Epilepsy is a brain disorder caused by an imbalance in the electrical activity of neurons in some area of the brain. For exhaustive, thorough, and detailed details of the pathology, we have another blog entry where we delve into the types of epilepsy.
Here we are going to focus on the question of the heritability of epilepsy.
Since the heritability of a characteristic is linked to its genetics, let’s delve into the genetics of this disease.
Causes of epilepsy: genetic and non-genetic
First, we must clarify that not all epilepsies have a genetic origin.
This is an important detail to emphasize. Epilepsy is not a single disease but rather encompasses many diverse conditions that meet the basic condition: sudden, short-duration events with excessive and abnormal brain activity. Therefore, within the term, we find different classifications and types of epileptic seizures.
If we ask what causes epilepsy, we must first distinguish between genetic and non-genetic causes.
In many cases, the disease is due to brain damage. The main leading causes of epilepsy are strokes, brain tumors, traumatic brain injury, drug use, brain infections, or lack of oxygen during birth.
Even if there is a genetic predisposition above average in the individual, the initial trigger can be an environmental factor. It is not uncommon for a person’s first epileptic seizure, especially in young people, to be due to substance use. Subsequently, when treated, it is discovered that they had family history of the condition and were prone to developing it.
Although lifestyle has significantly accelerated the onset, it is considered that between 30-40% of epilepsies had a previous genetic predisposition.
For the same reason, an individual with first-degree relatives who suffer from the disease has a risk of epilepsy between two and four times higher than average.
You suspect, but do not confirm the cause
There is also a type of epilepsy called idiopathic epilepsy in which the causes are unknown. It’s not that they are entirely unknown; it is assumed that they are caused by genetic alterations, but the specific anomalies responsible for the disease are not detected. Their transmission to offspring also does not follow the normal patterns of inherited diseases.
These individuals have a structurally normal brain, and most of the time, there has been no triggering event.
It has been observed that lack of sleep is an additional risk factor in these epilepsies. It appears that these patients are predisposed to seizures due to their genetics. Additionally, they tend to manifest early, during childhood and adolescence.
Fortunately, the majority of these cases respond well to treatment, and those affected do not see a decrease in their intellectual and/or cognitive abilities.
There is another special group of epilepsies, cryptogenic epilepsies. These epilepsies also have unknown causes, but unlike idiopathic ones, it has been ruled out that they are due to genetics.
In cryptogenic cases, the responsible factors would be histopathological and cellular alterations.
It is estimated that in approximately half of all people diagnosed with epilepsy worldwide, the direct cause of the disease is unknown.
So, is epilepsy hereditary or acquired?
The honest and brief answer to this question is: it depends on the type of epilepsy the patient has. Saying that epilepsy is hereditary is an inaccurate statement.
Epilepsy is a brain disorder that encompasses conditions sharing symptoms and effects on the brain, but with different underlying causes.
There are epileptic diseases with autosomal dominant inheritance. If one of the two parents has the disease, the risk of their children having it is 50%.
For example, benign familial neonatal epilepsy (BFNE) is a genetic syndrome with febrile seizures that occur in newborns. Unfortunately, in some cases, there is already epilepsy in the baby. The responsible genes are KCNQ2 and KCNQ3.
Autosomal dominant sleep-related hypermotor epilepsy (ADNFLE) is another form of epilepsy with autosomal dominant inheritance. If anyone is curious about the name, it’s because affected individuals have involuntary contractions and movements while asleep. Currently, there are 7 genes implicated in the disease.
There are also recessive forms of epilepsy, which have a worse prognosis than dominant ones.
Among them, we have Lafora disease, due to a problem in glycogen metabolism. Insoluble polyglucosan deposits form, affecting various organs including the brain, causing seizures, among other symptoms. The responsible genes are EPM2A or EPM2B.
Unverricht-Lundborg syndrome is another type of autosomal recessive epilepsy. It arises from 8-13 years old and is common in the Baltic region. In this case, it is due to the CSTB gene.
Another autosomal recessive one is pyridoxine-dependent epilepsy, due to the ALDH7A1 gene. It is one of the earliest-onset ones, with seizures in the baby. Some experts speculate that there could even be seizures before birth.
With such a broad range of diseases included in the epilepsy group, we find some linked to the patient’s sex.
The ARX gene codes for a protein involved in regulating other genes. It is necessary during embryonic development for the maturation of various organs, including the brain. The gene is located on the X chromosome, causing X-linked epilepsy.
PCDH19 epilepsy, due to the PCDH19 gene, is a curious case. The gene encodes a protein in the nervous system involved in cell communication. The gene is located on the X chromosome, but unlike the previous one, the disease primarily affects girls (as it manifests at early ages), with very few cases registered in boys.
Epilepsies due to genetic alterations, outside of specific cases, have non-Mendelian heritability. To put it colloquially, their heritability is VERY complicated.
The good news is that the risk of developing the disease due to having relatives with it is much lower than other genetic diseases. The bad news is that predicting the risk is also more complicated. The first step is to categorize which specific epilepsy, within the repertoire of options, the patient has.
If epilepsy is not genetic, it cannot be inherited. If an epileptic patient has developed the disease from encephalitis, their children do not have a higher risk than average of developing the disease.
In summary, epilepsies encompass brain disorders that may or may not be hereditary; some are, and the hereditary ones present all forms of heritability that may exist.
In these cases, a genetic test like tellmeGen’s Advanced DNA Kit can shed some light.
