MDA leads the search for treatments and therapies for congenital myasthenic syndromes (CMS). The Association also provides comprehensive supports and expert clinical care for those living with CMS.
In this section, you’ll find up-to-date information about congenital myasthenic syndromes, as well as many helpful resources. This information has been compiled with input from researchers, physicians and people affected by the disease.
As you learn more about CMS, always remember that you’re not alone. MDA is here for you and your family, standing ready to provide help and hope. There is a place for you in the MDA CMS community.
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In addition, MDA will keep you informed through e-alerts, educational publications and speakers, seminars, videos and newsletters.
Please know that there’s a role for you in the fight against congenital myasthenic syndromes. The MDA community is strong and dedicated, with opportunities for involvement at all levels, such as:
Please know that there’s an important role for every member of the CMS community. We urge you to contact your local MDA office  to learn more.
A CMS diagnosis doesn’t mean an end to your hopes and dreams. Changes, challenges and adaptations lay ahead, but also opportunity, fulfillment, joy and hope for a future free of congenital myasthenic syndromes.
Never forget that MDA is here to help.
CMS results from genetic flaws at the neuromuscular junction — where the nerve cell meets the muscle cell.
The type of CMS depends on where the defective gene lies: (A) in the nerve cell — presynaptic CMS; (B) the muscle cell — postsynaptic CMS; or (C) the space in between — synaptic CMS.
Like myasthenia gravis (MG) , CMS is characterized by weakness and fatigue resulting from problems at the neuromuscular junction — the place where nerve and muscle cells meet (see illustration at right). But while MG is autoimmune, CMS is an inherited disease caused by defective genes.
There are many types of CMS , grouped into three main categories named for the part of the neuromuscular junction that’s affected: presynaptic (the nerve cell), postsynaptic (the muscle cell) or synaptic (the space in between).
Depending on the type, symptoms of CMS  vary from mild to severe, but generally include weakness, fatigue and ptosis (droopy eyelids). The earlier the onset of CMS, the more severe the symptoms are likely to be.
With the exception of slow-channel CMS , the inheritance pattern for the types of CMS described here is autosomal recessive. This means that it takes two copies of the defective gene — one from each parent — to cause the disease.
Slow-channel CMS is inherited in an autosomal dominant manner. This means that one copy of a defective gene is enough to cause the disease, so an affected parent has a 50 percent chance of passing the disease on to a child.
For more, see Causes/Inheritance .
As its name implies, CMS usually has a congenital (at or near birth) onset, but it can manifest in children and even in adults. Later-onset cases tend to be milder.
By identifying the genetic defects that cause CMS, MDA-funded scientists have improved the diagnosis of CMS and discovered drugs that are effective against it. They’re pursuing better drug treatments, and eyeing techniques to fix or replace the underlying genetic defects by gene therapy. For more, see Research .
This type of CMS is characterized by insufficient release of ACh (a chemical necessary for proper muscle function). It commonly manifests as CMS with episodic apnea (CMS-EA), which has its onset in infancy and causes weakness of the facial muscles and those involved in swallowing and talking, as well as episodes of apnea, a temporary cessation of breathing.
This type of postsynaptic CMS is caused by ACh receptors that are missing or don’t stay open long enough. Its symptoms vary from mild to profound. In infants, it may cause extreme weakness, feeding and respiratory problems, and delayed motor milestones (sitting, crawling and walking). Childhood and adult-onset cases often cause ptosis and fatigue, but usually don’t interfere with daily living.
This type of postsynaptic CMS is caused by ACh receptors that stay open too long. Infant-onset cases may result in extreme weakness, often leading to loss of mobility and respiratory problems in adolescence. Adult-onset cases may not be disabling.
This type is caused by deficiency of acetylcholinesterase, an enzyme that breaks down ACh. It results in extreme weakness with feeding and respiratory difficulties from birth or early childhood. Weakness also causes delayed motor milestones, and often leads to reduced mobility and scoliosis (curvature of the spine).
As its name implies, congenital myasthenic syndromes (CMS) usually have a congenital (at or near birth) onset, but the disease can manifest in children and even in adults. The different types vary in the kind and degree of symptoms, but generally speaking, the earlier the symptoms appear, the more pronounced the disease is likely to be.
Presynaptic CMS commonly appears as CMS with episodic apnea (CMS-EA). It has its onset in infancy and causes ocular weakness — weakness in muscles controlling the eyes — which can cause droopy eyelids (ptosis). It also causes bulbar weakness (named for the nerves that originate from the bulblike part of the brainstem) making it difficult to talk, chew, swallow and hold up the head. This type is also characterized by episodes of apnea, a temporary cessation of breathing.
Postsynaptic CMS (ACh receptor deficiency, fast-channel CMS) has symptoms ranging from mild to extreme. In infants, it may cause severe weakness, feeding and respiratory problems, and delayed motor milestones (sitting, crawling and walking). Childhood and adult-onset cases often cause ptosis (droopy eyelids) and fatigue, but usually don’t interfere with daily living.
Postsynaptic CMS (slow-channel CMS) causes extreme weakness in infant-onset cases, often leading to loss of mobility and respiratory problems in adolescence. Adult-onset cases may not be disabling.
Synaptic CMS can cause extreme weakness with feeding and respiratory difficulties from birth or early childhood. Weakness also causes delayed motor milestones, and often leads to reduced mobility and scoliosis (curvature of the spine).
