Genetic epilepsy with febrile seizures plus (GEFS+) is a rare genetic condition that causes a spectrum of seizures, including febrile seizures and various types of epilepsy. It has a complex inheritance pattern, which makes it difficult to diagnose and understand. However, several genes have been identified as playing a role in the condition, including the GABRG2 gene, which codes for a subunit of gamma-aminobutyric acid (GABA) receptors.
Researchers have discovered that mutations in the GABRG2 gene, as well as other genes such as SCN1A and SCN9A, can cause GEFS+. These mutations affect the function of ion channels in the brain, leading to abnormal electrical activity and seizures. While febrile seizures are a common symptom of GEFS+, other types of seizures can also develop, such as generalized tonic-clonic seizures and myoclonic seizures.
GEFS+ is usually associated with a family history of seizures, and it is often diagnosed in childhood. However, it can also develop in individuals with no family history of the condition. Genetic testing can be used to confirm a diagnosis of GEFS+ and to identify specific gene variants. Further testing and genetic counseling may be necessary to determine the inheritance pattern and provide more information about the condition.
There are resources available for patients and families affected by GEFS+, including advocacy organizations and support groups. These resources can provide information about the condition, available treatment options, and research opportunities. There are also scientific articles and citations available on PubMed and OMIM that provide more details about the causes, symptoms, and inheritance of GEFS+.
In conclusion, GEFS+ is a genetic condition characterized by a spectrum of seizures, including febrile seizures and various types of epilepsy. It is caused by mutations in genes such as GABRG2, SCN1A, and SCN9A. Genetic testing and counseling can help individuals with this condition learn more about its inheritance and development. Resources and support are available for patients and their families to help them navigate the challenges of living with GEFS+.
Frequency
The condition known as Genetic Epilepsy with Febrile Seizures Plus (GEFS+) is a relatively rare disease that is characterized by febrile seizures and additional seizure types, such as generalized, myoclonic, and partial seizures.
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GEFS+ is caused by variants in several different genes, primarily in the sodium channel subunit genes SCN1A and SCN9A, as well as the GABRG2 gene which codes for a subunit of the GABA-A receptor.
Researchers have studied the frequency of these genetic variants in patient populations and have found that they are more common in individuals with febrile seizures plus, compared to those with other forms of epilepsy or febrile seizures alone.
In an article by Escayg et al., it was reported that variants in the SCN1A gene were found in about 31% of patients with GEFS+, while variants in the GABRG2 gene were found in about 8% of patients. Variants in other genes were less common, with frequencies ranging from 1-3%.
It is important to note that these frequencies may vary depending on the population studied and other factors, and additional research is needed to fully understand the frequency of these genetic variants.
The Genetic Epilepsy with Febrile Seizures Plus (GEFS+) International Family Registry and DNA Blood Samples Resource Center is a valuable resource for researchers studying this condition. The center provides support and resources for families affected by GEFS+ and collects DNA samples for genetic testing and research purposes.
For more information about the frequency of genetic variants in GEFS+ and other forms of epilepsy, researchers and healthcare professionals can refer to the Online Mendelian Inheritance in Man (OMIM) catalog, which provides comprehensive information about genetic disorders.
Advocacy organizations, such as the Dravet Syndrome Foundation, also provide resources and support for individuals and families affected by GEFS+ and related conditions.
Causes
Genetic epilepsy with febrile seizures plus (GEFS+) is a rare condition that is caused by mutations in certain genes that are involved in the function of ion channels in the brain. These ion channels are responsible for controlling the flow of electrical signals in the brain, and mutations in these genes can disrupt this process and lead to seizures.
One of the most common genes associated with GEFS+ is called SCN1A, which encodes a protein known as Nav1.1. Mutations in this gene are also associated with another form of epilepsy called Dravet syndrome, which is characterized by severe seizures that often begin in infancy. Mutations in other ion channel genes, such as SCN2A and GABRG2, have also been found to cause GEFS+.
There are several different types of seizures that can occur in individuals with GEFS+. These include febrile seizures, which are seizures that are triggered by a fever; generalized seizures, which involve both sides of the brain and can cause loss of consciousness; and myoclonic seizures, which are characterized by brief, jerking movements of the muscles.
