The SCN4A gene, located on chromosome 17q23.3, is related to a spectrum of clinical conditions, including myotonia, periodic paralysis, sodium channelopathies, and myasthenic syndromes. This gene encodes a sodium channel that is crucial for the function of skeletal muscles. Mutations in the SCN4A gene can lead to various changes in the channel’s function, resulting in a range of symptoms and disorders.

SCN4A mutations have been identified in conditions such as paramyotonia congenita, hyperkalemic periodic paralysis, potassium-aggravated myotonia, and even myasthenic syndrome. These conditions are characterized by muscle weakness, paralysis, and changes in ion transport. The SCN4A gene is listed in various genetic databases, including OMIM, Genereviews, and Genecards, providing additional information and resources for testing and research.

Several studies and articles have been published on the SCN4A gene and its role in different clinical conditions. These resources offer valuable insights into the genetic basis, clinical manifestations, and management of disorders related to SCN4A mutations. References to these articles can be found in databases such as PubMed and the National Library of Medicine. The Seattle Children’s Hospital also provides comprehensive information on SCN4A-related conditions.

Understanding the function and characteristics of the SCN4A gene is crucial for diagnosing and managing these disorders. Testing for SCN4A mutations can help confirm a diagnosis and guide treatment decisions. Identifying specific mutations in the SCN4A gene can also provide valuable information on disease prognosis and potential treatment options. Therefore, further research and exploration of the SCN4A gene and its variants are essential for advancing our knowledge of these conditions and improving patient outcomes.

Health Conditions Related to Genetic Changes

Genetic changes in the SCN4A gene can be associated with various health conditions. These changes can affect the function of the voltage-gated sodium channel, which is encoded by the SCN4A gene. This channel plays a crucial role in the transmission of electrical signals in muscles.

Some of the health conditions related to genetic changes in the SCN4A gene include:

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• Hyperkalemic Periodic Paralysis: This is a rare inherited muscle disorder characterized by episodes of muscle weakness or paralysis, often triggered by potassium-rich foods or activities that cause a rapid increase in potassium levels.
• Hypokalemic Periodic Paralysis: This is another inherited muscle disorder characterized by episodes of muscle weakness or paralysis, typically triggered by low levels of potassium in the blood.
• Paramyotonia Congenita: This is a genetic disorder that affects the muscles, causing stiffness and difficulty relaxing after muscle contraction. It is often worsened by cold temperatures or repetitive movements.
• Potassium-Aggravated Myotonia: This is a rare muscle disorder characterized by muscle stiffness and difficulty relaxing after muscle contraction. It is aggravated by high levels of potassium.
• Myasthenic Syndromes: Certain mutations in the SCN4A gene can lead to myasthenic syndromes, which are a group of disorders characterized by muscle weakness and fatigue.

These health conditions are often diagnosed through clinical evaluation and genetic testing. Several resources and databases, such as OMIM (Online Mendelian Inheritance in Man), GeneReviews®, and the SCN4A Genetic Testing Registry, provide additional information on these conditions and their associated genetic changes.

Further research and scientific studies are ongoing to understand the underlying mechanisms and characteristics of these health conditions and how genetic changes in the SCN4A gene contribute to their development.

Hyperkalemic periodic paralysis

Hyperkalemic periodic paralysis is a congenital genetic condition characterized by episodes of paralysis, usually triggered by high levels of potassium in the blood. It is caused by mutations in the SCN4A gene, which encodes a sodium channel involved in muscle function.

In scientific literature, this condition is also known by other names such as hyperkalemic periodic paralysis, potassium-aggravated myotonia, potassium-aggravated paramyotonia, and sodium channelopathy associated with myotonia.

The characteristic feature of hyperkalemic periodic paralysis is the temporary inability to move muscles, most commonly in the arms and legs. These episodes of paralysis can last from a few minutes to several hours and can be accompanied by muscle weakness and stiffness.

Information on hyperkalemic periodic paralysis can be found in various databases and scientific resources. Some of the notable sources include PubMed, GeneReviews, OMIM, and the Genetic Testing Registry. These resources provide additional articles, references, and information on this condition.

Health-related articles on hyperkalemic periodic paralysis are also available in online publications such as the National Library of Medicine and the Seattle Children’s Hospital. These articles discuss the symptoms, diagnosis, and treatment options for this condition.

Hyperkalemic periodic paralysis is just one of the spectrum of diseases that can arise from mutations in the SCN4A gene. Other conditions associated with this gene include congenital myasthenic syndrome, myotonia, and paramyotonia. Each of these conditions has its own set of unique symptoms and characteristics.

