Genetic Testing and Epilepsy
When genes can help explain why seizures happen
Epilepsy can have many causes.
For some people, seizures develop because of a structural brain abnormality, previous injury, stroke, infection, immune condition or another identifiable cause.
For others, genetic changes contribute to why the brain is susceptible to seizures.
Genetic testing can sometimes identify that cause.
A genetic result may help doctors:
identify a particular epilepsy syndrome
understand why epilepsy developed
choose or avoid particular treatments
recognise other health problems that may need monitoring
provide information about likely future development
and give families more accurate information about inheritance.
But genetic testing does not provide an answer for everyone.
A negative test does not prove that someone's epilepsy has no genetic component. Our understanding of epilepsy genetics is still developing.
What are genes?
Genes are sections of DNA containing instructions used by the body to develop and function.
Humans have thousands of genes.
Different genes influence:
how brain cells develop
how neurons communicate
ion channels
neurotransmitters
metabolism
brain structure
and many other biological processes.
Most differences in DNA are harmless.
But occasionally a change in a particular gene interferes with an important biological process enough to cause or contribute to disease.
These changes are usually called genetic variants.
Older information may use the word mutation, but variant is now commonly preferred.
Is all epilepsy genetic?
No.
Epilepsy is a very broad group of conditions.
Some epilepsies have a strong identifiable genetic cause.
Others probably result from a combination of many genetic differences together with environmental or biological factors.
Others have a recognised non-genetic cause.
And for many people, the cause remains unknown.
Approximately knowing that epilepsy is “genetic” is therefore not enough.
The important question is:
What kind of genetic contribution is involved?
Genetic does not mean inherited
This is one of the most important distinctions.
A condition can be genetic without having been inherited from either parent.
Some disease-causing variants arise for the first time:
in an egg
in a sperm
or very early after conception.
These are known as de novo variants.
A child can therefore have a genetic epilepsy even when:
neither parent has epilepsy
no sibling has epilepsy
and there is no known family history at all.
Epilepsy Action specifically notes that genetic variants can be inherited or can arise for the first time in an individual.
What does inherited mean?
An inherited variant has been passed from a biological parent to their child.
Different conditions follow different inheritance patterns.
These can include:
Autosomal dominant inheritance — one altered copy of a gene may be sufficient to increase the chance of the condition.
Autosomal recessive inheritance — disease usually occurs when altered copies are inherited from both parents.
X-linked inheritance — the relevant gene is located on the X chromosome.
Mitochondrial inheritance — variants in mitochondrial DNA are generally inherited through the biological mother.
Genetics can become much more complicated than these simplified patterns.
That is one reason genetic counselling can be valuable.
Having the variant does not always mean having epilepsy
Some disease-associated genetic variants show reduced penetrance.
This means a person may carry a relevant variant without developing epilepsy.
Another concept is variable expression.
Members of the same family carrying the same genetic change may experience very different effects.
For example, one family member might have:
febrile seizures in childhood
while another has:
lifelong epilepsy
and another may have:
no seizures at all.
This is why genetics does not always provide a simple prediction of exactly what will happen to an individual.
Some epilepsies involve one major gene
A condition largely caused by a disease-causing change in a single gene is sometimes described as monogenic.
Examples of genes associated with particular genetic epilepsies include:
SCN1A, commonly associated with Dravet syndrome and some related epilepsies.
PRRT2, which can be associated with self-limited infantile epilepsy and certain movement disorders.
Many other genes are associated with developmental and epileptic encephalopathies and other epilepsy syndromes.
There is no single “epilepsy gene”.
Hundreds of genes are now known to be associated with epilepsy, and knowledge continues to expand.
Other epilepsies are genetically complex
Not every genetic epilepsy has one identifiable disease-causing variant.
The genetic generalised epilepsies, for example, include:
childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy and epilepsy with generalised tonic-clonic seizures alone.
These conditions have a genetic basis, but in many people there is no single causative variant that can be identified through routine clinical testing.
Several genetic factors may combine to influence seizure susceptibility.