The inheritance pattern of GEFS+ can vary depending on the specific gene mutation involved. Some mutations are inherited in an autosomal dominant manner, which means that an affected individual has a 50% chance of passing the mutation on to each of their children. Other mutations can occur sporadically, meaning that they are not inherited from a parent and instead arise for the first time in an individual.
In addition to genetic testing, a diagnosis of GEFS+ can be made based on a patient’s clinical history and the specific types of seizures they experience. Genetic testing can be performed to confirm the diagnosis and identify the specific gene mutation responsible. This information can be useful in providing additional information about the condition and in guiding treatment decisions.
Researchers continue to study the causes of GEFS+ in order to better understand the underlying mechanisms of the condition and to develop more effective treatments. Several research articles and scientific resources are available that provide more information about the genes and ion channels involved in GEFS+, as well as advocacy and patient support resources.
Learn more about the genes associated with Genetic epilepsy with febrile seizures plus
Genetic epilepsy with febrile seizures plus (GEFS+) is a spectrum of epileptic disorders characterized by a combination of febrile seizures and various forms of epilepsy. This condition can be caused by mutations in various genes, each of which contributes to the development of the disorder.
One of the genes associated with GEFS+ is called GABRG2. This gene encodes a subunit of a channel protein called the GABA-A receptor. Mutations in GABRG2 can lead to alterations in the function of this receptor, resulting in abnormal excitability of neurons and an increased susceptibility to seizures.
Researchers have also identified other genes, such as SCN1A, SCN1B, and SCN2A, that are associated with GEFS+. These genes encode subunits of sodium channels, which are important for the normal functioning of neurons. Mutations in these genes can disrupt the function of sodium channels, leading to an increased risk of seizures.
Understanding the genetic basis of GEFS+ is important for several reasons. Firstly, it helps researchers and healthcare providers better understand the causes and mechanisms of the condition. This knowledge can then be used to develop targeted treatments and interventions. Additionally, genetic testing can be used to diagnose individuals with suspected GEFS+ and provide them with appropriate medical care.
Advocacy and support organizations, such as the Dravet Syndrome Foundation and the Epilepsy Foundation, provide valuable resources and information for individuals and families affected by GEFS+. These organizations offer support, education, and access to specialized medical care for individuals with the condition.
To learn more about the genes associated with GEFS+, you can refer to scientific databases and catalogs such as OMIM (Online Mendelian Inheritance in Man) and the Genetic Epilepsy Study Center at University of California, San Francisco. These resources provide detailed information about each gene and the specific variants that are associated with GEFS+.
In conclusion, Genetic epilepsy with febrile seizures plus is a complex condition associated with mutations in multiple genes. Understanding the genetic basis of this condition is crucial for improved diagnosis, treatment, and support for affected individuals and their families.
Inheritance
Genetic epilepsy with febrile seizures plus (GEFS+) is a rare and complex spectrum of epilepsy disorders characterized by a variety of seizure types, including febrile seizures and more severe forms such as generalized or partial seizures. Inheritance patterns of GEFS+ suggest that genetic factors play a major role in the development of the condition.
The majority of patients with GEFS+ have a family history of seizures, with affected individuals often having multiple affected family members. However, in some cases, the condition can occur sporadically without a family history of seizures. This suggests that both genetic and non-genetic factors may contribute to the development of GEFS+.
Researchers have identified several genes associated with GEFS+, including the GABRG2 gene, which codes for a subunit of the GABA-A receptor, a protein involved in regulating the function of inhibitory neurotransmission in the brain. Variants in the GABRG2 gene have been found in some patients with GEFS+ as well as other epilepsy-related disorders.
While variants in the GABRG2 gene are a known cause of GEFS+, the exact inheritance pattern of the condition can vary. Some cases are inherited in an autosomal dominant manner, meaning that a mutation in one copy of the gene is sufficient to cause the condition. In other cases, the inheritance pattern is more complex and may involve multiple genes or somatic mosaicism, where only some cells in the body carry the genetic mutation.
In addition to the GABRG2 gene, other genes associated with GEFS+ have also been identified, including SCN1A, SCN2A, SCN1B, and GABRD. These genes code for ion channel subunits and play a role in regulating the excitability of neurons in the brain. Variants in these genes have been found in patients with GEFS+ and related epilepsy disorders.
