Congenital myasthenic syndromes

Description

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.

Frequency

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.

Causes

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

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.

Autosomal recessive inheritance. Credit: U.S. National Library of Medicine.

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.

Autosomal dominant inheritance. Credit: U.S. National Library of Medicine.

Other Names for This Condition

• CMS
• Congenital myasthenia
• Congenital myasthenic syndrome

Where this page came from

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