Congenital Myasthenic Syndromes (CMS)
Affecting only 3 out of 1 million people, CMS is a group of extremely rare, inherited disorders that cause muscle weakness and other symptoms. It is a chronic, lifelong disease that may develop later in life but is more commonly seen at birth or in early infancy. CMS is not an autoimmune condition and is caused by malfunctioning genes. In total, there are about 24 different genes that cause CMS, and they are grouped into 3 distinct categories1-4:
- Presynaptic: Affects certain nerve cells
- Postsynaptic: Affects cells in the muscles
- Synaptic: Affects the space between the nerve and muscle cells
All of these categories of CMS affect the neuromuscular junction—the place where nerve cells meet muscle cells. CMS interferes with how nerves cells communicate with muscle cells by decreasing the amount of a chemical called acetylcholine (ACh). The result is that the signal from nerve cells that tells the muscle to contract does not work the way it should.
In infants, symptoms may include weakness, tiredness, and droopy eyelids. Children and adults with CMS often have muscle weakness and/or muscles that are easily fatigued. They may have difficulty rising from a chair, climbing stairs, or walking.
Symptoms can vary from person to person, often depending on which genes are affected and the CMS category. These symptoms may include:
- Droopy eyelids
- Difficulty talking, chewing, swallowing, and holding up the head
- Feeding difficulties
- Respiratory problems
- Muscle weakness
- Easily fatigued
- Worsening weakness upon exertion
In infants, symptoms may include:
- Severe muscle weakness
- Breathing problems
- Delayed motor milestones (sitting, crawling, and walking)
Because CMS is so rare and its symptoms are similar to many other diseases, it is frequently misdiagnosed. CMS may be mistaken for various forms of myopathy, muscular dystrophy, and myasthenia gravis (MG). MG and other neuromuscular diseases may need to be ruled out before a confirmation of CMS is made.
A CMS diagnosis may be made based on several tests, such as looking at the patient’s medical history, a physical examination, the degree of muscle weakness, and other, such as the following:
- Genetic tests to identify the affected gene
- Electromyography (EMG) may be used to test the electrical activity of skeletal muscles
- Tests of the neuromuscular junction identify overactive versus underactive areas, helping identify the category of CMS
The treatment a patient receives for CMS will depend on which of the patient’s genes is defective and, therefore, responsible for the disease. Identifying the gene is so important because therapy that can help a person with one category of CMS might be harmful for a person with another category. While there is no FDA-approved treatment for CMS, promising research is ongoing.
When considering treatment options, which are limited, patients with CMS should consult with a board-certified neurologist who specializes in neuromuscular diseases. Catalyst Pharmaceuticals is working towards securing FDA approval for amifampridine phosphate for the treatment of CMS.
Catalyst is currently making amifampridine phosphate available on a compassionate-use basis while it seeks FDA approval. (Learn More About the Amifampridine Phosphate Expanded Access Program)
- Engel AG, Shen XM, Selcen D, Sine SM. Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. Lancet Neurol. 2015;14(4):420-434.
- Orpha.net. Orphanet report series. Rare disease collection. http://www.orpha.net/orphacom/cahiers/docs/GB/ Prevalence_of_rare_diseases_by_decreasing_prevalence_or_cases.pdf. Accessed December 13, 2017.
- Eymard B, Hantaï D, Estournet B. Congenital myasthenic syndromes. Handb Clin Neurol. 2013;113:1469-1480.
- Ohno K, Ohkawara B, Ito M. Recent advances in congenital myasthenic syndromes. Clin Exp Neuroimmunol. 2016;7(3):246–259.
- Garg N, Yiannikas C Hardy TA, et al. Late presentations of congential myasthenic syndromes: how many do we miss? Muscle Nerve. 2016;54(4):721-727.
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