Genetic testing can be helpful in diagnosing GEFS+ and identifying the underlying genetic cause. Testing can be done using various methods, including targeted gene panel testing or more comprehensive sequencing approaches such as whole exome sequencing. Identification of a pathogenic variant can provide important information for treatment and management of the condition.
For additional information about inheritance and genetic testing for GEFS+, resources such as the Online Mendelian Inheritance in Man (OMIM) catalog, PubMed articles, and the Epilepsy Genetics Program at the University of California, San Francisco can be valuable sources of information. Patient advocacy and support organizations can also provide support and resources for patients and families affected by GEFS+.
Other Names for This Condition
Genetic epilepsy with febrile seizures plus (GEFS+) is also known by the following names:
- GEFS+
- Febrile seizure plus
- Epilepsy with generalized tonic-clonic seizures plus
- Epilepsy with generalized tonic-clonic seizures plus type 1
- Epilepsy with generalized tonic-clonic seizures plus type 2
- Epilepsy with generalized tonic-clonic seizures plus type 3
The condition, referred to as GEFS+, is a rare spectrum of epilepsies caused by mutations in various genes encoding ion channel subunits. The most common gene associated with GEFS+ is the SCN1A gene, which is also associated with Dravet syndrome. However, mutations in other genes such as SCN1B, SCN9A, GABRA1, GABRG2, and more, have also been identified.
GEFS+ is characterized by a combination of febrile seizures and a range of seizure types. These seizures can include myoclonic seizures, absence seizures, and other types of generalized or partial seizures. The frequency and severity of seizures can vary widely among affected individuals, even within the same family.
Diagnosis of GEFS+ is usually based on clinical features, family history, and genetic testing. Additional testing, such as electroencephalography (EEG), may be performed to support the diagnosis. Genetic testing can identify specific variants in genes associated with GEFS+.
References to articles about GEFS+ and related conditions can be found in the OMIM (Online Mendelian Inheritance in Man) database, PubMed, and other genetic literature sources. The Epilepsy Genetics Program at the University of Michigan Health System maintains a catalog of genetic variants associated with various epilepsy syndromes, including GEFS+.
Genetic advocacy groups and research centers dedicated to epilepsy and seizure disorders, such as the Dravet Syndrome Foundation and the Center for Genetic Epilepsy at NYU Langone Health, provide support and information to patients and families affected by GEFS+ and other genetic epilepsies.
In summary, GEFS+ is a rare genetic condition characterized by a spectrum of seizure types, including febrile seizures and various generalized or partial seizures. Mutations in different ion channel genes are known to cause this condition. Diagnosis is based on clinical features, family history, and genetic testing, and treatment strategies may vary depending on the specific genetic variant and the individual’s seizure frequency and severity.
Additional Information Resources
When it comes to the rare genetic condition called Genetic Epilepsy with Febrile Seizures Plus (GEFS+), there is a wealth of resources available to help individuals and families understand and cope with the condition. Here are some additional resources that can provide further information and support:
- Genetic Testing: Genetic testing can help identify the specific gene or genes responsible for GEFS+. Testing can be done through specialized genetic testing centers or laboratories. Some commonly tested genes include SCN1A, SCN1B, GABRG2, and others.
- Scientific Literature and Articles: Researchers and scientists have published numerous articles and studies about GEFS+ and related conditions. These articles can be found in scientific journals such as PubMed and Neurosci, and they provide valuable information about the causes, symptoms, and treatment options for GEFS+.
- Patient Support Organizations: There are several support organizations and advocacy groups that focus on Genetic Epilepsy with Febrile Seizures Plus and other related genetic epilepsy syndromes. These organizations can provide support, resources, and information for individuals and families affected by the condition.
- Online Resources: There are various websites and online platforms where individuals can learn more about GEFS+ and connect with others who have the condition. These resources often include forums, chat groups, and educational materials.
- Genetic Disease Registries: Some countries have established genetic disease registries where individuals affected by GEFS+ and other rare genetic conditions can register their information. This helps researchers and scientists gather data and study the condition more effectively.
- OMIM: Online Mendelian Inheritance in Man (OMIM) is a comprehensive online catalog of human genes and genetic disorders. It contains detailed information about various genetic conditions, including GEFS+.
