Congenital myasthenic syndromes

Overview

Congenital myasthenic syndromes are a group of rare hereditary conditions caused by a gene change that results in muscle weakness, which worsens with physical activity. Any muscles used for movement can be affected, including muscles that control speaking, chewing and swallowing, seeing and blinking, breathing, and walking.

There are many types of congenital myasthenic syndromes, depending on which gene is affected. The changed gene also determines many of the signs and symptoms and severity of the condition.

Congenital myasthenic syndromes are usually identified at birth or early childhood and are lifelong conditions.

There is no cure for congenital myasthenic syndromes. Medications are generally an effective treatment for muscle weakness symptoms. Which medication works depends on which gene is identified as the cause of the congenital myasthenic syndrome. Rarely, some children may have a mild form that doesn't need treatment.

Symptoms

Congenital myasthenic syndromes are typically identified at birth. But if signs and symptoms are mild, the condition may not be identified until childhood, or rarely, early adulthood.

Depending on the type of congenital myasthenic syndrome, the severity of signs and symptoms vary greatly, from minor weakness to the inability to move. Some symptoms can be life-threatening.

Common to all congenital myasthenic syndromes is muscle weakness that worsens with physical activity. Any muscles used for movement can be affected, but the most commonly affected muscles are those that control movement of the eyelids and eyes and chewing and swallowing.

During infancy and early childhood, progressive loss of essential voluntary muscle activity occurs with muscle use. Impaired muscle weakness can result in:

• Droopy eyelids and poor eye control, often with double vision.
• Difficulty chewing and swallowing.
• Weakness of facial muscles.
• Weak cry.
• Slurring or nasal speech.
• Delayed crawling and walking.
• Delayed development of wrist, hand and finger skills, such as brushing teeth or combing hair.
• Trouble supporting the head in an upright position.
• Problems breathing, such as feeling short of breath and having short pauses in breathing, sometimes worsened by infection, fever or stress.

Depending on the type of congenital myasthenic syndrome, other signs and symptoms can include:

• Skeletal deformities, such as joint, spine or foot deformities.
• Unusual facial features, such as narrow jaw or wide-set eyes.
• Hearing loss.
• Weakness, numbness and pain, usually in hands and feet.
• Seizures.
• Kidney problems.
• Cognitive impairment, rarely.

When to see a doctor

Talk to your doctor if you observe any signs listed above in your child or if you have concerns about your own signs or symptoms.

Causes

Caused by any one of more than 30 identified genes, the type of congenital myasthenic syndrome depends on which gene is affected.

Congenital myasthenic syndromes are classified by which location is affected in the neuromuscular junction ― the area that provides signals (impulses) between the nerve cells and the muscle cells to trigger movement (synapses). Disrupted signals that cause loss of muscle function can occur in different locations:

• Nerve cells where the impulse starts (presynaptic).
• Space between your nerve and muscle cells (synaptic).
• Muscle cells where the impulse is received (postsynaptic), the most common location.

Some types of congenital myasthenic syndromes are the result of congenital disorders of glycosylation. Glycosylation is a complex chemical process that plays a role in regulating communication between cells. Glycosylation defects can adversely affect the transmission of signals from nerve cells to muscles.

Congenital myasthenic syndromes are most commonly inherited in an autosomal recessive pattern. That means both parents must be carriers, but they do not typically show signs of the condition. The affected child inherits two copies of the abnormal gene — one from each parent. If children inherit only one copy, they won't develop the syndrome, but they'll be carriers and possibly pass the gene to their own children.

Rarely, congenital myasthenic syndromes can be inherited in an autosomal dominant pattern, meaning that only one parent passes on the affected gene. In some cases, the affected gene occurs randomly and is not inherited. In other cases, no gene can be identified.

Risk factors

A child is at risk of a congenital myasthenic syndrome if both parents are carriers of a gene known to cause the syndrome. The child then inherits two copies of the gene. Children who inherit only one copy of the gene from one parent typically won't develop the syndrome but will be carriers.