So someone can legitimately be diagnosed with a genetic generalised epilepsy without having a genetic-test report naming one particular gene.
Who should be considered for genetic testing?
Genetic testing is not currently recommended routinely for every person with epilepsy.
NICE recommends considering whole-genome sequencing for people whose epilepsy has no known cause and who meet particular features.
These include epilepsy that:
began before the age of 2
has features suggesting a particular genetic epilepsy syndrome, such as Dravet syndrome
occurs alongside learning disability
occurs alongside autism
occurs with particular structural or developmental abnormalities
or is associated with otherwise unexplained cognitive or memory decline.
Testing may also be considered for epilepsy beginning between ages 2 and 3 when a specialist multidisciplinary team agrees it is appropriate.
The criteria do not mean that genetic epilepsy only occurs in young children.
They identify groups in whom current testing is particularly likely to provide clinically useful information.
Why is early-onset epilepsy particularly important?
When seizures begin during infancy, there is a greater chance that a single important genetic or metabolic cause may be involved.
Finding the cause early can sometimes affect:
treatment
developmental assessment
monitoring
counselling
and investigation of other organs or systems.
This is why NICE gives particular emphasis to epilepsy beginning before 2 years of age.
Adults can have genetic epilepsy too
Genetic testing is sometimes mistakenly thought of as something only children have.
Adults may have:
an epilepsy that began in childhood but was never genetically investigated
intellectual or developmental difficulties alongside epilepsy
a strong family history
an unusual epilepsy syndrome
unexplained cognitive decline
or another pattern that raises suspicion of a genetic condition.
Whether testing would be useful depends on the individual clinical situation and current NHS eligibility criteria.
How is genetic testing arranged?
In the NHS, an epilepsy specialist, neurologist or genetics service may discuss whether testing is appropriate.
NICE recommends discussing uncertainty about genetic testing with a neurologist or geneticist and using the NHS National Genomic Test Directory when deciding which test is appropriate.
In England, the National Genomic Test Directory lists:
which genomic tests are funded
who is eligible
which specialists can request them
and which testing approach should be used.
The directory is regularly updated as genomic knowledge changes. The current rare-disease directory was updated during 2026.
What sample is needed?
Testing commonly uses:
blood
or sometimes saliva.
The sample contains DNA that can be analysed in a genomic laboratory.
The person does not normally need to stop epilepsy medication for genetic testing.
The test is looking at DNA rather than trying to provoke or record a seizure.
What is a single-gene test?
If doctors have a very strong suspicion that one particular gene is responsible, testing can be focused on that gene.
For example, a specific clinical syndrome may make one gene particularly important.
However, epilepsy genetics often overlaps between genes.
The same syndrome can sometimes result from variants in several different genes, while variants in one gene can sometimes cause several different clinical presentations.
For that reason, broader genomic testing is now often more useful than testing genes one by one.
What is a gene panel?
A gene panel analyses a selected group of genes known to be associated with a particular clinical problem.
An epilepsy panel might include many genes associated with:
seizures
developmental epileptic encephalopathies
ion-channel disorders
metabolic epilepsies
and recognised epilepsy syndromes.
The exact genes included can change as scientific knowledge improves.
What is whole-exome sequencing?
The exome consists of the protein-coding parts of genes.
Although these regions make up only a relatively small proportion of the genome, many known disease-causing variants are found there.
Whole-exome sequencing therefore analyses coding regions across many genes simultaneously.
Different healthcare systems and clinical indications may use exome sequencing, genome sequencing or targeted analysis depending on current practice.
What is whole-genome sequencing?
Whole-genome sequencing, usually shortened to WGS, reads DNA across the genome much more broadly.
Current NICE guidance recommends considering WGS for the particular epilepsy groups described earlier.
However, “whole genome” does not mean that every difference in a person's DNA is automatically interpreted and reported.
Clinical analysis is usually focused on genetic changes relevant to the person's medical problem and the current test specification.
NHS genomic testing is deliberately targeted towards results that are likely to influence the person's or family's clinical management.
Why might parents be tested too?
Testing a child together with biological parents can sometimes be particularly useful.
This is often called trio testing.
If a variant is found in the child, parental samples can help determine whether it:
was inherited
appeared de novo
or fits a particular inheritance pattern.
This additional information can make variant interpretation more accurate.
Sometimes testing other relatives is also useful.
What is a chromosome microarray?
Not every important genetic change involves a single DNA letter.
Sometimes sections of DNA are:
missing
duplicated
or rearranged.
A chromosomal microarray can detect many copy-number changes — known as CNVs.
Current NHS epilepsy testing pathways may include genome-wide assessment for these types of changes where appropriate.
What is mosaicism?
A genetic variant does not always occur in every cell in the body.
If the change occurred after the first cell divisions of an embryo, only a proportion of cells may carry it.
This is called mosaicism.
Mosaic genetic changes are important in some neurological and developmental conditions.
The amount of a variant can also differ between tissues.
That can occasionally make a genetic cause harder to identify from an ordinary blood sample.
Specialist genomic teams decide whether additional or alternative testing is appropriate when mosaicism is suspected.
What happens before testing?
Genetic testing can have implications beyond the person being tested.
NICE therefore recommends discussing:
why the test is being performed
what information it might provide
possible limitations
and possible implications for the person and family
before testing takes place.
Informed consent and appropriate genetic counselling are required.
This matters because genomic results may provide information relevant to biological relatives as well as the individual.
What results can genetic testing produce?
There are several broad possibilities.
A causative result
A pathogenic or likely pathogenic variant may be found that fits the person's epilepsy and other clinical features.
This can establish a molecular diagnosis.
No causative result
No currently recognised disease-causing variant may be found.
This does not necessarily mean the epilepsy is non-genetic.
It means current testing and knowledge did not identify an explanation.
Variant of uncertain significance
A genetic difference may be found, but there is not enough evidence to know whether it causes disease.
This is known as a variant of uncertain significance, or VUS.
Occasionally, other findings
Broad genomic testing can sometimes identify information unrelated to the original reason for testing.
The potential for unexpected findings forms part of the consent conversation.
What does pathogenic mean?
A pathogenic variant is a genetic change for which there is strong evidence that it causes or contributes to disease in the appropriate clinical setting.
A likely pathogenic variant also has strong evidence of disease association, although the level of certainty is slightly lower.
Even then, the clinical team needs to check that the person's symptoms actually fit the condition associated with that gene.
A laboratory finding that does not fit the person's clinical presentation should not simply be forced into becoming the diagnosis.
What is a variant of uncertain significance?
A VUS is a genetic change for which current evidence cannot confidently determine whether it is harmless or disease-causing.
This is not the same as a positive diagnosis.
NHS Genomics Education guidance is very clear:
a VUS is not clinically actionable and should not be used on its own to change treatment or management.
This distinction is extremely important.
Why can a VUS change classification later?
Genetic science develops quickly.
A rare variant might initially have been seen in only one or two people.
Later, researchers may discover it in:
many people with the same condition
healthy people without the condition
affected relatives
or laboratory experiments that clarify what the variant does.
As evidence accumulates, a VUS may eventually be:
upgraded towards likely pathogenic/pathogenic
or downgraded towards likely benign/benign.
Current NHS guidance notes that laboratories cannot necessarily monitor every VUS indefinitely, so families may sometimes be advised to re-consult in future if the result remains important.
Can relatives be tested after a VUS?
Sometimes family samples are requested specifically to help determine what the VUS means.
For example, doctors may want to know whether it is present in:
an affected parent
unaffected relatives
siblings
or other family members.
But this is different from using a VUS for predictive testing.
A VUS should not normally be used to tell healthy relatives that they are or are not at risk of disease.
What does a negative genetic test mean?
A negative result means:
the test has not identified a currently recognised genetic cause.
It does not necessarily mean:
there is definitely no genetic cause.
Possible reasons include:
the responsible gene has not yet been discovered
current technology cannot detect the particular variant
the variant lies in a region not adequately analysed
mosaicism is difficult to detect
several genetic factors are contributing rather than one
or the epilepsy has a non-genetic cause.
Genomics Education guidance specifically emphasises that failure to identify a causative result does not exclude an underlying genomic cause.
Can a genetic diagnosis change treatment?
Sometimes — and this is one of the most important reasons testing can matter.
A genetic diagnosis may identify a biological mechanism that makes particular treatments:
more appropriate
less appropriate
or potentially harmful.
This is sometimes described as precision medicine.
It does not mean every genetic epilepsy currently has a gene-specific treatment.
Most do not.
But there are important examples where the diagnosis influences management.
Dravet syndrome is one example
Dravet syndrome is commonly associated with pathogenic variants affecting SCN1A.
Identifying the syndrome matters because treatment choices differ from those used in many other epilepsies.
Current NICE guidance specifically warns that several medicines may exacerbate seizures in people with Dravet syndrome, including:
carbamazepine
lacosamide
lamotrigine
oxcarbazepine
and several others.
NICE also provides syndrome-specific treatment pathways including valproate, clobazam/stiripentol, fenfluramine and cannabidiol with clobazam in appropriate circumstances.
Genetic testing therefore may do more than simply give the condition a name.
It can help prevent inappropriate treatment.
GLUT1 deficiency is another important example
Glucose transporter type 1 deficiency syndrome, usually called GLUT1 deficiency, is commonly associated with pathogenic variants in SLC2A1.
The condition interferes with transport of glucose into the brain.
Because of that mechanism, the ketogenic diet can provide an alternative fuel source through ketones.
The ketogenic diet is considered a particularly important mechanism-directed treatment in GLUT1 deficiency.
This is a strong example of how finding a genetic cause can fundamentally change treatment thinking.
Genetics can identify conditions beyond epilepsy
Sometimes seizures are one feature of a wider genetic condition.
Examples include:
tuberous sclerosis complex
Rett syndrome
neurofibromatosis type 1
Fragile X syndrome
and many metabolic or developmental disorders.
A genetic diagnosis may therefore lead doctors to monitor things that extend beyond seizures.
That might involve:
development
movement
heart
kidneys
eyes
growth
behaviour
or other systems,
depending entirely on the condition identified.
Can a genetic result predict how severe epilepsy will become?
Sometimes it provides useful information, but predictions are rarely perfect.
Two people with variants in the same gene can have very different:
seizure types
seizure severity
development
learning abilities
age of onset
treatment responses
and long-term outcomes.
Even people carrying exactly the same variant can be affected differently.
A genetic diagnosis can narrow uncertainty.
It does not turn an individual's future into a certainty.
Can genetic testing tell whether a child will inherit epilepsy?
Sometimes it can provide much more precise information.
If a specific disease-causing variant and inheritance pattern are known, a genetics team may be able to estimate the chance of passing that variant to a child.
But passing on a variant is not always the same as predicting that the child will definitely develop epilepsy.
Reduced penetrance and variable expression can complicate the picture.
Epilepsy Action notes that most children of parents with epilepsy do not themselves develop epilepsy and that individual risk depends on the particular epilepsy and genetic cause.
What if neither parent carries the variant?
If testing confirms that a disease-causing variant arose de novo, this can substantially change the estimated risk for other family members.
However, recurrence risk is not always exactly zero.
Rarely, a parent can have germline mosaicism, meaning some egg or sperm cells carry the variant even though ordinary blood testing does not detect it.
A clinical geneticist or genetic counsellor can explain the specific recurrence risk for the condition involved.
What if a parent carries the same variant but has no epilepsy?
That does not automatically mean the result is wrong.
Possible explanations include:
reduced penetrance
variable expression
age-related effects
or other genetic and environmental modifiers.
The clinical team has to interpret the variant in the context of the whole family.
This is another reason genomic interpretation is more complex than simply finding a spelling difference in DNA.
Can genetics explain epilepsy that appears to run in a family?
Sometimes.
A family history may be an important clue.
