Congenital myasthenic syndrome (CMS) is a group of rare, congenital (at or near birth onset) hereditary conditions characterized by muscle weakness and fatigue (myasthenia) that worsen with physical exertion. The weakness typically begins in early childhood but can appear in adolescence or adulthood as well. CMS results from a neuromuscular junction defect.
The neuromuscular junction is the area between the ends of nerve cells and muscle cells where signals are relayed to trigger or stimulate muscle movements. It comprises a presynaptic region, a synaptic space, and a postsynaptic region.
Although any of the skeletal muscles used for movement can be affected, facial muscles (including muscles that control the eyelids, muscles that move the eyes, and muscles used for chewing and swallowing) are the most commonly affected.
What are the types of congenital myasthenic syndrome?
Depending on the neuromuscular junction affected, congenital myasthenic syndrome (CMS) is grouped into three main categories:
- Presynaptic CMS:
- Characterized by the insufficient release of acetylcholine (ACh), which is a chemical necessary for proper muscle function.
- It commonly manifests as CMS with episodic apnea, which has its onset in infancy and causes weakness of the facial muscles and those involved in swallowing and talking.
- It also involves episodes of apnea (a temporary cessation of breathing).
- Postsynaptic CMS: Can be divided into fast-channel CMS and slow-channel CMS.
- Fast-channel CMS
- Caused by missing or deficient ACh receptors.
- In infants, it may cause extreme weakness, feeding and respiratory problems, and delayed motor milestones (sitting, crawling, and walking). In contrast, childhood and adult-onset cases often cause ptosis and fatigue that do not interfere with daily living.
- Slow-channel CMS
- Caused by ACh receptors that stay open for a longer time.
- Infant-onset cases may result in extreme weakness, loss of mobility, and respiratory problems in adolescence.
- Fast-channel CMS
- Synaptic CMS:
- Caused by a deficiency of acetylcholinesterase, an enzyme that breaks down ACh.
- Symptoms include extreme weakness with feeding and respiratory difficulties since birth or early childhood.
- Severe weakness may lead to delayed motor milestones, reduced mobility, and scoliosis (curvature of the spine).
What causes congenital myasthenic syndrome?
Mutations in the CHRNE gene are responsible for more than half of all congenital myasthenic syndrome (CMS) cases. However, a large number of cases are caused by mutations in the RAPSN, CHAT, COLQ, and DOK7 genes.
These genes are responsible for providing instructions necessary for producing proteins that are involved in the normal functioning of the neuromuscular junction.
Genetic mutations cause changes in proteins, disrupting signaling between the ends of nerve cells and muscle cells, which results in an impaired ability to move skeletal muscles, muscle weakness, and delayed development of motor skills.
CMS is an inherited disease caused by defective genes in an autosomal recessive pattern, which means two copies of the defective gene, one from each parent, are needed to cause the disease.
Slow-channel CMS is inherited in an autosomal dominant manner, which means that one copy of a defective gene is sufficient to cause the disease, so an affected parent has a 50 percent risk of passing the disease to a child.
What are the symptoms of congenital myasthenic syndrome?
The symptoms of the congenital myasthenic syndrome (CMS) vary from mild to severe but generally include the following:
- Weakness that worsens with exertion
- Fatigue
- Ptosis (droopy eyelids)
- Feeding difficulties or poor sucking
- Dysphagia
- Nasal regurgitation
- Dysphonia
- Poor head control
- Spinal rigidity
- A weak cry
- Nystagmus (involuntary, rapid, rhythmic eye movements)
- Delayed motor skills (crawling or walking)
In severe cases, people may experience the following:
How is congenital myasthenic syndrome diagnosed?
To diagnose congenital myasthenic syndrome (CMS), the following tests can be done:
- Medical history and physical examination
- Neurological examination
- Blood tests: To detect anti-AChR and anti-MuSK antibodies.
- Electrodiagnostic testing: To measure the electrical signals in muscles using electrodes.
- Tensilon test: A temporary increase in strength after intravenous injection of Tensilon (edrophonium), a fast-acting cholinesterase inhibitor, is consistent with CMS.
How is congenital myasthenic syndrome treated?
The following medications can be beneficial in the treatment of congenital myasthenic syndrome (CMS):
- Cholinesterase inhibitors or anticholinesterases
- The drug used is Mestinon (pyridostigmine).
- Cholinesterase inhibitors work by boosting the levels of acetylcholine (ACh), a chemical necessary for the appropriate functioning of the muscles.
- Potassium channel blockers
- 3,4-diaminopyridine may be used to increase the release of ACh and prolong the presynaptic action potential.