Weakness and fatigue are common in the general population, but the degree and pattern of these symptoms — particularly ptosis (droopy eyelids) and other signs of weakness in the eye muscles — should alert a neurologist to the possibility of CMS.
The neurologist is likely to ask many questions and to conduct a physical exam to determine the extent of weakness. To look for evidence of increased weakness following exertion, the neurologist might ask patients to look up without blinking for one or two minutes, hold the arms out for as long as possible or climb up steps.
If the physical exam is consistent with myasthenia gravis (MG) , the neurologist usually orders a blood test designed to detect antibodies to the ACh receptor . A negative test for ACh receptor antibodies in the serum (blood) can help distinguish CMS from MG but doesn’t rule out seronegative MG.
If the blood tests are negative, the next step is usually electrodiagnostic testing, in which electrodes are used to measure the electrical signals in muscle. Surface electrodes (similar to those used in electrocardiograms) deliver small shocks to a nerve in the arm, leg or face, while other surface electrodes record the responses in muscle.
In addition to or in place of electrodiagnosis, the neurologist might try giving an intravenous injection of edrophonium (Tensilon), a fast-acting cholinesterase inhibitor. A temporary increase in strength after this "Tensilon test" is consistent with CMS.
A family history of myasthenic symptoms supports the CMS diagnosis but isn't necessary for CMS to occur. Genetic testing and physiological tests on biopsied muscle tissue may be needed to define some types of CMS. For more on getting a definitive genetic diagnosis, see The Genie's Out of the Bottle: Genetic testing in the 21st century .
At the normal neuromuscular junction, a nerve cell tells a muscle cell to contract by releasing the chemical acetylcholine (ACh). ACh attaches to the ACh receptor — a pore or "channel" in the surface of the muscle cell — twisting it open and allowing an inward flux of electrical current that triggers muscle contraction. These contractions enable someone to move a hand, dial the telephone, walk through a door or complete any other voluntary movement.
CMS results from flaws in genes necessary for making the ACh receptor or other components of the neuromuscular junction. The many types of CMS  are grouped into three main categories named for the part of the neuromuscular junction that’s affected: presynaptic (the nerve cell), postsynaptic (the muscle cell) or synaptic (the space in between).
Presynaptic CMS is caused by insufficient release of ACh; postsynaptic CMS (ACh receptor deficiency, fast-channel CMS) is caused by ACh receptors that are missing or don't stay open long enough; postsynaptic CMS (slow-channel CMS) is caused by ACh receptors that stay open too long; and synaptic CMS is caused by a deficiency of acetylcholinesterase, an enzyme that breaks down ACh.
With the exception of slow-channel CMS, the inheritance pattern for the types of CMS described here is autosomal recessive. This means that it takes two copies of the defective gene — one from each parent — to cause the disease.
Slow-channel CMS is inherited in an autosomal dominant manner. This means that one copy of a defective ACh receptor gene is enough to cause the disease, so an affected parent has a 50 percent chance of passing the disease on to a child. For more, see Facts about Genetics and Neuromuscular Diseases .
The cholinesterase inhibitors used to treat myasthenia gravis (MG)  are helpful in some types of congenital myasthenic syndromes (CMS) but may be harmful in others. See below for more.
It’s important to realize that since CMS isn’t an autoimmune disease, it doesn’t respond to immunosuppressant drugs or other treatments aimed at the immune system.
These drugs, also known as anticholinesterases, have been used against MG since the early 1990s and can produce relief from symptoms within minutes. The one most commonly used is pyridostigmine (Mestinon).
Cholinesterase inhibitors boost levels of ACh — a chemical necessary for proper muscle function — not only at the neuromuscular junction, but also in the autonomic nervous system (which controls involuntary bodily functions). Sometimes the drugs can cause diarrhea, abdominal cramps and/or excessive saliva. To minimize these side effects, the physician might lower the dose of cholinesterase inhibitors or prescribe atropine, which blocks the ACh receptors on nerve cells.
The types of CMS that respond to cholinesterase inhibitors include:
Types of CMS that do not respond to cholinesterase inhibitors include:
In the past, people with congenital myasthenic syndromes (CMS) were often told they had myasthenia gravis (MG)  and were subjected to years of pointless immunosuppressive therapy.
By identifying the genetic defects that cause CMS, MDA-funded scientists have improved the diagnosis of CMS and discovered drugs that are effective against it.
MDA-supported scientists are continuing to probe the genetic and molecular underpinnings of the various congenital myasthenic syndromes so that specific treatments for these can be developed or refined.
Current projects include the development of a new mouse model of a congenital myasthenic syndrome; genetic analysis of a worm with a slow-channel myasthenic syndrome; studies of how the nerve-muscle junction forms; and overall methods to improve the diagnosis, treatment and prevention of congenital myasthenic syndromes.
For more, read the Quest article Managing Myasthenia .
A clinical trial is a test in humans of an experimental medication or therapy. Clinical trials are experiments, not treatments, and participation requires careful consideration.
Although it's possible to benefit from participating in a clinical trial, it's also possible that no benefit — or even harm — may occur. Keep your MDA clinic  doctor informed about any clinical trial participation. (Note that MDA has no ability to influence who is chosen to participate in a clinical trial.)
For more about clinical trials in general, see Learn About Clinical Studies , and to learn more about trial participation in neuromuscular disease, read the Quest magazine article Being a Co-Adventurer .
For a more refined list of CMS clinical trials, visit ClinicalTrials.gov , a registry of federally and privately supported clinical trials in the United States and around the world. Select "Search for Clinical Trials," and follow the instructions to narrow down your search results.