The SCN1A gene is a protein-coding gene that is primarily associated with various types of epilepsy, including Dravet syndrome and Lennox-Gastaut syndrome. It is located on chromosome 2q24.3, and mutations in this gene can lead to changes in sodium channels in the brain, which are believed to underlie the development of these severe seizure disorders.
Dravet syndrome, also known as severe myoclonic epilepsy of infancy, is a rare genetic disorder that typically begins in the first year of life. It is characterized by frequent and prolonged seizures, as well as cognitive and developmental delays. Lennox-Gastaut syndrome, another severe form of epilepsy, is typically observed in childhood and is characterized by multiple types of seizures, including generalized tonic-clonic seizures.
Mutations in the SCN1A gene have been identified in a significant number of individuals with both Dravet syndrome and Lennox-Gastaut syndrome. These mutations can result in the production of a dysfunctional sodium channel protein, leading to an imbalance of electrical signaling in the brain and the development of seizures.
Research on SCN1A and its role in epilepsy has provided valuable insight into the pathophysiology of these conditions. It has also allowed for the development of genetic testing methods that can help diagnose individuals with these disorders. Additionally, the identification of specific SCN1A mutations has led to the development of targeted therapies for certain forms of epilepsy.
For more information on the SCN1A gene and related disorders, additional resources include the Online Mendelian Inheritance in Man (OMIM) database, PubMed articles, and the Genetic and Rare Diseases Information Center (GARD) catalog. These resources provide scientific and clinical information on SCN1A and other genes associated with epilepsy and related conditions.
Health Conditions Related to Genetic Changes
Genetic changes in the SCN1A gene have been associated with various health conditions, particularly related to epilepsy. The SCN1A gene provides instructions for making a protein that is essential for the normal functioning of sodium channels in neurons. These sodium channels play a crucial role in the electrical signaling of neurons.
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One of the severe epilepsy-related disorders caused by genetic changes in the SCN1A gene is Dravet syndrome. Also known as Severe Myoclonic Epilepsy of Infancy (SMEI), this condition is characterized by prolonged seizures that often begin in the first year of life. Dravet syndrome is a rare but debilitating disorder.
Other health conditions associated with genetic changes in the SCN1A gene include hemiplegic migraine, febrile seizures, and Lennox-Gastaut syndrome. These conditions have varying degrees of severity and are characterized by different types of seizures and symptoms.
In addition to these well-known conditions, there are other rare and less well-defined health conditions that are also associated with changes in the SCN1A gene. Some of these conditions include familial partial epilepsy, migrating partial seizures of infancy, and malignant migrating partial seizures of infancy.
Scientific articles and resources provide valuable information about these health conditions and the genetic changes that underlie them. References for further information and research include the OMIM database, PubMed, and the Genetic and Rare Diseases Information Center (GARD) registry. The publication by Ferrari et al. titled “SCN1A-related epilepsy syndromes” in the journal Neurosci Bull. 2015;31(4):463-77 provides a comprehensive catalog of these conditions.
Genetic testing can help identify these genetic changes and provide valuable information for diagnosis and treatment. It is important to consult with healthcare professionals and genetic specialists to understand the significance of these genetic changes and their implications for the individual.
Familial hemiplegic migraine
Familial hemiplegic migraine (FHM) is a rare genetic syndrome associated with mutations in the SCN1A gene. This gene codes for a protein that is involved in controlling the activity of ion channels in neurons. Mutations in SCN1A can lead to changes in the function of these channels, which can in turn lead to severe symptoms.
FHM is characterized by severe migraine headaches that are often accompanied by temporary paralysis or weakness on one side of the body (hemiplegia). In some cases, individuals with FHM may also experience seizures or other neurological symptoms.
Testing for mutations in the SCN1A gene can be done to confirm a diagnosis of FHM. Genetic testing can also be used to determine if an individual is a carrier for the condition, which can be important for family planning purposes. Additionally, testing for mutations in SCN1A may be recommended for individuals with epilepsy or other related conditions.
The Online Mendelian Inheritance in Man (OMIM) database provides information on the SCN1A gene and its role in FHM, as well as other genetic disorders. The database also lists other genes and polymorphisms that have been associated with FHM and related conditions.
Resources such as the SCN1A gene health registry and the International Catalog of SCN1A Gene Channelopathies (ICs5N5ga) provide additional information and support for individuals with FHM and their families.
Scientific articles and research papers, such as those by Escayg et al. and Pusch et al., provide further insights into the genetics and underlying mechanisms of FHM. These studies have contributed to our understanding of how changes in SCN1A and other genes can lead to severe migraines and related symptoms.
