What is congenital myasthenic syndrome?
Congenital myasthenic syndrome (CMS) refers to a group of inherited conditions that usually develop at birth or in early childhood. These conditions cause muscle weakness that gets worse with physical activity. CMS is caused by problems at the neuromuscular junction—the place where a nerve meets the muscle cells to send signals that start movement.
Muscle weakness typically begins in infancy but may appear in adolescence or adulthood. CMS most commonly affects muscles in the face—including those that control eye and eyelid movement, chewing, and swallowing. But the condition can affect any muscle that moves the body. Other symptoms may include:
- Feeding difficulties
- Delay in motor skills, such as crawling or walking
- Skeletal abnormalities, such as spine or foot deformities
How severe the condition is and how much it affects daily life depends on the cause of CMS. Some people with CMS experience minor weakness, while others are unable to walk. Some people experience breathing problems like apnea (short pauses in breathing).
Causes of CMS
Variations (also called mutations) cause CMS. These variations happen in the genes that provide instructions for producing proteins involved in maintaining the normal structure and function of the neuromuscular junction. As a result, the proteins don’t function properly, disrupting the communication signals that pass between nerve and muscle cells. Changes in these signals result in muscle weakness and other symptoms of CMS.
Variations in the CHRNE, RAPSN, CHAT, COLQ, PLEC, SCN4A, and DOK7 genes cause many cases of CMS. Researchers have identified over 30 gene variations that cause CMS. But in some people with the condition, doctors can’t find any variations in the currently identified CMS-associated genes.
Gene variations that cause CMS can be grouped by which part of the neuromuscular junction they affect:
- Presynaptic: includes types of CMS that affect the nerve cell, where movement signals begin
- Synaptic: includes types of CMS that affect proteins in the space between the nerve and muscle cells, called the synapse
- Postsynaptic: the most common category of CMS and includes types of CMS that affect the muscle cell, which receives movement signals
In some cases, gene variations impact more than one part of the neuromuscular junction.
Who is more likely to get congenital myasthenic syndrome?
CMS is an inherited condition, meaning the mutated genes are passed down from one or both parents. In most cases, the inheritance is autosomal recessive, which means two copies of a defective gene—one from each parent—are needed to cause CMS. In rare cases, the inheritance is autosomal dominant, meaning only one copy of a defective gene can lead to CMS.
Genetic testing can help parents determine if they are carriers of a gene that causes CMS. A genetic counselor can provide information about the test and what the results could mean.
How is congenital myasthenic syndrome diagnosed and treated?
Diagnosing CMS
To diagnose CMS, a doctor will conduct a physical exam along with a neurological exam and review a person’s symptoms and medical history.
The doctor may order additional tests such as blood tests, a nerve conduction study, and electromyography (EMG) to rule out conditions with symptoms similar to CMS.
Genetic testing can help identify the specific genetic variation responsible for CMS. Knowing which gene is affected can help determine the best treatments.
Learn more about neurological diagnostic tests and procedures.
Treating CMS
There’s no cure for CMS, but medicines to help maintain or improve muscle function can help people with the condition manage symptoms. These medicines can help boost the signaling between nerves and muscles to help maintain muscle function. Selecting the appropriate medicine can depend on the specific genetic variation.
Supportive treatment such as physical, speech, and occupational therapy can help people with CMS maintain function. Assistive devices like wheelchairs, walkers, and hand and arm supports can help some people move around safely and prevent injury.
For people with apnea, supportive breathing devices such as an apnea monitor may help. Additional nutrition and tube feeding, which delivers nutrition directly into the stomach or small intestine, can help with chewing and swallowing problems. If the person has severe spine or foot deformities, they may need surgery.
What are the latest updates on congenital myasthenic syndrome?
NINDS, a part of the National Institutes of Health (NIH), is the leading federal funder of research on the brain and nervous system. NINDS conducts and supports new and innovative research to better understand, diagnose, and treat conditions such as CMS.
NINDS scientists are conducting a natural history study to learn how CMS affects the body and causes changes over time. Natural history studies collect information about a health condition to understand how it develops and to improve diagnosis and treatment options. In this NINDS study, researchers will also assess outcome measures that may be used in future clinical trials. Outcome measures are specific measurements or observations collected during a study that help scientists learn about the impact of a potential drug, device, or procedure.
Researchers funded by NINDS are developing new gene therapy products to treat specific forms of CMS. The scientists hope these products will decrease the need for medications to treat the conditions, instead creating a one-time, non-drug treatment which would be administered through a single intravenous (IV) injection. This research will reveal important information about how delivering therapeutic genes can restore essential signaling at the neuromuscular junction and promote normal physical functioning.
For more information on research about CMS, check NIH RePORTER, a searchable database of current and past research projects funded by NIH and other federal agencies. RePORTER also includes links to publications and resources from these projects.
For research articles and summaries on CMS, search PubMed, which contains citations from medical journals and other sites.
How can I or my loved one help improve care for people with congenital myasthenic syndrome?
Clinical trials increase our understanding of CMS and related disorders with the goal of improving how doctors treat them. Consider participating in a clinical trial so clinicians and scientists can learn more about CMS. Clinical research with human participants helps researchers learn more about a disorder and perhaps find better ways to detect, treat, or prevent disease safely.
All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities. This helps make sure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.
For information about participating in clinical research, visit the NINDS Clinical Trials site and NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with CMS at Clinicaltrials.gov, a searchable database of current and past clinical studies and research results.
Where can I find more information about congenital myasthenic syndrome?
Information may be available from the following sources: