According to abbreviationfinder, CMS stands for Congenital myasthenic syndrome. The congenital myasthenic syndrome is genetic and belongs to the myasthenic syndromes. It is characterized by a disruption in signal transmission between nerve and muscle cells. The symptoms of this group of diseases vary greatly in severity. A particular phenotype of limb-girdle myasthenia is observed in some patients.
What is Congenital Myasthenic Syndrome?
The diagnosis of the congenital myasthenic syndrome is based on anamnesis, serological examinations, genetic analyzes and diagnosis by the administration of cholinesterase inhibitors.
The congenital myasthenic syndrome is a collective term for various genetic diseases that become noticeable through a disruption in signal transmission between nerve and muscle cells. This is a group of congenital myasthenias (muscle weaknesses) that lead to increased fatigability of the skeletal muscles, mainly under physical stress.
The word “congenital” means “innate” and already indicates a genetic cause. Overall, the congenital myasthenic syndrome belongs to the myasthenic syndromes along with myasthenia gravis, neonatal myasthenia and the Lambert-Eaton-Rooke syndrome. However, while the congenital myasthenic syndrome is genetic, all other myasthenic syndromes are caused by autoimmune processes.
The diseases of the congenital myasthenic syndrome are inconsistent. The only common feature is the disruption of signal transmission from the nervous system to the skeletal muscles, resulting in muscle weakness. Around 2,000 to 3,000 confirmed cases are known worldwide. However, it is assumed that twice the number of people suffer from this syndrome. There is said to be a prevalence of two in a million.
Congenital myasthenic syndrome can be caused by various mutations of genes involved in excitation transmission processes. This involves at least 14 genes. Both autosomal recessive and autosomal dominant inheritance have been observed. The signal transmission from the nerve to the muscle cells takes place via the neurotransmitter acetylcholine at the motor end plate.
The motor endplate represents a chemical synapse between nerve and muscle fibers. In order to transmit the excitation, acetylcholine first enters this synapse and binds to acetylcholine receptors located on the surface of the muscle cells. This binding causes the ion channels of the muscle fibers to open, with the consequent depolarization of the membrane potential due to the influx of calcium and sodium ions into the interior of the cell.
The change in potential triggers a muscle contraction. From the synaptic cleft, acetylcholine is then hydrolyzed to acetate and choline by the enzyme acetylcholinesterase. As the acetate diffuses out of the cleft, choline is taken up again by the presynaptic cell and used again to form acetylcholine.
The signal transmission process can be disrupted by the lack of or defective formation of acetylcholine receptors and by problems with the transport of acetylcholine. A transmission of excitation does not come about or only insufficiently. The acetylcholine receptors or the presynaptic calcium channels are destroyed by autoimmune processes in the acquired forms of myasthenic syndrome such as myasthenia gravis or Lambert-Eaton-Rooke syndrome.
In congenital myasthenic syndrome, however, genetically determined errors in the formation of acetylcholine receptors or choline acetyltransferase lead to the signal transmission disorders.
Symptoms, Ailments & Signs
The symptoms of congenital myasthenic syndrome are very different. Even with an identical gene mutation, there can be significant deviations in the expression of the symptoms. As a rule, the symptoms begin before birth or in the first months of life. In rare cases, however, they first appear in adolescence or even in adulthood.
The spectrum of complaints ranges from almost symptom-free to the development of the most severe symptoms. The main symptom present in all patients is the rapid fatigability of the skeletal muscles. This primarily affects the eyelids (ptosis), the eye muscles, the facial muscles, the throat or the respiratory muscles. Paralysis of the trunk and extremities is also often present.
The eyelids droop in ptosis. Some patients squint or see double vision. The face may appear expressionless. Other symptoms include difficulty swallowing and difficulty drinking. Some patients also have a weak voice. Sometimes respiratory paralysis occurs. As a rule, however, not all muscles are affected by the muscle weakness in the individual patient.
It is typical that the symptoms mainly appear after physical exertion or in the evening. In some patients, infections or even excitement can lead to a sudden worsening of the symptoms. In some cases, the disease progresses continuously over months or years. Although most of those affected can walk, there are also patients who can only get around in a wheelchair.
Diagnosis & course of disease
The diagnosis of the congenital myasthenic syndrome is based on anamnesis, serological examinations, genetic analyzes and diagnosis by the administration of cholinesterase inhibitors. Certain gene mutations can be ruled out by the administration of cholinesterase inhibitors. The differential diagnostic exclusion of autoimmune diseases is possible with the serological tests.
In most cases, the symptoms of this syndrome appear immediately after birth, so that diagnosis and treatment can be initiated at an early stage. Those affected suffer from a greatly reduced resilience and appear very tired and exhausted. As a rule, there is also paralysis of the muscles and the person concerned is unable to carry out certain activities or sports.