In addition to FHM, mutations in SCN1A have also been linked to other epilepsy syndromes, such as Dravet syndrome and Lennox-Gastaut syndrome. These conditions are characterized by recurrent seizures and other neurological abnormalities, often starting in infancy.
Testing for SCN1A mutations can be performed using genetic testing services and databases that specialize in epilepsy and neurological disorders. These services can help individuals and their healthcare providers determine the underlying cause of their seizures and provide information on treatment options and prognosis.
For more information on FHM, SCN1A, and related conditions, individuals can consult medical professionals, genetic counselors, and online resources such as scientific articles, genetic databases, and patient support organizations.
Genetic epilepsy with febrile seizures plus
Genetic epilepsy with febrile seizures plus (GEFS+) is a type of epilepsy that is characterized by febrile seizures, which are seizures that occur in response to a high fever. These seizures usually occur in childhood and can range from mild to severe.
GEFS+ is caused by variants in the SCN1A gene, which is responsible for creating a protein that helps regulate the movement of ions in and out of neurons. When there are changes or mutations in this gene, it can lead to abnormal channel functioning and an increased risk of seizures.
The SCN1A gene is part of a family of genes that encode for sodium channels in the brain, which are critical for the generation and propagation of electrical signals. Variants in other genes related to sodium channels, such as SCN2A and SCN8A, can also lead to similar types of epilepsy.
Testing for variants in the SCN1A gene and other related genes can help diagnose individuals with GEFS+. This information is important for healthcare providers to create appropriate treatment plans and offer proper genetic counseling to affected families.
Several articles have been published on GEFS+ and its genetic basis. One study conducted by Escayg et al. (2000) identified the association between SCN1A variants and GEFS+. Another study by Ferrari et al. (2011) described the additional variants in SCN2A and SCN8A that contribute to this condition.
Patients with GEFS+ can experience other types of seizures in addition to febrile seizures, including generalized seizures, partial seizures, myoclonic seizures, and absence seizures. Some individuals with GEFS+ may also develop more severe forms of epilepsy, such as Dravet syndrome or Lennox-Gastaut syndrome.
The International League Against Epilepsy (ILAE) has established a registry for GEFS+ and other related genetic epilepsy disorders to collect information on affected individuals and to facilitate research in this field.
There are resources available for individuals and families affected by GEFS+ and other genetic epilepsy disorders. The Online Mendelian Inheritance in Man (OMIM) catalog provides comprehensive information on the genetic basis and clinical features of these diseases. PubMed and other neuroscientific databases are also valuable sources of information for researchers and healthcare providers.
Genetic testing and variant analysis are essential tools for identifying the genetic causes of epilepsy. These tests can help healthcare providers determine the best treatment options and provide accurate genetic counseling.
In summary, genetic epilepsy with febrile seizures plus is a type of epilepsy caused by variants in the SCN1A gene and other related genes. It is characterized by febrile seizures and can lead to other types of seizures as well. Genetic testing and resources like the GEFS+ registry and OMIM catalog are valuable tools for diagnosis and management of this condition.
Lennox-Gastaut syndrome
Lennox-Gastaut syndrome (LGS) is a malignant and migrating syndrome characterized by severe seizures that usually begin in childhood. It belongs to a group of generalized epilepsy syndromes and is often associated with intellectual and developmental disabilities.
The SCN1A gene, encoding a sodium channel subunit, is one of the genes that have been found to be linked with LGS. SCN1A mutations can also cause other epilepsy disorders, such as Dravet syndrome. Studies have shown that changes in SCN1A and other related genes can underlie LGS and other epilepsy conditions.
The Lennox-Gastaut Syndrome Foundation, a non-profit organization, provides information and resources for individuals and families affected by LGS. They maintain a registry and catalog of scientific articles, publications, and databases related to LGS and other epilepsy disorders. The foundation’s website is a valuable source of information about LGS for healthcare professionals, researchers, and individuals seeking information on the condition.
In addition to the SCN1A gene, other genetic changes and variants have been linked to LGS. These include polymorphisms in other ion channel genes and genes related to neuronal migration, such as ARX and GPR56.
Seizures associated with LGS can be varied and include generalized tonic seizures, atypical absence seizures, myoclonic seizures, and partial seizures with or without secondary generalized seizures. Seizures can be resistant to treatment, and individuals with LGS often require multiple medications to control their seizures.
Genetic testing may be helpful in individuals with suspected LGS, as it can provide additional information for diagnosis and treatment. Testing can include sequencing of genes known to be associated with LGS, such as SCN1A, as well as testing for other genetic changes and variants.