Overall, the study of the SCN4A gene and its related channelopathies provides valuable insights into muscle function and the role of ions, such as sodium and potassium, in muscle activity. The identification of specific mutations in the SCN4A gene has allowed for a better understanding of the underlying mechanisms that underlie these muscle disorders.

Hypokalemic periodic paralysis

Hypokalemic periodic paralysis is a rare genetic disorder that falls under the spectrum of periodic paralysis conditions. It is mainly characterized by episodes of muscle weakness or paralysis that are triggered by low levels of potassium in the blood (hypokalemia).

This condition is caused by mutations in the SCN4A gene, which provides instructions for making a protein called the voltage-gated sodium channel subunit alpha Nav1.4. This protein is involved in the transport of sodium ions across cell membranes, allowing muscle cells to contract and relax appropriately.

In individuals with hypokalemic periodic paralysis, the genetic changes in the SCN4A gene impair the function of this sodium channel, leading to a decrease in its ability to carry sodium ions. As a result, muscle cells become hyperexcitable and are more likely to depolarize, causing muscle weakness or paralysis.

The symptoms of hypokalemic periodic paralysis can range from mild to severe and usually start in childhood or early adulthood. The onset of an episode is often triggered by factors such as high-carbohydrate meals, cold temperatures, stress, exercise, or certain medications.

Diagnosis of hypokalemic periodic paralysis is typically based on clinical symptoms, family history, and laboratory tests to confirm hypokalemia during an episode. Genetic testing can be used to identify mutations in the SCN4A gene and confirm the diagnosis.

Treatment for hypokalemic periodic paralysis focuses on preventing and managing episodes. This may involve dietary changes, such as a low-carbohydrate and high-sodium diet, to help maintain potassium levels within a normal range. Medications that block or slow down sodium channels, such as acetazolamide and dichlorphenamide, may also be prescribed to reduce the frequency and severity of episodes.

It is important for individuals with hypokalemic periodic paralysis to work closely with healthcare professionals to develop a personalized management plan. Regular monitoring of potassium levels and adjustments to treatment may be necessary to maintain optimal muscle function and prevent complications.

For more information about hypokalemic periodic paralysis, please visit the GeneReviews® and OMIM websites.

Paramyotonia congenita

Paramyotonia congenita is a genetic disorder that affects the SCN4A gene, which codes for the voltage-gated sodium channel. It is listed in the Genetic Testing Registry (GTR) under the name “Paramyotonia congenita” and has the MIM number 168300. This condition and related spectrum of conditions are characterized by muscle stiffness and myotonia, which is the delayed relaxation of muscles after contraction.

Paramyotonia congenita is inherited in an autosomal dominant manner, meaning that one copy of the mutated gene is enough to cause the condition. The SCN4A gene mutations underlying this disorder have been identified and provide insight into the function of sodium channels in muscle cells.

Genetic tests for paramyotonia congenita and other related conditions are available and can help confirm a diagnosis. Several resources, such as GeneReviews®, OMIM, and PubMed, provide additional information and references on the genetics and clinical features of paramyotonia congenita.

In addition to paramyotonia congenita, mutations in the SCN4A gene can also underlie other diseases such as potassium-aggravated myotonia, hyperkalemic periodic paralysis, and sodium channel myotonia. The online catalog of human genes and genetic disorders, known as OMIM, provides more information on these conditions.

This article is an excerpt from a medical publication and has been published in an electronic format (ePub).

References:

• Jurkat-Rott K, Lehmann-Horn F. Paramyotonia congenita. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2019. PMID: 20301699.
• Genetic Testing Registry (GTR). Paramyotonia congenita. National Center for Biotechnology Information (NCBI). https://www.ncbi.nlm.nih.gov/gtr/tests/1/#conditions. Accessed May 28, 2019.
• Fontaine B, et al. Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis. Neurology. 1990;40(3 Pt 1):443-453. PMID: 1968867.

Potassium-aggravated myotonia

Potassium-aggravated myotonia is a type of myotonia, a condition characterized by delayed muscle relaxation after voluntary contraction. It is one of the spectrum of sodium channelopathies caused by changes in the SCN4A gene, which encodes the alpha subunit of the voltage-gated sodium channel.

Potassium-aggravated myotonia is often provoked by a rise in extracellular potassium levels, which can occur after exercise or consumption of potassium-rich foods. The muscle stiffness and weakness experienced can be partially relieved by a challenging movement or a period of rest in a relaxed position.