- Epistasis/Escayg Lab: The Epistasis/Escayg Lab at Emory University is dedicated to studying the genetic causes of epilepsy. Their research focuses on GEFS+ and related conditions, and their website provides valuable information about the condition and ongoing research initiatives.
- Genetic Epilepsy Centers: Some specialized epilepsy centers have expertise in genetic epilepsy syndromes, including GEFS+. These centers often offer comprehensive evaluation and testing services, as well as personalized treatment plans.
- Patient and Family Education: Patient and family education programs can provide individuals and families with information about the condition, its management, and available resources. These programs are often offered by hospitals, clinics, and patient advocacy organizations.
These additional resources can help individuals and families affected by Genetic Epilepsy with Febrile Seizures Plus learn more about the condition, access support, and connect with others who share similar experiences.
Genetic Testing Information
The Genetic Testing information provides valuable insights into the genetic basis of Genetic Epilepsy with Febrile Seizures Plus (GEFS+). This condition is characterized by febrile seizures which are often associated with other seizure types, such as partial, generalized, or myoclonic seizures. It is a rare genetic disorder that affects the GABRG2 gene, which codes for a subunit of the GABA(A) receptor channel.
Genetic testing plays a crucial role in diagnosing GEFS+ and identifying the specific genetic variant responsible for the condition. By analyzing the patient’s genetic material, testing can detect mutations or variants in genes associated with febrile seizures and other seizure types. In addition to GABRG2, several other genes have been implicated in GEFS+.
The frequency of febrile seizures and their associated seizure types can vary significantly among individuals with GEFS+. Some individuals may only have febrile seizures during childhood, while others may develop more severe seizure types, like Dravet syndrome, later in life. Understanding the genetic causes of these conditions is crucial for personalized patient care and treatment decisions.
Genetic testing can also provide information about the inheritance pattern of GEFS+. While the condition is mainly inherited in an autosomal dominant manner, it can also occur due to de novo mutations or somatic mosaicism. Genetic counseling can help patients and their families understand the inheritance patterns and make informed decisions.
Scientific research articles and references can provide additional information about the genetic and molecular mechanisms underlying GEFS+. Researchers are continually investigating the function of the GABA(A) receptor channel and other genes involved in the condition. Resources like PubMed, the Genetic and Rare Diseases Information Center, and advocacy organizations like the Dravet Syndrome Foundation can support patients and their families in learning more about GEFS+ and finding additional sources of information and support.
| No. | Title | Authors | Journal | Year | PubMed |
|---|---|---|---|---|---|
| 1 | Genetic and molecular mechanisms underlying epilepsy. | Escayg A. | Neurosci Lett. | 2020 | PubMed |
| 2 | GABRG2 | Goldin AL. | GeneReviews | 2020 | GeneReviews |
| 3 | Epilepsy-associated variants in GABRG2 alter γ2-subunit trafficking and enhance NMDA receptor-mediated synaptic transmission. | Conroy J, et al. | Epilepsia. | 2014 | PubMed |
Genetic and Rare Diseases Information Center
Genetic epilepsy with febrile seizures plus (GEFS+) is a rare genetic condition characterized by a spectrum of seizure types, ranging from febrile seizures to more severe forms of epilepsy. This condition is caused by variants in several genes that encode different subunits of voltage-gated sodium channels.
One of the most common genes associated with GEFS+ is SCN1A, which encodes the alpha subunit of the sodium channel. Variants in SCN1A are also the cause of Dravet syndrome, another rare genetic epilepsy. Additional genes, such as SCN2A, SCN9A, and GABRG2, have been associated with GEFS+ as well.
Researchers have identified several different variants in these genes that are associated with GEFS+. These variants can affect the function of the sodium channels, leading to abnormal neuronal excitability and an increased susceptibility to seizures.
Febrile seizures are usually the first type of seizure experienced by individuals with GEFS+, and they typically occur in response to fever during childhood. However, as individuals with GEFS+ age, they may develop other types of seizures, including generalized tonic-clonic seizures, myoclonic seizures, and partial seizures.
The Genetic and Rare Diseases Information Center (GARD), an advocacy program of the National Center for Advancing Translational Sciences (NCATS), provides information about GEFS+ and other rare diseases. GARD offers a comprehensive catalog of rare disease information, including genetic and clinical summaries, articles from PubMed, and information on the names and frequency of specific gene variants associated with the condition.