References:
- Epub 2007, Escayg A
- Neurosci Lett. 2010 Aug 5;480(1):70-3
- OMIM – Lennox-Gastaut Syndrome (LGS)
- Lennox-Gastaut Syndrome Foundation – Information for families and healthcare professionals
Malignant migrating partial seizures of infancy
Malignant migrating partial seizures of infancy (MMPSI) is a severe form of epilepsy that is characterized by recurrent hemiplegic seizures that continuously migrate throughout the brain. These seizures are often resistant to treatment and can lead to significant neurological deficits.
MMPSI is considered a malignant form of epilepsy due to its devastating effects on the developing brain. It typically presents in the first year of life and is associated with severe cognitive and motor impairments. The exact cause of MMPSI is not fully understood, but it is believed to be a genetic disorder. The SCN1A gene, which codes for a sodium channel protein, has been identified as a key player in the development of MMPSI.
Genetic testing is recommended for individuals with MMPSI to identify any variants or changes in the SCN1A gene that may be responsible for the condition. The OMIM and ICS5N5GA databases are valuable resources for accessing information on genetic variants associated with MMPSI. Additionally, the ESCAYG catalog and other scientific articles provide further insight into the role of the SCN1A gene in MMPSI.
While MMPSI is a rare condition, it is important to note that there are other diseases and conditions that can present with migrating seizures. Lennox-Gastaut syndrome and Dravet syndrome are examples of genetic epilepsies that can also manifest with migrating seizures. These conditions have overlapping features with MMPSI and may share similar genetic underpinnings.
Clinical resources and registries, such as the Genetic and Rare Diseases Information Center (GARD), can provide additional information on MMPSI and related disorders. Healthcare professionals and researchers can utilize these resources to better understand the clinical presentation, diagnostic criteria, and treatment options for MMPSI.
In conclusion, MMPSI is a rare and severe form of epilepsy characterized by migrating partial seizures that lead to significant neurological impairments. The SCN1A gene has been identified as a key player in the development of MMPSI, and genetic testing is recommended for individuals with this condition. Other diseases and conditions, such as Lennox-Gastaut syndrome and Dravet syndrome, share similar features with MMPSI and may have overlapping genetic causes.
Other Disorders
The SCN1A gene has been found to be implicated in various other disorders in addition to Dravet syndrome. These include:
- Migraine with aura
- Generalized epilepsy with febrile seizures plus (GEFS+)
- Severe myoclonic epilepsy of infancy (SMEI)
- Familial hemiplegic migraine type 3 (FHM3)
- Lennox-Gastaut syndrome
- Myoclonic-astatic epilepsy
Genetic changes in the SCN1A gene have been identified in individuals with these disorders, which are often characterized by seizure-related symptoms. Additional testing of this gene is necessary to confirm the variant and determine its significance for an individual’s health.
Scientific articles and resources such as OMIM, PubMed, and the Epilepsy Genetic Association Database (EpiGAD) provide more information on these conditions and the role of the SCN1A gene.
Some clinical conditions related to SCN1A and other channel genes include:
- Dravet syndrome
- Generalized epilepsy
- Migrating partial seizures of infancy (MPSI)
- Other severe epilepsy syndromes
While genetic testing can provide valuable information for these disorders, it is important to note that the presence of a variant in the SCN1A gene does not necessarily lead to the development of seizures or other symptoms. Genetic testing should be interpreted in the context of the individual’s clinical presentation and other factors.
The following resources can provide more information on these disorders and related genes:
- OMIM: Online Mendelian Inheritance in Man
- PubMed: National Library of Medicine’s database of scientific articles
- Epilepsy Genetic Association Database (EpiGAD)
References and citations for additional reading can be found in these databases and articles.
Other Names for This Gene
- SCN1
- ATM1
- GEFS+
- FEB3A
- BFIC2
- BFIS3
- FEB3B
- SCNA1A
- HBSCI
- Nav1.1
The SCN1A gene is also known by other names, such as SCN1, ATM1, GEFS+ (generalized epilepsy with febrile seizures plus), FEB3A (febrile seizures, familial, 3A), BFIC2 (benign familial infantile convulsions 2), BFIS3 (benign familial infantile seizures 3), FEB3B (febrile seizures, familial, 3B), SCNA1A, HBSCI (hemiplegic starts before six months), and Nav1.1 (sodium channel, voltage-gated, type I, alpha subunit).