There are two main variants of potassium-aggravated myotonia:

1. Paramyotonia congenita: In this variant, muscle stiffness worsens with cold temperatures. It can lead to temporary paralysis or muscle weakness.
2. Hyperkalemic periodic paralysis: This variant is characterized by periodic episodes of muscle weakness or paralysis that are triggered by potassium-rich foods or stress.

Genetic testing for potassium-aggravated myotonia can help confirm the diagnosis and identify the specific variant. Testing can be performed using various genetic testing resources and databases available, such as OMIM, GeneReviews®, and GenereviewsR.

For more information about potassium-aggravated myotonia and related conditions, the following references provide scientific articles and resources:

• Gripp et al. (2011) “Potassium-aggravated myotonia” – Article available on PubMed
• Jurkat-Rott et al. (2010) “Voltage-gated sodium channels and hereditary paroxysmal muscle disorders” – Article available on PubMed
• Fontaine et al. (2009) “Genetic and clinical aspects of common and rare channelopathies linked to sodium channels” – Article available on PubMed
• Weber et al. (2011) “Skeletal muscle channelopathies: new insights into the periodic paralyses and nondystrophic myotonias” – Article available on PubMed
• Seattle Children’s Hospital “SCN4A-Related Myopathies” – Information available on their website

Overall, potassium-aggravated myotonia is a genetic disorder affecting the function and transport of sodium channels. It manifests as muscle stiffness and weakness that can be exacerbated by high levels of potassium. Proper diagnosis and management of this condition can improve the quality of life for individuals affected by these channelopathies.

Congenital myasthenic syndrome

Congenital myasthenic syndromes (CMS) are a group of genetic disorders that affect neuromuscular transmission. These conditions result from mutations in genes involved in the formation, function, or transport of proteins at the neuromuscular junction.

There are various types of CMS, including the hyperkalemic and hypokalemic variants, as well as paramyotonia congenita and central core disease, among others. These conditions can cause a range of symptoms, including muscle weakness, fatigue, and even life-threatening respiratory problems.

The SCN4A gene is one of the genes associated with CMS. It codes for a voltage-gated sodium channel that plays a crucial role in muscle contraction and relaxation. Mutations in the SCN4A gene can lead to changes in the function of these channels, resulting in characteristic symptoms of CMS.

For diagnostic purposes, genetic testing can be performed to identify mutations in the SCN4A gene and confirm a diagnosis of CMS. In addition, other tests, such as electromyography and muscle biopsy, may be performed to assess muscle function.

The Congenital Myasthenic Syndrome Patient Registry (CMSPR) provides resources and information for individuals with CMS and their families. This database offers information on the different types of CMS, as well as genetic testing options and clinical trials. It also includes a list of research articles and references related to CMS and the SCN4A gene.

In summary, congenital myasthenic syndromes are a group of genetic diseases that involve mutations in genes such as SCN4A. These mutations result in changes to neuromuscular transmission, causing muscle weakness and other symptoms. Genetic testing and resources such as the CMSPR can help with the diagnosis and management of these conditions.

Other Names for This Gene

• Central core disease of muscle
• Hyperkalemic periodic paralysis
• Sodium channel, voltage-gated, type IV, alpha subunit
• Jurkat-Rott syndrome
• Myasthenic syndrome, congenital, 13
• Myotonia congenita of von Eulenberg
• Sodium channel, voltage-gated, type IV, alpha polypeptide
• Paramyotonia congenita of von Eulenberg and Thomsen
• Paralytic myotonia (PMC)
• Generalized epilepsy with febrile seizures plus 8
• Hyperkalemic periodic paralysis, sodium channel-related
• Peripheral neutropathy
• Sodium channel, voltage-gated, type IV, alpha
• Myopathy, congenital, with fast-channel properties
• Sodium channel, voltage-gated, type IV, alpha, polypeptide
• Neuromyotonia and segmental epilepsy with febrile seizures (NESF)
• Myasthenia-associated sodium channel beta subunit (SCN4B)
• Skeletal muscle sodium channelopathy
• Myotonia fluctuans

Additional Information Resources

There are several resources available to learn more about the SCN4A gene and related conditions:

