Is Epilepsy Hereditary? It is estimated that 1 in 26 people will develop epilepsy in their lifetime. While the cause of epilepsy is unknown in the majority of cases, researchers have identified certain genes that may be associated with the disorder. In this article, we will discuss what is known about the genetics of epilepsy and whether there is a single “epilepsy gene.”
Xcode Life's Genetic Epilepsy DNA Report
Researchers have identified several genes associated with epilepsy.
In the sample report below, we've attempted to analyze some important genes that increase the risk of epilepsy.
You can identify your genetic risk of epilepsy by using your 23andMe DNA data and placing an order for the Gene Health Report.
Epilepsy: An Overview
Epilepsy is a chronic neurological disorder that affects people of all ages.
It is characterized by recurrent seizures ranging from brief and nearly undetectable to long and debilitating.
Epilepsy can be caused by many factors, including head injuries, genetic predisposition, and infections.
There is no cure for epilepsy, but certain medications and treatments can help manage it effectively.
What Is Genetic Epilepsy?
Epilepsy is genetic if the seizures occur due to a genetic defect.
However, not all cases of genetic epilepsy are inherited.
Some genetic defects can occur spontaneously in people even if they are not present in either biological parent.
Most cases of idiopathic (cause unknown) epilepsy are due to abnormal changes in several genes.
Each of these genes contributes to a small percentage of epilepsy risk; when someone inherits a combination of these genes, they can be at high risk for epilepsy.
Is Epilepsy Hereditary?
Genetic variants underlie about 30-40% of epilepsy cases.
- If either of the biological parents has epilepsy, there’s a 2-12% chance that their child will too.
- Epilepsy risk increased by 2-4 fold for people with epilepsy history in their first-degree relatives.
- Siblings of children with epilepsy are at an increased risk of developing it.
- Children with a biological mother who has epilepsy are at higher risk than those with a biological father who has epilepsy.
However, analyzing a person’s chance of inheriting epilepsy is complicated.
For instance, two siblings with epilepsy may have inherited mutations in different genes.
On the other hand, two family members with the same genetic mutation for epilepsy may manifest symptoms in different ways.
Furthermore, inheritance pattern varies depending on the type of epilepsy - like focal, idiopathic, or generalized epilepsy.
What are the chances of your inheriting epilepsy?
- If only the biological mother has epilepsy, the chances of inheriting it are <5%.
- If only the biological father has epilepsy, the risk is slightly lesser.
- If both biological parents have epilepsy, then the risk is higher.
- If one of the biological parents has idiopathic epilepsy, the risk can be as high as 12%!
Genes Associated with Epilepsy
With the advancements in genetic technologies, research studies are discovering more and more genes associated with epilepsy.
According to a study based on search results from the OMIM database, 84 genes were classified as epilepsy genes.
Some are directly associated with epilepsy, some are associated with conditions whose core symptom is epilepsy, and some are associated with epilepsy and multiple other phenotypes.
Summary of the epilepsy genes classified according to phenotype and age - as taken from Science Direct.
| Phenotype (in order of the onset age) | Gene |
| Neonatal | |
| Pyridoxamine 5'-phosphate oxidase deficiency (PNPOD) | PNPO |
| Pyridoxine-dependent epilepsy (EPD) | ALDH7A1 |
| Benign familial neonatal seizures (BFNS) | KCNQ2, KCNQ3 |
| Infantile and childhood | |
| Familial infantile myoclonic epilepsy (FIME) | TBC1D24 |
| Benign familial infantile seizures (BFIS) | PRRT2, SCN2A, SCN8A |
| Amish infantile epilepsy syndrome (AIES) | ST3GAL5 |
| Early infantile epileptic encephalopathy (EIEE) | CACNA1A, GABRA1, GABRB3, KCNQ2, KCNT1, SCN2A, SCN8A |
| AARS, ARV1, DOCK7, FRRS1L, GUF1, ITPA, NECAP1, PLCB1, SLC12A5, SLC13A5, SLC25A12, SLC25A22, ST3GAL3, SZT2, TBC1D24, WWOX | |
| CDKL5 | |
| ARHGEF9 | |
| ALG13, PCDH19 | |