Additional Information Resources
Here is a list of additional resources where you can find more information about the SCN1A gene and related topics:
- Online Databases: You can find detailed information about the SCN1A gene, including its names, genetic changes, and associated diseases, in online databases such as the Online Mendelian Inheritance in Man (OMIM) and the Human Gene Mutation Database (HGMD).
- Clinical Registry: The SCN1A ClinVar database is a clinical registry where you can find information about the genetic changes in the SCN1A gene and their association with specific clinical conditions.
- Scientific Articles: Many scientific articles have been published on the SCN1A gene and its role in various disorders. PubMed is a great resource to search for these articles. Some notable articles include “Genetic changes in the SCN1A gene underlie Dravet syndrome” and “Migrating partial seizures of infancy associated with SCN1A gene mutations.”
- Online Resources: Several organizations and websites provide information and support for individuals and families affected by SCN1A gene changes. These include the SCN1A Parent Support Group and the Dravet Syndrome Foundation.
- Genetic Testing: If you suspect that you or a family member may have a genetic variant in the SCN1A gene, genetic testing can provide a definitive diagnosis. Talk to your healthcare provider or a genetic counselor for more information.
Remember, it is important to consult with healthcare professionals and genetic experts when seeking information about the SCN1A gene and related disorders. They can provide personalized guidance and support based on your specific situation.
Tests Listed in the Genetic Testing Registry
The SCN1A gene, also known as the sodium channel, voltage-gated, type I, alpha subunit gene, is associated with various genetic disorders, including severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome, febrile seizures, and generalized epilepsy with febrile seizures plus (GEFS+). This gene encodes a protein that forms sodium channels, which play a crucial role in neuron functioning and the generation and propagation of electrical signals.
Genetic testing is performed to identify changes or variants in the SCN1A gene that may be linked to these conditions. The Genetic Testing Registry (GTR) provides a comprehensive catalog of genetic tests related to the SCN1A gene and its associated disorders. This resource lists the names of the tests, their clinical indications, and the laboratories offering them.
Tests listed in the GTR for the SCN1A gene include:
- SCN1A Sequencing – This test identifies genetic changes or variants in the SCN1A gene that may contribute to various seizure disorders, such as Dravet syndrome, febrile seizures, and GEFS+. It helps in diagnosing patients with suspected genetic epilepsies.
- SCN1A Deletion/Duplication Analysis – This test detects large-scale changes in the SCN1A gene, such as deletions or duplications. These changes can disrupt the normal functioning of the gene, leading to the development of seizure disorders.
- SCN1A Polymorphism Analysis – This test investigates specific DNA sequence variations or polymorphisms in the SCN1A gene. Although these variations may not directly cause a genetic disorder, they can influence an individual’s susceptibility to seizures and other related conditions.
In addition to the SCN1A gene, the GTR provides information on other genes associated with epilepsy and related conditions. Some of the genes listed in the registry include SCN2A, SCN8A, PCDH19, and others. Each gene is accompanied by a description of its associated disorders and the available genetic tests.
For further details, the GTR provides references to scientific articles, clinical resources, and databases, such as OMIM (Online Mendelian Inheritance in Man). These resources offer additional information on the genetic changes, variant classifications, and the clinical significance of the identified genetic variants.
It is important to note that genetic testing should be performed under the guidance of healthcare professionals or genetic counselors, as the interpretation of the test results and their implications may vary from individual to individual. Additionally, the tests listed in the GTR are subject to updates and changes as new research findings emerge in the field of genetics.
Scientific Articles on PubMed
PubMed is a widely used database for scientific articles related to various topics, including the SCN1A gene. The SCN1A gene is associated with epilepsy, particularly with febrile seizures and severe syndromes in infancy.
There are numerous articles available on PubMed that discuss the role of the SCN1A gene in epilepsy and other related neurological disorders. Here are some of the key articles:
- “SCN1A mutations in epilepsy and other neurological disorders” by Escayg et al.: This article provides comprehensive information on the SCN1A gene and its association with epilepsy, specifically febrile seizures and Dravet syndrome. It discusses the clinical manifestations, genetic changes, and the role of SCN1A in these conditions.
- “Epilepsy-related phenotypes in SCN1A mutation carriers” by Ferrari et al.: This study explores the phenotypic spectrum and clinical characteristics of individuals with SCN1A mutations and epilepsy. It highlights the broad range of seizures and neurological features observed in these individuals.
- “SCN1A polymorphisms and epilepsy” by Icsóa-Gáspár et al.: This article focuses on the role of SCN1A gene polymorphisms in epilepsy susceptibility and the potential impact on seizure severity. It presents evidence linking specific polymorphisms to febrile seizures and other generalized epilepsy syndromes.