- Adrenergic agonist
- This treatment shows positive effects in different subtypes of CMS.
- Beta-2-agonist
- It is effective in several CMS subtypes, particularly in patients with endplate acetylcholinesterase deficiency and those with DOK7 pathogenic variants.
Congenital Myasthenic Syndromes (CMS) Muscular Dystrophy Association https://www.mda.org/disease/congenital-myasthenic-syndromes
Congenital myasthenic syndrome Medline Plus https://medlineplus.gov/genetics/condition/congenital-myasthenic-syndrome/#synonyms
Congenital Myasthenic Syndromes NORD https://rarediseases.org/rare-diseases/congenital-myasthenic-syndromes/
Congenital myasthenic syndromes GARD https://rarediseases.info.nih.gov/diseases/11902/congenital-myasthenic-syndromes
Top What Is Congenital Myasthenic Syndrome Related Articles
Fatigue Causes Slides
Always feeling tired? Learn more about the causes of fatigue. Get tips to relieve symptoms of fatigue. Feel less tired and start living awake and refreshed.Chronic Fatigue Quiz
Exhausted all the time? Maybe it's not all in the mind. Take the Chronic Fatigue Syndrome (CFS) Quiz to learn more about tricky condition.Does Being Cold Make Your Muscles Ache?
Cold weather can tighten the muscles and joints, leading to muscle aches and pain.Fatigue and Exhaustion
Fatigue can be described in various ways. Sometimes fatigue is described as feeling a lack of energy and motivation (both mental and physical). The causes of fatigue are generally related to a variety of conditions or diseases, for example, anemia, mono, medications, sleep problems, cancer, anxiety, heart disease, and drug abuse.Treatment of fatigue is generally directed toward the condition or disease that is causing the fatigue.
Genetic Diseases
The definition of a genetic disease is a disorder or condition caused by abnormalities in a person's genome. Some types of genetic inheritance include single inheritance, including cystic fibrosis, sickle cell anemia, Marfan syndrome, and hemochromatosis. Other types of genetic diseases include multifactorial inheritance. Still other types of genetic diseases include chromosome abnormalities (for example, Turner syndrome, and Klinefelter syndrome), and mitochondrial inheritance (for example, epilepsy and dementia).11 Surprising Things Your Genes Say About You
Explore what role DNA plays in your health, love life, and more in this WebMD slideshow.How Can I Relieve Muscle Soreness?
Here are 11 different ways to relieve muscle soreness at home following an intense workout or rigorous physical activity.Muscle Cramps
Muscle cramps are involuntarily and forcibly contracted muscles that do not relax. Extremely common, any muscles that have voluntary control, including some organs, are subject to cramp. Since there is such variety in the types of muscle cramps that can occur, many causes and preventative medications are known. Stretching is the most common way to stop or prevent most muscle cramps.Muscle Cramps (Charley Horse) and Muscle Spasms
What are the differences between muscle spasms and cramps? Learn about the causes of muscle spasms and cramps (charley horse) in the calf, leg, and more.Muscle Pain (Myofascial Pain Syndrome)
Muscle pain (myofascial pain syndrome) is muscle pain in the body's soft tissues due to injury or strain. Symptoms include muscle pain with tender points and fatigue. Treatment usually involves physical therapy, massage therapy, or trigger point injection.Muscle Spasms
Muscle spasms are involuntary muscle contractions that come on suddenly and are usually quite painful. Dehydration, doing strenuous exercise in a hot environment, prolonged muscle use, and certain diseases of the nervous system may cause muscle spasms. Symptoms and signs of a muscle spasm include an acute onset of pain and a possible bulge seen or felt beneath the skin where the muscle is located. Gently stretching the muscle usually resolves a muscle spasm.Pain Management: Signs Your Muscle Pain Is Something Else
Could your achy muscles be a sign of more than a tough workout? Learn when a twinge might warrant a visit to the doctor's office.What Are the Three Grades of Muscle Strain?
Depending on the severity of damage, muscle strains are classified into three grades. Learn about symptoms, causes, and treatment.What Causes Weakness in the Knee?
Knee weakness can be caused by a wide range of factors, from injuries to illnesses. The most common cause is damage to the ligaments.When Should I Worry About Muscle Twitching?
What is muscle twitching, and how do you recognize it? Muscle twitching is a common issue that affects many people. Learn the signs of muscle twitching, what causes it, when to see a doctor, and how to treat it. Sore muscles after exercise is normal and a sign your muscles are repairing themselves. Extreme soreness, however, may be a sign that you've overdone it.