Doctors may ask about:
epilepsy
childhood febrile seizures
unexplained collapses
developmental conditions
movement disorders
intellectual disability
autism
migraine
or other neurological problems.
Different relatives may have different manifestations of the same underlying genetic condition.
A detailed family tree can therefore be useful during genetics assessment.
Does having no family history make testing pointless?
No.
De novo variants are particularly important in many severe childhood genetic epilepsies.
A completely negative family history does not rule out a genetic cause.
The person's:
age of onset
seizure type
development
EEG
MRI
physical features
cognitive profile
and other medical problems
may be much more informative than family history alone.
Can genetic testing replace EEG or MRI?
No.
Genetic testing answers a different question.
EEG asks:
What is the brain's electrical activity doing?
MRI asks:
Is there a structural brain abnormality?
Genetic testing asks:
Is there a genomic change that helps explain why this epilepsy developed?
A person may need several of these investigations.
Related Information Hub pages:
EEG: What It Can — and Cannot — Tell You About Epilepsy
MRI and Epilepsy: What Doctors Are Looking For
Can someone have both a structural and genetic cause?
Yes.
These categories are not always completely separate.
A genetic variant can itself cause abnormal brain development.
For example, some genetic conditions produce:
cortical malformations
tubers
abnormal brain growth
or other structural changes visible on MRI.
So the MRI may show what developed differently, while genetics may help explain why it developed differently.
What about focal epilepsy with a normal MRI?
Genetics may sometimes still be relevant.
Historically, genetic testing was associated most strongly with severe childhood epilepsies.
But increasing numbers of genes are now known to cause focal epilepsy, sometimes with:
normal development
normal MRI
and several affected family members.
Whether NHS testing is appropriate depends on the clinical picture and current testing criteria.
Could genetic testing prevent years of repeated investigations?
Sometimes.
A clear genetic diagnosis can bring an end to what is sometimes called a diagnostic odyssey — years of repeated appointments and investigations trying to explain a person's symptoms.
It may allow clinicians to stop looking for unlikely alternative causes and instead focus on:
appropriate treatment
surveillance
development
family counselling
and support.
The NHS National Genomic Test Directory specifically targets testing towards situations where a result may guide management for the person or their family.
But a diagnosis can also create new questions
Receiving the name of a genetic condition can bring relief because there is finally an explanation.
It can also raise difficult questions about:
future health
children
siblings
parents
prognosis
treatment
and what other family members should be told.
There is no single correct emotional reaction to a genetic diagnosis.
Genetic counselling exists partly to help people understand these implications rather than simply handing over a laboratory report.
What is genetic counselling?
Genetic counselling provides information and support around genomic conditions and testing.
A genetic counsellor or clinical geneticist can help explain:
what the test found
how confident the result is
how the condition may be inherited
what it means for relatives
reproductive choices
whether other family members should be tested
and what is still uncertain.
NICE requires appropriate genetic counselling and informed consent before genomic testing for epilepsy.
Should children be tested just because a parent has epilepsy?
Not automatically.
If a parent has epilepsy but no specific inherited genetic diagnosis has been identified, there may be nothing useful to test for in an otherwise healthy child.
Predictive testing of children raises separate ethical and medical considerations.
If a known disease-causing familial variant exists, the genetics team can advise:
whether testing is appropriate
at what age
and whether the result would change medical care.
Can someone order an epilepsy genetic test privately?
Commercial genetic tests are available, but their quality and usefulness vary.
A broad consumer DNA test is not the same as clinical genomic testing performed through an accredited medical laboratory.
Clinical interpretation requires knowledge of:
the person's seizures
EEG
MRI
development
family history
and current scientific evidence.
A result from a commercial service should not be used independently to change antiseizure treatment.
Why shouldn't raw DNA data be interpreted casually online?
Every person has millions of genetic variants.
Most are harmless.
Finding that a person has a difference in a gene associated with epilepsy does not automatically mean that difference causes epilepsy.
Variant interpretation requires evidence from:
population databases
laboratory studies
inheritance patterns
published cases
computational evidence
and the person's clinical features.