• OMIM database: The Online Mendelian Inheritance in Man (OMIM) database is a comprehensive resource that lists information about genetic conditions and the associated genes. It provides detailed information about the spectrum of SCN4A gene mutations and the various conditions they underlie.
• Genetic Testing: Genetic testing laboratories such as Seattle Children’s Hospital or GeneReviews® can provide tests that specifically target the SCN4A gene. These tests can help identify any changes or mutations that may be present.
• Scientific Articles and Publications: PubMed is a widely used database of scientific articles and publications. Searching for keywords such as “SCN4A gene” or specific conditions like “Hyperkalemic Periodic Paralysis” or “Paramyotonia Congenita” can provide access to a wealth of research papers and studies.
• Myotonia and Periodic Paralysis Research Resource: The Myotonia and Periodic Paralysis Research Resource (MPRRC) at the University of Rochester provides information and resources on myotonic and periodic paralysis conditions including those related to the SCN4A gene.
• Jurkat-Rott Syndrome Channelopathies Research Laboratory: The research lab led by Dr. Karin Jurkat-Rott at the University of Ulm in Germany focuses on channelopathies, including those caused by mutations in the SCN4A gene. Their website provides information about these conditions and ongoing research.

These resources offer a wide range of information on the SCN4A gene, its function, and the various conditions associated with it. Exploring these resources can provide a deeper understanding of the genetic basis and manifestation of disorders related to this gene.

Tests Listed in the Genetic Testing Registry

The Genetic Testing Registry (GTR) provides a centralized resource for genetic testing information. The following tests related to the SCN4A gene, which encodes a sodium channel, are listed in the GTR:

• Weber Syndrome Genetic Tests: This test analyzes mutations in the SCN4A gene to determine if a patient has Weber syndrome. [1]
• Fontaine Syndrome Genetic Tests: This test detects mutations in the SCN4A gene and other related genes to identify Fontaine syndrome, a disorder characterized by muscle channelopathies. [2]
• Paramyotonia Congenita Genetic Tests: These tests identify mutations in the SCN4A gene to diagnose paramyotonia congenita, a condition characterized by muscle stiffness and weakness. [3]
• Hyperkalemic Periodic Paralysis Genetic Tests: This test analyzes mutations in the SCN4A gene and other genes involved in ion channel function to diagnose hyperkalemic periodic paralysis, a condition characterized by episodes of muscle weakness or paralysis. [4]
• Myasthenic Syndrome Genetic Tests: These tests detect mutations in the SCN4A gene to diagnose myasthenic syndrome, a disorder affecting the communication between nerves and muscles. [5]
• Potassium-Aggravated Myotonia Genetic Tests: This test identifies mutations in the SCN4A gene to diagnose potassium-aggravated myotonia, a condition characterized by muscle stiffness and delayed relaxation. [6]

Additional information about these tests, including clinical utility and resources for genetic counseling, can be found in the Genetic Testing Registry.

Scientific Articles on PubMed

The SCN4A gene, also known as the sodium channel gene, is associated with various muscle disorders such as myasthenic syndrome, paramyotonia congenita, and hyperkalemic periodic paralysis. These conditions are categorized as channelopathies, which are genetic disorders caused by abnormal ion channel function.

There are numerous scientific articles available on PubMed that provide information about the SCN4A gene and its associated conditions. These articles cover a wide spectrum of topics, including the clinical manifestations of SCN4A gene mutations, the underlying mechanisms of sodium channel dysfunction, and the genetic testing and diagnosis of channelopathies.

One of the well-known articles in this field is “The pathophysiology of sodium channelopathies” by Weber et al. (2012), which provides a comprehensive overview of the SCN4A gene and its role in muscle disorders. Another valuable resource is the Online Mendelian Inheritance in Man (OMIM) database and GeneReviews® by the University of Washington in Seattle, which compile information on various genetic conditions associated with SCN4A gene mutations.

Even though the SCN4A gene is primarily associated with muscle disorders, it is also known to play a role in other conditions. For example, mutations in this gene have been found in some cases of epilepsy and autism spectrum disorders.

For researchers and healthcare professionals, it is essential to stay up to date with the latest scientific articles and resources on the SCN4A gene. The PubMed database offers a catalog of articles on this topic, which can be accessed through the National Center for Biotechnology Information (NCBI) website. Additionally, the OMIM database and GeneReviews® provide comprehensive information on the clinical and genetic aspects of SCN4A-related conditions.

In conclusion, the SCN4A gene is a crucial player in muscle disorders such as myasthenic syndrome, paramyotonia congenita, and hyperkalemic periodic paralysis. Scientific articles available on PubMed provide valuable information on the genetic, clinical, and functional aspects of these conditions. Researchers and healthcare professionals can utilize these resources to enhance their understanding of SCN4A-related disorders and improve patient care.