For more scientific information on GEFS+ and related conditions, researchers can consult the OMIM database and PubMed articles, which contain a wealth of information on the genetics, inheritance patterns, and clinical features of these rare diseases.
It is important for patients and their families to learn about GEFS+ and other rare diseases to better understand their condition and seek appropriate medical care. Support groups and advocacy organizations, such as the Dravet Syndrome Foundation and the Epilepsy Foundation, can also provide valuable resources and support for individuals with GEFS+ and their families.
| Gene | Associated Condition |
|---|---|
| SCN1A | Genetic epilepsy with febrile seizures plus (GEFS+), Dravet syndrome |
| SCN2A | Genetic epilepsy with febrile seizures plus (GEFS+) |
| SCN9A | Genetic epilepsy with febrile seizures plus (GEFS+) |
| GABRG2 | Genetic epilepsy with febrile seizures plus (GEFS+) |
Individuals with GEFS+ should work closely with their healthcare team to develop an appropriate treatment plan that may include antiepileptic medications, lifestyle modifications, and seizure management strategies.
Patient Support and Advocacy Resources
For patients and their families affected by Genetic Epilepsy with Febrile Seizures Plus (GEFS+), there are several resources available to provide support and advocacy. These resources offer information about the condition, its causes and inheritance, as well as additional support for patients and their families.
- Epilepsy Foundation – The Epilepsy Foundation is a common resource for individuals and families living with epilepsy. They offer educational resources, support groups, and advocacy services for individuals with various types of epilepsy, including GEFS+.
- Genetic and Rare Diseases Information Center (GARD) – GARD is a program of the National Center for Advancing Translational Sciences (NCATS) and provides information and resources on rare genetic diseases, including GEFS+. They offer fact sheets and other educational materials, as well as a toll-free helpline for personalized support and guidance.
- GEFS+ Research and Support Network – This network aims to connect individuals and families affected by GEFS+ with each other and with researchers studying the condition. They provide a platform for sharing experiences, accessing up-to-date scientific information, and participating in research opportunities.
Additionally, there are several scientific articles and publications available on PubMed and other research databases that provide more information about GEFS+ and related conditions. These articles often discuss the genetic variants and genes associated with the condition, as well as the underlying mechanisms and pathophysiology.
Some key references include:
- Escayg, A., Goldin, A. L., & Seavayg, A. (2000). The genetic basis of human epilepsy. Trends in Neurosciences, 23(11), 541-546.
- Escayg, A., & Meisler, M. H. (2001). Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects. Journal of Physiology, 534(3), 691-697.
- Catalog of Genes and Diseases (CGD). (2004). GEFS+ (Genetic Epilepsy with Febrile Seizures Plus). Retrieved from http://www.cgd.pt
These resources, both for support and informational purposes, can help individuals and families navigate the challenges associated with GEFS+ and find the necessary resources and support they need for managing the condition.
Catalog of Genes and Diseases from OMIM
The OMIM (Online Mendelian Inheritance in Man) database provides a comprehensive catalog of genes and diseases. One of the genetic conditions included in this catalog is Genetic Epilepsy with Febrile Seizures Plus (GEFS+).
GEFS+ is a rare genetic epilepsy syndrome characterized by a spectrum of seizure types, ranging from febrile seizures to more severe forms such as Dravet syndrome. The condition is associated with mutations in the GABRG2 gene, which codes for the GABA(A) receptor subunit gamma-2 protein.
The GABRG2 gene is involved in the function of GABA(A) receptors, which are critical for inhibitory neurotransmission in the brain. Mutations in this gene can lead to altered GABA(A) receptor function, resulting in abnormal neuronal excitability and seizures.
Patients with GEFS+ usually have a history of febrile seizures, which are characterized by seizures that occur during fever episodes in childhood. These febrile seizures can progress to more severe forms of epilepsy, including generalized seizures and myoclonic seizures.
Genetic testing can be performed to identify mutations in the GABRG2 gene, providing a definitive diagnosis for patients with GEFS+. However, it is important to note that not all individuals with GEFS+ will have mutations in this gene, indicating the involvement of other genes in the condition.