Incorrectly labelling a harmless variant as pathogenic can lead to:
incorrect diagnosis
unnecessary anxiety
inappropriate medication changes
and incorrect advice to relatives.
NHS genomics guidance emphasises that only appropriately classified pathogenic or likely pathogenic findings should be used for clinical decision-making.
Genetic knowledge changes over time
This field moves quickly.
A person tested many years ago may have received:
“No genetic cause identified.”
That result may have been based on:
fewer known epilepsy genes
older sequencing technology
more limited analysis
or testing of only one gene.
In selected situations, specialists may consider whether updated testing or reinterpretation could now be useful.
A previous negative result is therefore not necessarily the final word forever.
Questions to ask before genetic testing
Useful questions include:
Why do you think my epilepsy might be genetic?
What test are you requesting?
What could a positive result change?
Could it affect my treatment?
Could the result have implications for my family?
Could the test produce an uncertain result?
What happens if nothing is found?
Who will explain the result to me?
Would my parents or other relatives need testing?
Could the result affect future pregnancy planning?
Questions to ask when the result comes back
Useful questions include:
Was a definite genetic cause identified?
Is the variant pathogenic, likely pathogenic or uncertain?
Does this gene actually fit my epilepsy and other symptoms?
Was the variant inherited or de novo?
Does this diagnosis change my treatment?
Are there medicines I should avoid?
Does the condition affect any organs or systems besides the brain?
Do I need additional monitoring?
Should relatives be offered testing?
What does this mean if I want children?
Could the result be reinterpreted in the future?
The most important message
Genetic testing is becoming an increasingly important part of epilepsy diagnosis.
But genetic epilepsy is not one single thing.
Some epilepsies result from one disease-causing variant.
Others involve many genetic factors.
Some variants are inherited.
Others arise de novo.
And some people with a strong genetic epilepsy will still receive a negative genetic test because current science has not identified the precise cause.
A useful genetic diagnosis can sometimes:
give a condition a specific name
prevent unnecessary further investigation
influence treatment
identify medicines that may worsen a syndrome
reveal other health issues that need monitoring
and give families more accurate information about inheritance.
But not every genetic finding is an answer.
A variant of uncertain significance is exactly that — uncertain. It should not be used by itself to change treatment.
Genetic testing is most useful when the laboratory result is combined with the person standing behind it:
their seizures, development, family history, EEG, MRI and complete clinical story.
Sources and further reading
NICE — Epilepsies in children, young people and adults (NG217): Genetic testing.
Current NICE guidance sets out who should be considered for genomic testing, including early-onset epilepsy, suspected genetic epilepsy syndromes, learning disability, autism, structural abnormalities and unexplained cognitive decline. It also requires informed consent and appropriate genetic counselling. Last updated January 2025.
NHS England — National Genomic Test Directory.
The Test Directory defines genomic tests funded within the NHS in England and their eligibility criteria. The rare and inherited disease directory was updated in 2026 and is reviewed as genomic knowledge and clinical utility develop.
NHS Genomics Education Programme — National Genomic Test Directory.
Explains the different genomic technologies and the principle that testing should be targeted where a result can guide clinical or family management. Reviewed March 2026.
NHS Genomics Education Programme — Variants of uncertain significance.
Current NHS guidance explains that a VUS does not provide a genetic diagnosis and is not clinically actionable. Reviewed August 2026.
Epilepsy Action — Genetics and epilepsy.
UK information covering genetic and inherited epilepsy, genetic testing, de novo variants, genetic epilepsy syndromes and possible test results. Last modified February 2026.
NICE — Treatment of Dravet syndrome.
Current guidance illustrates how identifying a specific epilepsy syndrome can alter treatment, including medicines that may exacerbate seizures in Dravet syndrome and syndrome-specific treatment choices.
Information reviewed: September 2026.
This page provides general educational information. Genomic results should be interpreted by healthcare professionals with appropriate expertise and in the context of the individual's clinical history. Do not change antiseizure treatment because of a genetic result without specialist advice.
