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Disease Profile

Isaacs’ 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.

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset

All ages





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


Other names (AKA)

Neuromyotonia; Isaac's-Merten's syndrome; Continuous muscle fiber activity syndrome;


Nervous System Diseases


Isaacs' syndrome is a rare neuromuscular disorder that is characterized by progressive muscle stiffness; continuously contracting or twitching muscles (myokymia); and diminished reflexes. Signs and symptoms generally develop between ages 15 and 60, with most people experiencing symptoms before age 40. Although the exact underlying cause is unknown, there appear to be hereditary and acquired (noninherited) forms of the condition. Treatment is based on the signs and symptoms present in each person.[1][2][3]


The signs and symptoms of Isaacs' syndrome generally develop between ages 15 and 60, with most people showing symptoms before age 40. Although the symptoms can vary, affected people may experience:[1][2][3][4]

  • Progressive stiffness, cramping and weakness
  • Muscle twitching with a rippling appearance (myokymia)
  • Delayed muscle relaxation
  • Diminished reflexes
  • Muscle atrophy
  • Ataxia (difficulty coordinating voluntary movements)
  • Increased sweating

These symptoms generally persist throughout the day, even during sleep or when under general anesthesia. Speech and breathing may also be affected if the muscles of the throat are involved. Smooth muscles and cardiac (heart) muscles typically are spared.[1][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
30%-79% of people have these symptoms
Calf muscle hypertrophy
Increased size of calf muscles
EEG abnormality
EMG: myokymic discharges
Muscle twitch
Excessive sweating
Increased sweating
Profuse sweating
Sweating profusely
Sweating, increased

[ more ]

Muscle fibrillation
Muscle spasm
Muscle stiffness
Weight loss
5%-29% of people have these symptoms
Distal sensory impairment
Decreased sensation in extremities
1%-4% of people have these symptoms
Muscle weakness
Muscular weakness


The exact cause of Isaacs' syndrome is poorly understood. There appear to be hereditary and acquired (noninherited) forms of the condition. The acquired forms are often associated with malignancies, peripheral neuropathies, and a variety of autoimmune disorders of the nervous system.[1][2]


A diagnosis of Isaacs' syndrome is often suspected based on the presence of characteristic signs and symptoms. Additional testing can then be ordered to confirm the diagnosis, evaluate for associated conditions (i.e. malignancies and autoimmune disorders) and rule out other disorders that may cause similar features. This testing may included:[3]

  • Specialized laboratory studies on blood and/or urine
  • Imaging studies such as a CT scan or MRI scan
  • Electromyography which checks the health of the muscles and the nerves that control them.


The treatment of Isaacs' syndrome is based on the signs and symptoms present in each person. For example, anticonvulsant medications such as phenytoin and carbamazepine may be prescribed to relieve stiffness, muscle spasms, and pain. Plasma exchange may provide short-term relief for people with some forms of acquired Isaacs' syndrome. Plasma exchange is a method by which whole blood is removed from the body and processed so that the red and white blood cells are separated from the plasma (liquid portion of the blood). The blood cells are then returned to the patient without the plasma, which the body quickly replaces. If there is no response or poor response to plasma exchange, some studies suggest that intravenous infusions of immunoglobulins (IvIg therapy) may be beneficial.[1][3]

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.

Where to Start

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Merck Manual for health care professionals provides information on Isaacs' syndrome.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Isaacs' syndrome. Click on the link to view a sample search on this topic.


  1. NINDS Isaac's Syndrome Information Page. National Institute of Neurological Disorders and Stroke (NINDS). September 2015; https://www.ninds.nih.gov/Disorders/All-Disorders/Isaacs-syndrome-Information-Page.
  2. Suying Song. Myokymia. Medscape Reference. November 2014; https://emedicine.medscape.com/article/1141267-overview.
  3. Ahmed A, Simmons Z. Isaacs syndrome: A review. Muscle Nerve. July 2015; 52(1):5-12.
  4. Acquired Neuromyotonia. NORD. 2014; https://rarediseases.org/rare-diseases/acquired-neuromyotonia/.

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