No two people with an SCN2A variant are affected in exactly the same way. Some experience frequent seizures from infancy; others have milder presentations with autism spectrum features and few or no seizures. Understanding where your family member sits within this spectrum, and why, is one of the things we can help you navigate.
What does the SCN2A gene do?
The SCN2A gene carries the instructions for making a protein called Nav1.2, a sodium channel that plays a critical role in brain cell communication.
Nav1.2 acts like a gateway in the walls of neurons (brain cells). It controls the movement of sodium into the cell, which triggers the electrical signals that allow neurons to communicate, to "fire", and send messages across the brain and to the rest of the body.
When Nav1.2 works as it should, this electrical activity is precisely regulated. When the SCN2A gene has a pathogenic variant, Nav1.2 may not function correctly, and that balance can be disrupted.
Gain of function and loss of function, what's the difference?
Not all SCN2A variants cause the same type of disruption. Understanding the difference matters because it directly affects which treatments are most likely to help.
This distinction is not just theoretical. Some anti-seizure medications that help people with gain-of-function variants may worsen symptoms in those with loss-of-function variants, which is why genetic diagnosis matters so much for guiding treatment decisions.
What symptoms can SCN2A-related disorders cause?
Because SCN2A variants can cause both overactivity and underactivity of the sodium channel, the range of symptoms is broad. Common features include some or all of the following:
Seizures
Seizures are the most frequently reported feature, particularly in gain-of-function variants. They may begin in the neonatal period (first 28 days) or early infancy, and can include focal, tonic, clonic, or other seizure types. Seizure severity and frequency vary significantly.
Developmental delay and intellectual disability
Many individuals with SCN2A variants experience some degree of developmental delay. This may affect motor development, language acquisition, cognitive development, or a combination. The degree varies widely across the SCN2A spectrum.
Autism spectrum disorder (ASD)
ASD features are particularly common in individuals with loss-of-function variants. Some individuals with SCN2A variants have a diagnosis of ASD with minimal seizure activity.
Movement difficulties
Some individuals experience movement disorders, including hypotonia (low muscle tone), ataxia, or difficulties with coordination.
Sleep disturbances
Sleep problems are common across the SCN2A community and can significantly affect quality of life for the individual and their family.
Gastrointestinal problems
Feeding difficulties, reflux, and constipation are reported by many families, particularly in individuals with more complex presentations.
How is SCN2A diagnosed?
SCN2A-related disorders are diagnosed through genetic testing, specifically, identification of a pathogenic or likely-pathogenic variant in the SCN2A gene. This is most commonly identified through:
- Chromosomal microarray (detects large deletions or duplications)
- Gene panel testing (tests a defined set of epilepsy or neurodevelopmental genes, including SCN2A)
- Whole exome sequencing (WES) or whole genome sequencing (WGS) (broader analysis that can identify variants not covered by a panel)
Most families reach a diagnosis after a period of investigation, often following the onset of seizures or developmental concerns. For some families, diagnosis takes months or years. For others, increasingly, newborn screening or early genetic testing is accelerating diagnosis.
If your family is still awaiting a diagnosis, or if you have had a genetic result you don't fully understand, our team can help you connect with a genetic counsellor or an SCN2A-experienced clinician.
What treatment options are available?
There is currently no cure for SCN2A-related disorders. Treatment is focused on managing symptoms, reducing seizure frequency, and supporting development and quality of life.
Anti-seizure medications (ASMs)
Medication selection for seizures requires careful consideration of variant type. For gain-of-function variants, sodium channel blockers (such as phenytoin or carbamazepine) are often used. For loss-of-function variants, the same medications may worsen the condition, making accurate genetic diagnosis essential before treatment decisions.
Early intervention and therapies
Early intervention programmes, occupational therapy, speech pathology, and physiotherapy are valuable for supporting development in children with SCN2A-related disorders. Earlier engagement typically leads to better developmental outcomes.
Multidisciplinary care
Most individuals with SCN2A-related disorders benefit from a coordinated care team that may include a paediatric neurologist, developmental paediatrician, geneticist, genetic counsellor, occupational therapist, speech pathologist, and psychologist.
Research and emerging treatments
Research into precision-medicine approaches, including antisense oligonucleotides (ASOs) and other targeted therapies, is advancing rapidly. SCN2A Australia tracks and translates this research for families. Several clinical trials have been conducted or are in development specifically for SCN2A.
How common is SCN2A?
SCN2A-related disorders are rare. Exact prevalence figures are still being established through natural-history research, but SCN2A is considered one of the more commonly identified single-gene causes of early infantile epileptic encephalopathy.
Because the condition exists on a spectrum, from severe early-onset epilepsy to autism with no seizures, it is likely underdiagnosed in individuals with milder presentations. Improved access to genetic testing is helping to identify more families.