Epilepsy - is it hereditary?

Epilepsy is a condition that can affect anyone - at any age, regardless of lifestyle. According to statistics, only every second patient has a chance to learn the cause behind this disorder. Is heredity one of them? The answer to this question is not straightforward, and specialists prefer to speak of genetic "conditioning" or "background".

Table of Contents

• Epilepsy - a Multifactorial Disease
• Genetically Determined Epilepsy: Mono- or Polygenic
• What Tests Can Help in Diagnosing Epilepsy?
• Intensive Research

Epilepsy - a Multifactorial Disease

Experts have established a connection between epileptic seizures and genetic factors. However, it should be noted that epilepsy belongs to multifactorial diseases whose familial occurrence happens but is not frequent.

Certain types of epilepsies or epileptic syndromes can be classical genetic diseases. The first scientific evidence of gene mutations leading to epilepsy development appeared in 1995. A gene was discovered then whose mutation was responsible for the faulty function of GABA receptors (these influence proper nervous system functioning) and consequently for partial epileptic seizures that affect one brain area.

Currently, it is believed that nearly half of all epilepsy cases have a genetic basis. This means that specific mutations occur in genes whose proteins perform particular functions in nerve cells. Their detection and recognition that a given epilepsy case has a genetic basis allows for identifying similarities to genetic causes of other neurodevelopmental disorders such as autism or intellectual disability.

It's worth emphasizing that in epileptology, there is a view that the earlier epilepsy is diagnosed, the more likely its cause is genetic. This type of epilepsy can manifest even on the first day of life.

Genetically Determined Epilepsy: Mono- or Polygenic

The basic division of genetically determined epilepsies assumes the following distinction:

• Monogenic epilepsies - major defect, i.e., mutation in one gene
• Polygenic epilepsies - minor defects in multiple genes

In some cases, specialists can identify which type they're dealing with.

Polygenic (multifactorial) epilepsy typically manifests later in life, usually as focal seizures affecting one part of the brain. They are also often caused by a single developmental defect of the nervous system. More often, however, the disease basis is much more complex.

Monogenic epilepsy is most often suspected in cases of epileptic encephalopathy - situations where epilepsy is accompanied by other developmental disorders, such as intellectual disability or developmental delays. Parents or caregivers may then observe additional developmental regression in their child caused by epileptic seizures. In epileptic encephalopathies, seizures appear already in early infancy or the neonatal period.

Moreover, monogenic epilepsy is also suspected in cases of epileptic syndromes like Dravet or West syndrome. Specialists particularly consider it when generalized seizures occur, characterized by epileptic discharges in both hemispheres simultaneously.

What Tests Can Help in Diagnosing Epilepsy?

Currently, genetically determined epilepsy can be identified in several dozen percent of examined patients. This is a major change, as 10-15 years ago, this detectability was only a few percent. Diagnostic tests include:

• WES examination* - innovative test allowing assessment of all coding sequences in each gene
• Microarray testing - (CGH or aCGH) test excluding or confirming chromosomal rather than monogenic disease basis
• Metabolic tests - examination ordered when congenital metabolic defects are suspected

Intensive Research

Currently, worldwide research is being conducted on the genetic basis of epilepsy. In Poland, this includes the "EPIMARKER" program in Poznań and "EPISTOP" at Warsaw Medical University. Outside our country, the significant British "Epilepsy Genomics" project focuses on epileptic syndromes.

European Reference Networks also play a major role in deepening knowledge about epilepsy inheritance. One of its elements is the "EPICARE" initiative gathering clinics dealing with epilepsy treatment and diagnostics.

*Examination available at Neurosphera. Learn more about its course, indications for its performance, and benefits of knowing the results.

Scientific collaboration: Dr. hab. med. Krzysztof Szczałuba.