Knowledge base · plain-language guide

Understanding genetics and diagnosis.

When your child receives a diagnosis linked to a gene like SCN2A, or when a genetic test returns a result that requires interpretation, it can feel as though you are suddenly expected to understand an entirely new language. You don't need a science background to follow this guide.

The basics

What is a genetic condition?

Every person's body is built according to a set of instructions encoded in DNA. These instructions are organised into units called genes, each one responsible for a particular function in the body. Humans have tens of thousands of genes, and together they influence everything from eye colour to how the brain develops.

Sometimes, a gene contains a change, called a variant, that affects how it works. In the case of SCN2A and other genes associated with DEE, the relevant gene change affects how the brain develops and how its electrical activity is regulated.

Not all gene variants are significant. Some are common variations that don't affect health at all. Others, called pathogenic variants, are known to cause or significantly contribute to a health condition.

The pathway

How is a genetic condition diagnosed?

For most families, a genetic diagnosis follows a period of clinical concern, often after seizures, developmental delays, or other neurological features have prompted investigation.

Clinical assessment

A paediatric neurologist or developmental paediatrician assesses your child's presentation: their symptoms, development, and medical history. This guides which investigations are ordered.

Neurological investigations

An EEG (electroencephalogram) measures brain electrical activity and can identify abnormal patterns associated with epilepsy. Brain MRI may also be performed to look for structural abnormalities.

Genetic testing

If a genetic cause is suspected, genetic testing is recommended. This may take several forms:

Gene panel testing, a defined list of genes known to be associated with epilepsy or neurodevelopmental conditions. SCN2A is included in most epilepsy gene panels.
Whole exome sequencing (WES), analyses all the coding regions of all genes. Used when a gene panel has not identified a cause, or when the presentation is unusual.
Whole genome sequencing (WGS), the most comprehensive form of testing, examining the entire genome including non-coding regions.
Chromosomal microarray, detects larger deletions or duplications involving sections of a chromosome.

In Australia, genetic testing is typically arranged through a clinical genetics service or a paediatric neurologist.

Reading your results

The terms you'll see on a report.

Pathogenic variant

A gene change that is established to cause, or significantly contribute to, a health condition. If your child's report identifies a pathogenic SCN2A variant, this confirms a genetic basis.

Likely pathogenic variant

A gene change strongly suspected to be causative, though not yet confirmed with absolute certainty. Typically managed similarly to pathogenic variants.

Variant of uncertain significance (VUS)

A gene change has been identified, but current evidence is insufficient to classify it as either causative or benign. VUS results can be unsettling, know that classification can change over time as research advances.

Benign or likely benign variant

A gene change that is not considered to cause the condition. Typically not reported, or noted as incidental.

De novo variant

A gene change that was not inherited from either parent, it arose spontaneously, either during the formation of egg or sperm, or in early foetal development. The majority of SCN2A pathogenic variants are de novo.

Inherited variant

Some SCN2A variants, particularly those associated with milder presentations, are inherited from a parent who may carry the variant themselves, sometimes with little or no clinical impact (variable expressivity).

A note for families

A de novo variant is not caused by anything you did during pregnancy. These variants occur spontaneously and are not a result of any action or inaction on a parent's part.

Family planning

What does "de novo" mean for the rest of my family?

If your child's SCN2A variant is confirmed as de novo, the likelihood of the same variant occurring in a future sibling is low, approximately 1%, due to the small chance of the same spontaneous change occurring again. This is sometimes referred to as gonadal mosaicism: the possibility that a small number of egg or sperm cells in a parent carry the variant, even though a standard blood test did not detect it.

Given this small recurrence risk, families planning future pregnancies are encouraged to discuss options with a clinical genetics service before conception. Prenatal genetic testing is available for families in this situation.

If a variant is inherited rather than de novo, the recurrence risk is higher and depends on the inheritance pattern of the specific variant. A genetic counsellor can advise on this in the context of your family's specific result.

Genetic counselling

What is it, and why does it matter?

A genetic counsellor is a health professional specialising in genetic conditions. They are trained to help families understand what a genetic result means, for their child, for other family members, and for future family planning.

Genetic counselling is not just about understanding numbers and probabilities. It also helps families process the emotional aspects of receiving a genetic diagnosis and make informed decisions about testing, management, and family planning.

SCN2A Australia can help connect you with a clinical genetics service or genetic counsellor experienced in neurodevelopmental conditions. If your child's treating team has not yet arranged genetic counselling, it is worth requesting a referral.

Treatment safety

Why GoF vs LoF matters for treatment.

One of the most clinically important questions for any family with an SCN2A diagnosis is whether the variant is a gain of function (GoF) or loss of function (LoF) variant. This distinction affects which anti-seizure medications are likely to be helpful, and which may need to be avoided.

GoF variants make the sodium channel more active than it should be. Medications that calm channel activity (sodium channel blockers such as phenytoin or carbamazepine) are often effective.
LoF variants make the sodium channel less active. The same sodium channel-blocking medications may worsen symptoms.

Important

If you are unsure whether your child's variant is gain or loss of function, ask your neurologist directly. This information should be clearly documented in your child's medical records and communicated to any clinician, including in emergency settings, who may be prescribing medication.

Still searching?

Awaiting a diagnosis.

For many families, the path to a confirmed genetic diagnosis is not straightforward. It may involve multiple rounds of testing, second opinions, and a period of living with uncertainty. A "variant of uncertain significance" result, or a normal genetic test result despite a clear clinical picture, does not mean that something is not wrong, it means that current testing has not yet identified the cause.

Genetic testing technology is improving rapidly. Variants that cannot be explained today may be reclassified as research advances, and whole genome sequencing is identifying causes in families where earlier tests found nothing.

SCN2A Australia can help you navigate the diagnostic process, whether you are still seeking a diagnosis, trying to understand a recent result, or considering further testing.

We can help

Understanding a genetic result is one of the most common reasons families contact us.

We can help you read your child's report in plain language, connect you with a genetic counsellor, link you with SCN2A-experienced clinicians, or help you prepare questions for your next appointment.