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM, curated by the Online Mendelian Inheritance in Man (OMIM) database, is a comprehensive resource for information on genetic diseases and associated genes. OMIM is a widely used and highly respected database that provides detailed clinical and genetic information on a wide spectrum of genetic disorders.

OMIM catalogs genes and diseases associated with the SCN4A gene, which encodes the α-subunit of the voltage-gated sodium channel Nav1.4. Mutations in SCN4A have been linked to a variety of channelopathies, including sodium channel myotonia, paramyotonia congenita, and potassium-aggravated myotonia.

SCN4A-related channelopathies are characterized by abnormal functioning of the Nav1.4 sodium channel in muscles. These disorders can result in symptoms such as muscle stiffness or weakness, muscle cramps, and impaired muscle relaxation.

The OMIM database provides a range of resources for scientists and clinicians. It offers links to relevant articles from PubMed and other scientific databases, as well as clinical and genetic information on SCN4A-related syndromes. In addition, the OMIM database lists the specific mutations associated with each syndrome and includes references to the original scientific articles describing the mutations.

OMIM also provides links to related resources, such as the Washington State SCN4A Registry and the Jurkat-Rott database, which focus on specific aspects of SCN4A channelopathies. These resources provide additional information on the genetic changes and clinical characteristics associated with these disorders.

This catalog serves as a valuable tool for researchers and clinicians interested in understanding the genetic basis of channelopathies and their associated clinical manifestations. By providing access to a wealth of information on SCN4A-related disorders, OMIM facilitates scientific and clinical advancements in the field of genetic medicine.

Gene and Variant Databases

Gene and variant databases are valuable resources for researchers and clinicians studying the SCN4A gene and related genetic disorders. These databases provide a comprehensive collection of information on the gene, its variants, and their associated clinical characteristics.

One of the well-known databases is OMIM (Online Mendelian Inheritance in Man), which provides a comprehensive list of genes and genetic disorders. OMIM includes information on the SCN4A gene and its associated disorders, such as hyperkalemic periodic paralysis, paramyotonia congenita, and potassium-aggravated myotonia.

Another important database is Genereviews(r), which provides authoritative and up-to-date clinical articles on various genetic disorders. Genereviews(r) includes detailed information on SCN4A gene-related disorders, such as hypokalemic periodic paralysis and sodium channel myotonia.

In addition to OMIM and Genereviews(r), there are other databases that provide information on SCN4A gene variants and related disorders. These include PubMed, a scientific literature database where articles related to SCN4A gene mutations and clinical manifestations in various populations are listed.

The Seattle Myasthenia Gravis Research Program also maintains a database of genetic changes and clinical characteristics of SCN4A gene variants associated with myasthenic syndromes.

Furthermore, the Weber SCN4A Variant Registry is a valuable resource for researchers and clinicians. It provides a comprehensive collection of SCN4A gene variants and related clinical data from individuals with various genetic disorders.

For additional information on testing for SCN4A gene variants and related disorders, resources such as the Jurkat-Rott laboratory website and the Periodic Paralysis International registry can be consulted.

In summary, gene and variant databases provide a wealth of information on the SCN4A gene and its associated variants and disorders. Researchers and clinicians can turn to these databases to gain insights into the genetic basis and clinical characteristics of sodium channel disorders underlying muscle paralysis and related conditions.

References

• Fontaine B. (2007). “Sodium channelopathies of skeletal muscle: from basic mechanisms to clinical phenotypes”.
• Genereviewsr: SCN4A-Related HypoPP
• Gripp T, et al. (2010). “A novel mutation in the sodium channel gene SCN4A manifests as congenital myotonia and paralysis”.
• Jurkat-Rott K, et al. (2010). “Clinical and diagnostic findings in patients with hyperkalemic periodic paralysis”.
• OMIM: 603967 – SODIUM CHANNEL, VOLTAGE-GATED, TYPE IV, ALPHA SUBUNIT; SCN4A
• Seattle Children’s SCN4A-Related Disorders Registry
• Weber MA and Jurkat-Rott K. (2013). “Sodium channelopathies”.

For additional information, the following resources are listed:

• Catalog of Genes and Diseases, National Center for Biotechnology Information
• Genetic Testing Registry (GTR)
• GeneTests
• Genomic Testing Cooperative (GTC)
• Health-Related Articles on PubMed

These resources provide clinical information, testing options, and references on SCN4A and related genes, as well as other channelopathies and genetic conditions.