| DNM1, EEF1A2, FGF12, GABRB1, GNAO1, GRIN2B, GRIN2D, HCN1, KCNA2, KCNB1, SIK1, SLC1A2, SPTAN1, STXBP1, UBA5 | |
| Dravet syndrome (DS) | SCN1A, SCN9A |
| Familial febrile seizures (FFS) | GABRG2, GPR98, SCN1A, SCN9A |
| CPA6 | |
| Generalized epilepsy with febrile seizures plus (GEFS + ) | GABRD, GABRG2, SCN1A, SCN1B, SCN9A, STX1B |
| Generalized epilepsy and paroxysmal dyskinesia (GEPD) | KCNMA1 |
| Myoclonic-atonic epilepsy (MAE) | SLC6A1 |
| Childhood-onset epileptic encephalopathy (COEE) | CHD2 |
| Focal epilepsy and speech disorder (FESD) with or without mental retardation | GRIN2A |
| Childhood absence epilepsy (CAE) | GABRG2 |
| CACNA1H, GABRA1, GABRB3 | |
| Juvenile and later | |
| Juvenile absence epilepsy (JAE) | CLCN2, EFHC1 |
| Juvenile myoclonic epilepsy (JME) | CACNB4, CLCN2, EFHC1, GABRD |
| GABRA1 | |
| Idiopathic generalized epilepsy (IGE) | CACNB4, CLCN2, GABRD, SLC12A5, SLC2A1 |
| CACNA1H, CASR | |
| Familial adult myoclonic epilepsy (FAME) | ADRA2B |
| CNTN2 | |
| Familial temporal lobe epilepsy (FTLE) | CPA6, GAL, LGI1 |
| Not specific | |
| Progressive myoclonic epilepsy (PME) | KCNC1 |
| CERS1, CSTB, EPM2A, GOSR2, KCTD7, LMNB2, NHLRC1, PRDM8, PRICKLE1, SCARB2 | |
| Nocturnal frontal lobe epilepsy (NFLE) | CHRNA2, CHRNA4, KCNT1 |
| CHRNB2 | |
| Familial focal epilepsy with variable foci (FFEVF) | DEPDC5 |
Other Causes of Epilepsy
- Trauma to the head: In some people, traumatic head injuries due to a car accident or other incidents can result in epilepsy.
- Certain neurological conditions: Some conditions like brain tumors, stroke, or vascular malformation can result in brain damage, ultimately leading to epilepsy. In fact, brain damage due to stroke is one of the leading causes of epilepsy.
- Brain damage to the fetus during pregnancy: Poor nutrition during pregnancy, oxygen deficiency, or certain infections can result in brain damage to the fetus.
- Infectious diseases: Some infections associated with epilepsy include neurocysticercosis, cerebral malaria, TORCH infections, bacterial meningitis, viral encephalitis, tuberculosis, and human immunodeficiency virus (HIV).
Common Epilepsy Triggers
Epilepsy trigger is not the same as epilepsy cause.
Triggers are discussed in a person who already has epilepsy.
Triggers result in seizures in a person with epilepsy.
Some common triggers are:
- Sleep deprivation
- Alcohol consumption/withdrawal
- Fever
- Hypoglycemia (low blood sugar)
- Stress
- Dehydration
- Toxin exposure
- Hormonal changes accompanying the menstrual cycle
- Certain medications
Types of Genetic Testing For Epilepsy
Karyotyping
Used to identify any changes in the number of chromosomes and large deletions, duplications, and inversions of the genetic material.
Chromosomal Microarray (CMA)
A very common choice for epilepsy genetic tests.
Around 10% of people with epilepsy have abnormal CMA results.
Used to visualize missing or extra pieces of genetic material.
Gene Panels
Uses next-generation sequencing (NGS) technologies to visualize multiple genes associated with epilepsy simultaneously.
Whole-exome Sequencing (WES)
Analyzes all the portions of the DNA that make protein.
Can explain the genetic cause of 30% of epilepsy cases.
Whole-genome Sequencing
Analyze the entire DNA content (the genome) of an individual.
Currently employed majorly for research purposes and not so much in clinical settings.
Genotyping
Analyzes genetic changes called single nucleotide polymorphisms associated with epilepsy.
Not used for diagnosis; provide a genetic risk landscape for epilepsy.
Do You Have A Genetic Risk For Epilepsy? Find Out With The Gene Health Report.
Summary: Is Epilepsy Hereditary?
Epilepsy is a neurological condition characterized by recurrent seizures.
Most idiopathic epilepsy cases have a genetic background do it.
Epilepsy in biological parents increases the risk of their children developing it; the risk increases when the biological mother is affected.
Most genes implicated in epilepsy play a role in regulating the entry of ions like sodium and calcium into the cell.
Some diagnostic genetic tests for epilepsy include karyotyping, chromosomal microarray, and whole-exome and whole-genome sequencing.
Genotyping analyzes small changes in genes (called single nucleotide polymorphisms) to provide a genetic risk landscape for epilepsy.
