Epilepsy is one of the most common neurologic disorders that affect around 4% of individuals at some point in their lives. There have been researched when it comes to its relationship with genetics. However, little progress has been made in understanding the genetic influence on the disease. The etiology of the development of Epilepsy is complicated and is not completely understood. However, a wide variety of people having Epilepsy don’t have a history of family Epilepsy. Some epilepsies run in families and are passed down from one to the other generation. These epilepsies are both inherited and genetic. As far as Epilepsy is concerned, advancements in technology and analytics have led to remarkable progress in gene discovery. The first Epilepsy-related genes were identified in the late 1990s, and the advancement in DNA sequences have helped identify hundreds of gene playing a significant role in Epilepsy. Some of the genes are identified to be specific to Epilepsy. Other genes are usually responsible for delays like development delay, autism spectrum disorder, and intellectual disability.
The past 20 years and genetic influence on Epilepsy
A lot of genetic studies have been conducted involving isolated multigenerational families with monogenic diseases or genome-wide association studies. The single nucleotide polymorphisms were used to find the loci associated with the disease. The results concluded that not just a single gene can be responsible for epilepsies. DNA sequencing techniques are used to detect de novo mutation as they’re not inherited from Parents. Accurate prognostic information can be achieved from a genetic diagnosis depending on the mutation found.
Researches on the role of genetics in Epilepsy
Many medical centers all around the world are undertaking research to understand the influence and role of genetics in the development of Epilepsy. The research is aimed at precision medicine. This will lead to the treatment of patients with Epilepsy using the specific approaches in accordance with genetic diagnosis conducted. Three types of studies are mainly involved in the field of Epilepsy genetics:
- Natural History studies
- Clinical Trials
- Functional Studies
Despite a lot of advancements in anti-epileptic medications, the clinical management of Epilepsy is complex, and it’s not easy to maintain the symptoms. Many drugs being used for the treatment of Epilepsy are having serious side effects. It is a major health problem that needs identification of its underlying cause in order to develop new treatments that are effective. This complex disorder has a highly variable phenotype. Let’s take a look at the two natures:
The paroxysmal nature of this disease involves seizures that look completely spontaneous or are triggered by different environmental factors like drugs or stress.
The heterogeneous nature of the seizure phenotypes appears with different behavioral patterns even among people of a single-family. Studies found that there is a particular genetic component involved in the development of Epilepsy.
So, genetic studies of human Epilepsy focus on rare phenotypes in isolated families where the disease is inherited in a way that is predicted depending on the laws of Mendel. Also, a number of Epilepsy causing gene mutations are discovered. These discoveries have been helpful in providing information related to the general biology of seizures. Whereas, there are just a few studies focusing on the common Epilepsy types that result from the effects of many genetic variants.
Genetic influences contribute to the Epilepsy phenotypes in both animals and humans. The genetic linkage data is collected through the use of typical family and twin study designs. A lot of Epilepsy forms have complex patterns of inheritance due to gene variation and their interaction with environmental factors. So, here are some of the highlights when it comes to the relationship between genetics and Epilepsy:
- Genetic disorders can be the only cause of Epilepsy or can result in a disease like Epilepsy with a number of effects on the organs and functionality of one’s body
- It can be found in a person directly or indirectly from the genetic disorders linked to a particular gene or a combination of both genetic and environmental factors, mutations in DNA, or any missing or mutated chromosomes.
- If there are mutations in genes, chances are, a person will get Epilepsy
- Family studies have concluded that some Epilepsy syndromes are determined by genetics
- If a parent has idiopathic Epilepsy, there is a 9%-12% chance that the child will have Epilepsy too
- If a child in the family has Epilepsy, chances are, his/her siblings will get the disease too.
- Women with Epilepsy have a higher chance of transferring it to their children as compared to men
Epilepsy syndromes linked to genetic disorders
The inheritance of Epilepsy is complex. For instance, two children with mutations on different genes may develop having the same Epilepsy syndrome. Similarly, two members of a family with the same gene mutation may both get Epilepsy, but both can have different effects. So, it can be said that some of the Epilepsy syndromes can be caused by genes, but the genes responsible for that have not been identified.
Single Gene Disorders
As of now, 20 syndromes with Epilepsy as their main feature have been linked to specific genes and most of the single-gene disorders causing brain disorders can have Epilepsy as a symptom. Let’s take a look at these major single-gene Epilepsy syndromes:
- Autosomal dominant partial Epilepsy with variable foci
- Autosomal dominant nocturnal frontal lobe Epilepsy
- Benign familial neonatal convulsions
- Benign infantile familial convulsions
- Familial temporal lobe Epilepsy
- Generalized Epilepsy with febrile seizures plus
- Progressive myoclonus epilepsies
Multifactorial Gene Disorders
Some Epilepsy syndromes that are thought to be multifactorial or complex such that they are affected by both genes and environmental factors:
- Myoclonic astatic Epilepsy
- Benign Epilepsy of Childhood with Centrotemporal spikes
- Benign Myoclonic Epilepsy of Infancy
- Benign myoclonic Epilepsy of infancy
- Juvenile Myoclonic Epilepsy
- Childhood absence Epilepsy
- Juvenile Absence Epilepsy
Multifactorial Gene Disorders
Mitochondrial disorders occur when the mitochondria fail and don’t produce the energy a cell or tissue needs. Myoclonus Epilepsy and ragged-red is progressive myoclonus Epilepsy caused due to the mutation in mitochondrial DNA.
Chromosomal mutations ring chromosomal abnormalities and include:
- Down Syndrome
- Other trisomies
- Wolf Hirchhorn Syndrome
- Angelman Syndrome
- Ring Chromosome abnormalities