muscle that separates the abdomen from the chest cavity (the diaphragm).

Congenital myasthenic syndromes can be sorted into subtypes in several different ways. For example, they can be sorted by the genetic cause, the specific function of the associated gene, or the location in the cell where the associated gene functions.

Treatment of congenital myasthenic syndromes is often determined by the specific genetic cause.

Some people with congenital myasthenic syndromes do not have an identified variant in any of the genes known to be associated with these conditions. The cause of the conditions in these individuals is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Congenital myasthenia syndromes are usually inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorders. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the conditions.

In rare cases, congenital myasthenia syndromes are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorders.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The prevalence of congenital myasthenic syndromes is estimated to be 2 in 1 million individuals worldwide. In people under 18 years of age, the prevalence is estimated to be 10 in 1 million individuals.

Which doctor should you see?

The suggested department for discussing Congenital myasthenic syndromes is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Congenital myasthenic syndromes. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.