Additional genes associated with GEFS+ and related epileptic conditions have also been identified, such as SCN1A and SCN9A, which code for sodium channels involved in neuronal excitability. Somatic variants in these genes can contribute to the development of epilepsy.
For more information about GEFS+ and other related genetic epilepsies, the OMIM database provides scientific articles, references, and citations. These resources can be used to learn more about the genetic basis of these conditions and support advocacy efforts for patients and their families.
In summary, the OMIM database serves as a valuable catalog of genes and diseases, providing information about genetic variants associated with epilepsy, including Genetic Epilepsy with Febrile Seizures Plus. The catalog includes genes such as GABRG2, SCN1A, and SCN9A, which play crucial roles in neuronal excitability and seizure development. Genetic testing and scientific research continue to uncover additional genes and variants associated with these conditions, furthering our understanding of the underlying mechanisms and opening doors for targeted therapies.
Scientific Articles on PubMed
Genetic epilepsy with febrile seizures plus (GEFS+) is a rare genetic condition characterized by febrile seizures and other types of seizures, such as myoclonic seizures and partial or generalized epilepsy. It is usually inherited in an autosomal dominant manner, meaning that one copy of the gene mutation is sufficient to cause the condition.
Several genes have been associated with GEFS+, including SCN1A, SCN1B, SCN2A, SCN9A, GABRG2, and others. These genes encode for proteins that are involved in the function of ion channels in the brain. One of the most well-known genes associated with GEFS+ is SCN1A, which is also associated with a severe form of epilepsy called Dravet syndrome.
Scientific articles on PubMed provide valuable information about the genetic variants and their functional implications in GEFS+. Researchers have been able to identify specific mutations in these genes and study their effects on ion channel function.
One such study by Escayg et al. (2000) identified a recurrent mutation in the GABRG2 gene in a family with GEFS+. This mutation resulted in a loss of function of the GABA-A receptor, an important protein for inhibiting neuronal activity. The researchers also found that this mutation led to an increased excitability of neurons, which could contribute to the development of seizures.
Other studies have focused on the genetic basis of febrile seizures, a common feature of GEFS+. In one such study, Goldin et al. (2001) identified two mutations in the SCN1A gene that were associated with febrile seizures. These mutations resulted in altered sodium channel function and increased excitability of neurons.
Scientific articles on PubMed also provide information about the frequency of these genetic variants in the general population. For example, a study by Claes et al. (2001) found that the GABRG2 mutation identified in GEFS+ patients was present in approximately 1% of the population, making it a relatively rare variant.
In addition to providing scientific information, PubMed also serves as a valuable resource for patients, families, and advocacy organizations. It provides access to information about the genetic variants associated with GEFS+, as well as resources for genetic testing. The PubMed catalog includes citations to scientific articles, as well as information about related conditions, inheritance patterns, and available support and advocacy organizations.
Overall, the scientific articles on PubMed offer a wealth of information about the genetics, function, and causes of GEFS+ and related conditions. They provide researchers, healthcare professionals, and patients with valuable insights into the underlying mechanisms of the condition, as well as potential avenues for future research and treatment.
References
- Escayg A, Goldin AL. Sodium channel SCN1A and epilepsy: mutations and mechanisms. J Clin Invest. 2010;120(5):963-5. doi:10.1172/JCI43090
- Dravet C. The core Dravet syndrome phenotype. Epilepsia. 2011;52 Suppl 2:3-9. doi:10.1111/j.1528-1167.2011.03035.x
- OMIM Entry – #602066 – GABA-A receptor, gamma 2; GABRG2. Online Mendelian Inheritance in Man. [cited 2021 Jun 15]
- Loddenkemper T, Gavva S, Geschwind DH. The role of genetic testing in epilepsy diagnosis and management. JAMA Neurol. 2014;71(6): e1-e5. doi:10.1001/jamaneurol.2013.6508
- Kasperavičiūtė D, Catarino CB, Heinzen EL, et al. Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study. Brain. 2010;133(7):2136-2147. doi:10.1093/brain/awq130
- National Institute of Neurological Disorders and Stroke. Febrile Seizures Information Page. [cited 2021 Jun 15]
- Goldin AL. Mechanisms of sodium channel inactivation. Handb Exp Pharmacol. 2018;246:211-228. doi:10.1007/164_2017_46