There are also problems with the eyes, which can lead to visual problems, double vision or what is known as blurred vision. It is not uncommon for patients to suffer from poor drinking, which can result in dehydration. Respiratory paralysis also occurs, which negatively affects the everyday life of those affected. However, the mental and motor development of the patient proceeds without any particular complaints or complications.
In most cases, the symptoms only appear in the evening or after strenuous activity. A causal treatment of this syndrome is not possible. However, the symptoms can be reduced with the help of medication or various therapies, making everyday life easier for the patient. Life expectancy is usually not reduced.
When should you go to the doctor?
Parents who notice their child tiring easily, signs of persistent exhaustion or other unusual symptoms should consult the pediatrician . Other warning signs that always require clarification are unusual eye movements such as squinting or double vision or an expressionless face. Poor drinking, disorders of the respiratory muscles and muscle weakness are also among the symptoms of the congenital myasthenic syndrome. If these and other symptoms occur and affect the well-being of the child, a doctor must be consulted.
Even non-specific changes in the child’s behavior are best clarified quickly. Parents of affected children must consult the doctor closely during treatment and, if necessary, consult a therapist. If the prescribed medication causes side effects and interactions, the doctor should be informed. In addition to the family doctor, an internist or a specialist clinic for genetic diseases can be consulted in the case of congenital myasthenia. The individual symptoms must be treated by different specialists (e.g. ophthalmologists and orthopaedists).
Treatment & Therapy
Treatment depends on the specific genetic cause. Due to the genetic condition, however, only symptomatic therapy is possible. In some cases, good results can be achieved through the use of medication. These include cholinesterase inhibitors (pyridostigmine), ephedrine, quinidine or salbutamol.
Unfortunately, in many cases, the symptoms improve only partially or not at all during drug treatment. Furthermore, measures such as physiotherapy, ventilation, speech therapy and the provision of various aids are often required. A prognosis of the development of the disease can never be given because the courses are individual.
Outlook & Forecast
The congenital myasthenic syndrome turns out to be a mutation that can produce various clinical pictures. Doctors speak of a heterogeneous group of treatable diseases that can be inherited in either an autosomal recessive or autosomal dominant manner. They are characterized by disturbances in neuromuscular transmission.
So far, only a maximum of 3,000 cases of congenital myasthenic syndrome are known worldwide. This makes it one of the rare diseases for which there are only limited treatment options. The reason for this lies, among other things, in more than 20 different genes that can be mutated. It is known so far that the mutated genes are responsible for the disease-causing lack of acetylcholine receptors. As a result, the neuromuscular signals are insufficiently transmitted to the muscles and nerves.
Since the symptoms of genetic muscle fatigue appear early and worsen with age, drug treatment must start as early as possible. The prognosis is not uniform in congenital myasthenic syndrome. The effects of the medication administered vary. The cause of this may be the type of mutation.
In addition to the stress-related muscle problems in the legs and arms, the person affected can also be burdened by breathing problems or facial restrictions. He may have difficulty swallowing and drinking, delayed motor development, or other side effects of congenital myasthenic syndrome.
If there is a family history of congenital myasthenic syndrome, human genetic counseling and examinations should be carried out if children are desired in order to be able to assess the risk for the offspring. However, a recommendation for prevention cannot be given.
Since this syndrome is a genetic disease, it usually cannot be fully treated. Therefore, the patient should consult a doctor as soon as the first signs and symptoms of the disease appear in order to prevent the symptoms from getting worse, since self-healing cannot occur in this case. If the patient wishes to have children, genetic counseling and testing can be useful to prevent the disease from recurring in the children.
Early diagnosis usually has a very positive effect on the further course of the disease. The syndrome is treated by taking various drugs. It is always important to ensure that the dosage is correct and that it is taken regularly in order to limit the symptoms.
If anything is unclear or if there are side effects, a doctor should be contacted first. Physiotherapy measures can also have a positive effect on the course of the disease, and many of the exercises from such therapy can be carried out at home. The further course of the disease depends very much on the time of diagnosis, so that a general prediction cannot be made.
You can do that yourself
Patients with the congenital myasthenic syndrome suffer to varying degrees from their relatively weak skeletal muscles. This results in the typical symptoms, some of which can be alleviated by targeted self-help measures. The weakened eye muscles are often accompanied by various visual problems that need to be treated by an ophthalmologist and optician. The patient follows the doctor’s instructions, wears prescribed glasses and, if necessary, carries out exercises to strengthen the eye muscles.
Physiotherapeutic treatment of the patient also helps for those complaints that affect weakened muscles outside of the face. Those affected learn physiotherapy tailored to their symptoms, some of which can also be carried out at home. This results in considerable opportunities for the patient to help themselves, since they can noticeably strengthen their muscles through targeted training. In general, the patient only practices sports that the doctor expressly allows. The same applies to the intensity and scope of sporting activities.
If the person concerned also suffers from a weak voice, speech therapy treatment is an option. Their success also depends on the cooperation and personal commitment of the patient with the congenital myasthenic syndrome.