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Disease Profile

Cramp-fasciculation syndrome

Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.


US Estimated

Europe Estimated

Age of onset





Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.


Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.


dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.


Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable



Cramp-fasciculation syndrome (CFS) is a rare condition of the muscles characterized by persistent muscle cramping and twitching (fasciculations) in otherwise healthy individuals. This can lead to muscle discomfort, pain, or tiredness. Muscles in the leg are most commonly affected, although this condition may involve several parts of the body. Symptoms are thought to be due to over-activity of the associated nerves. In most cases, CFS occurs sporadically in people with no family history of the condition. There is limited information about the treatment of CFS, but certain medications have been reported as beneficial in individual cases.[1][2][3]


Cramp-fasciculation syndrome (CFS) is primarily associated with spontaneous, painful muscle cramps and muscle twitches (fasciculations), in the absence of an associated underlying diagnosis. Muscles in the legs (thighs and calves) are most commonly affected, although other muscles (such as muscles in the arm or chest) can also be involved. Other signs and symptoms may include burning or prickling sensations (paresthesias), muscle stiffness, over-responsive reflexes (hyperreflexia), anxiety, and fatigue.[4][1] Symptoms are often triggered by physical activity and may be relieved by stretching exercises and/or massage. The severity of the condition varies significantly from person to person. In severe cases, CFS can interfere with daily activities and quality of life.[1]


Cramp-fasciculation syndrome (CFS) may have multiple underlying causes.[2] In general, it is thought to be related to abnormal excitability (overactivity) of peripheral neurons.[2] However, in many people with CFS, the cause cannot be found (idiopathic CFS).[2]

The following have been reported to be associated with CFS:[2][3]

Some familial cases of CFS have been reported.[5] To our knowledge, no genes have been found responsible for familial cases of isolated CFS (occurring without an associated disorder). Recently, a variant in a gene called TRPA1 was suggested to be responsible for autosomal dominant, carbamazepine-responsive CFS in a father and son. However, they were thought to have CFS as part of a more generalized hypersensitivity-hyperexcitability disorder that was causing various additional symptoms.[5] More research involving a larger number of people with CFS is needed to identify possible genetic causes of familial and/or isolated CFS.


A diagnosis of cramp-fasciculation syndrome is generally based on the presence of characteristic symptoms, in otherwise healthy individuals. A history of frequent muscle cramps, twitching, and pain (often worsened by exercise) without muscle weakness or wasting is suggestive of the condition. Some of these symptoms may be more obvious when a person is at rest (i.e. muscle twitching). It is important to rule out other conditions that may cause similar features.[3]

Electromyography (EMG) or repetitive nerve stimulation studies may also be done to assess the health of muscles and the nerves that control them. In repetitive nerve stimulation studies, muscle responses are recorded when the nerves are repetitively stimulated by small pulses of electricity.[3][6]


There is limited information in the medical literature about the treatment of cramp-fasciculation syndrome (CFS). Much of what is available describes individual cases. Some people with CFS improve without treatment. Treatment with carbamazepine, gabapentin, lamotrigine, or pregabalin (medications that reduce the hyper-excitability of nerves) was described as helpful in improving symptoms in individual cases. Immunosuppressive therapy (e.g., prednisone) has been used to treat cases of CFS that did not respond to other treatments.[3] 

Decisions regarding treatment should be carefully considered and discussed with a knowledgeable healthcare provider.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • PubMed is a searchable database of medical literature and lists journal articles that discuss Cramp-fasciculation syndrome. Click on the link to view a sample search on this topic.


  1. Tahmoush AJ, Alonso RJ, Tahmoush GP, Heiman-Patterson TD. Cramp-fasciculation syndrome: a treatable hyperexcitable peripheral nerve disorder. Neurology. July 1991; 41(7):1021-1024. https://www.ncbi.nlm.nih.gov/pubmed/1648679.
  2. Shimatani Y, Nodera H, Shibuta Y, Miyazaki Y, Misawa S, Kuwabara S, Kaji R. Abnormal gating of axonal slow potassium current in cramp-fasciculation syndrome. Clin Neurophysiol. June 2015; 126(6):1246-1254. https://www.ncbi.nlm.nih.gov/pubmed/25304174.
  3. Liewluck T, Klein CJ, Jones LK Jr. Cramp-fasciculation syndrome in patients with and without neural autoantibodies. Muscle Nerve. March 2014; 49(3):351-356. https://www.ncbi.nlm.nih.gov/pubmed/23836298.
  4. Nirenberg MJ, Chaouni R, Biller TM, Gilbert RM, Paisán-Ruiz C. A novel TRPA1 variant is associated with carbamazepine-responsive cramp-fasciculation syndrome. Clin Genet. January, 2018; 93(1):164-168. https://www.ncbi.nlm.nih.gov/pubmed/28436534.
  5. Nirenberg MJ, Chaouni R, Biller TM, Gilbert RM, Paisán-Ruiz C. A novel TRPA1 variant is associated with carbamazepine-responsive cramp-fasciculation syndrome. Clin Genet. April 24, 2017; [Epub ahead of print]:https://www.ncbi.nlm.nih.gov/pubmed/28436534.
  6. Harrison TB, Benatar M.. Accuracy of repetitive nerve stimulation for diagnosis of the cramp-fasciculation syndrome. Muscle Nerve. June 2007; 35(6):776-780. https://www.ncbi.nlm.nih.gov/pubmed/17405138.
  7. Jansen PH, van Dijck JA, Verbeek AL, Durian FW, Joosten EM.. Estimation of the frequency of the muscular pain-fasciculation syndrome and the muscular cramp-fasciculation syndrome in the adult population. Eur Arch Psychiatry Clin Neurosci. 1991; 241(2):102-4. Accessed 3/18/2015.

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