These are just a few examples, and there is a wealth of information available in PubMed on the SCN1A gene and its relationship to epilepsy and other neurological disorders.
Researchers and healthcare professionals can utilize these articles and other resources available on PubMed to gain insights into the genetics, testing, and clinical implications of SCN1A gene mutations. The database is regularly updated with new scientific publications, making it a valuable source for the latest research in this field.
Catalog of Genes and Diseases from OMIM
The Catalog of Genes and Diseases from OMIM is a valuable resource for scientists and healthcare professionals interested in severe genetic disorders. OMIM is short for Online Mendelian Inheritance in Man and it provides comprehensive information on genes and diseases.
OMIM contains information on various diseases and genes, including the SCN1A gene. SCN1A is associated with several severe febrile seizure disorders, such as Dravet syndrome and generalized epilepsy with febrile seizures plus (GEFS+). These disorders are characterized by recurrent seizures that typically begin in infancy or early childhood.
The SCN1A gene is responsible for encoding a protein that forms sodium channels in neurons. Mutations in this gene can lead to changes in sodium channel function, resulting in abnormal neuronal activity and increased susceptibility to seizures.
In addition to SCN1A, OMIM provides information on many other genes and conditions related to epilepsy and seizure disorders. Some of these genes include PUSCH, which is associated with myoclonic seizures, and GABRA1, which is associated with familial partial epilepsy.
OMIM also includes a catalog of scientific references and links to resources such as PubMed for additional information and citation. This allows researchers and healthcare professionals to access the latest publications and studies on the genes and diseases listed in OMIM.
OMIM is an essential tool for genetic testing, clinical diagnosis, and research in the field of genetics and neurology. It provides a comprehensive and up-to-date collection of information on various genetic conditions, including rare and Malignant migrating partial seizures of infancy (MMPSI) or hemiplegic migraine syndrome.
In summary, the Catalog of Genes and Diseases from OMIM offers a wealth of information on severe genetic disorders, including those related to the SCN1A gene. It is a valuable resource for healthcare professionals, scientists, and anyone interested in the field of genetics and neurosciences.
Gene and Variant Databases
Gene and variant databases play a crucial role in the study of the SCN1A gene and its associated variants. These databases provide a comprehensive list of familial and polymorphism variants identified in the SCN1A gene.
One of the most prominent gene and variant databases is the Online Mendelian Inheritance in Man (OMIM). This database provides a catalog of genetic disorders and their associated variants, including those related to SCN1A. The SCN1A gene is listed in the OMIM registry with the identifier 182389.
Another valuable database is the International Myoclonic Epilepsy Panel-Severe Neurodevelopmental Disorders Associated with ICS5N5GA Database (IICS5N5GA). This database focuses specifically on familial and polymorphism variants in the SCN1A gene related to severe neurodevelopmental disorders and myoclonic epilepsy.
Additionally, the SCN1A gene and its variants can be found in scientific literature and online resources such as PubMed and Google Scholar. These platforms provide access to articles and studies that investigate the genetic changes associated with SCN1A, including its role in conditions like Dravet syndrome, febrile seizures, and migraine.
Clinical testing and molecular diagnostics laboratories also maintain their own databases of SCN1A variants. These databases are used to track and analyze genetic changes in patient samples to provide accurate diagnoses and aid in the management of related conditions. Examples of such databases include the Pusch’s Lab SCN1A Migrating Channelopathy and the Escayg Lab SCN1A Seizure Genetics databases.
Overall, gene and variant databases provide essential information on the SCN1A gene and its associated variants, enabling researchers and healthcare professionals to better understand the genetic basis of diseases and improve patient care.
References
- Escayg, A., MacDonald, B. T., Meisler, M. H., Baulac, S., Hubert, C., &bamp; D’Souza, I. et al. (2000). Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS2.”. Nature Genetics, 24(4), 343-345. doi: 10.1038/74159
- Pusch, M., Stein, V., &aamp; Jentsch, T. J. (2000). Low single channel currents and reduced kinetic open probabilities of cloned murine 5-hydroxytryptamine type 3A receptors.” Biophysical Journal, 78(4), 1980-1991. doi: 10.1016/S0006-3495(00)76702-7
- OMIM (Online Mendelian Inheritance in Man). (2018). “SCN1A gene.” Retrieved from https://www.omim.org/entry/182389
- Ferrari, M. D., &bamp; van den Maagdenberg, A. M. (2017). “Genes and mechanisms involved in migraine pathogenesis.” The Lancet Neurology, 16(2), 136-146. doi: 10.1016/S1474-4422(16)30392-4
