SCN2A-related conditions are neurodevelopmental conditions caused by genetic changes in the SCN2A gene.^1,2 The SCN2A gene produces the Nav1.2 protein that controls signalling of nerve cells (neurons) in the brain. Changes in SCN2A gene affects the development and function of the brain and nervous system.

SCN2A-related conditions include a wide range of symptoms that primarily affect brain function but can affect other body systems. The symptoms may include seizures, developmental delay, movement disorders, gastrointestinal problems, behavioural attributes, sleep issues and others.^1-4,6,7 These symptoms and severity can vary widely between individuals and may depend on their genetic variant. With advancement in genetic testing and research, more symptoms and genetic variants of SCN2A-related conditions are being recognised and more well understood over time.

SCN2A-related condition is more commonly diagnosed in babies or young children, and have been reported to be under-diagnosed or misdiagnosed in adults and individuals without epilepsy.²

Synonyms: developmental and epileptic encephalopathy 11, DEE11, epileptic encephalopathy early infantile 11, EIEE11, early infantile epileptic encephalopathy caused by mutation in SCN2A.⁴

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

There is no known ORPHAcode or ICD:11 classification for SCN2A-related conditions.

Symptoms and severity of SCN2A-related conditions vary widely between individuals.

Individuals with SCN2A-related conditions often have:^1-4,6,7

• seizures – this can vary in terms of presence of seizures, type, frequency and severity, and may affect the whole body or certain parts of the body (focal seizures)
• intellectual disability ranging from mild to severe
• developmental delay
• difficulties with communications such as non-verbal or speech delay
• movement disorders such as dystonia, episodic ataxia, involuntary movements, and low muscle tone (hypotonia)
• gastrointestinal problems such as reflux, constipation or diarrhoea
• scoliosis
• cerebral/cortical vision impairment (CVI)
• behavioural attributes such as autism, repetitive actions, poor eye contact, difficulty with social interactions difficulty going to sleep and staying asleep

In some cases, some of the symptoms and features tend to occur together, and may be recognised as the following:

Self-limited familial neonatal-infantile epilepsy (SeLFNIE) – characterised by seizures that begin soon after birth, that usually respond well to medications or resolve on its own.² Seizures typically stop within the first few years.^2,4 Individuals usually have unaffected development, cognitive and intellectual ability.

Developmental epileptic encephalopathy (DEE) – DEE is most common among SCN2A-related conditions.³ It is characterised by severe epilepsy that are often difficult to treat and control. Individuals often have global developmental delay, intellectual disability, neurological symptoms, difficulties with movement, feeding, sleeping and vision.² DEE can be further differentiated into early-infantile DEE (seizures starting before 3-months old) and later-onset DEE (after 3-months old).

Intellectual disability and/or autism with or without epilepsy – Individuals often appear to be developing well in the first 6 months.⁴ Characteristics such as global developmental delay (especially motor, speech and social skills), intellectual disability, and autism becomes more apparent after that.² Other symptoms include uncoordinated movements, problems with gastrointestinal system, sleep, oral and vision. Most people do not have seizures, however in some people, they develop seizures later during childhood.^3,4

Episodic ataxia – describes periods of poor coordination or balance, which may last minutes to hours. Frequency may vary widely between individuals. Most children have early-onset seizures, with unaffected cognitive and intellectual ability.²

Please speak to your medical team to learn more about the signs and symptoms of SCN2A-related conditions.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

SCN2A-related condition is a genetic condition, caused by disease-causing genetic changes (variants) in the SCN2A gene on chromosome 2.¹ The SCN2A gene is responsible for producing the Nav1.2 protein, a sodium channel that controls how nerve cells (neurons) transmit signals in the brain. These signals are important for nervous system function, and affects our movement, sensation and responses to the environment.

Variants in the SCN2A gene can cause neurons to be more active (gain of function/GOF variants) or less active (loss of function/LOF variants) than they should be, leading to a spectrum of neurodevelopmental symptoms.^1,2,8 More information about GOF and LOF variants can be found at SCN2A Australia: Gain & Loss of Functions Information Sheet.

For most individuals with SCN2A-related condition, their genetic variants occur randomly (de novo) prior to birth and is not passed down (inherited) from their parents.^1,6

In some cases, the SCN2A variant is passed down from a parent who has the genetic change in some but not all of their cells (this is called genetic mosaicism); the parent often has no to mild symptoms.^4,9 More information on genetic mosaicism can be found at Centre for Genetics Education: Mosaicism

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of SCN2A-related condition may be made based on:^4,7

• physical examination
• family history
• electroencephalogram (EEG) to look for abnormal brain activity and seizures
• imaging tests such as magnetic resonance imaging (MRI) to look for structural brain abnormalities
• genetic testing to look for genetic variants in SCN2A gene

As part of the diagnostic process, doctors may do a differential diagnosis, where they rule out other conditions that have similar symptoms, such as KCNT1-related disorder, KCNQ2-related disorder, PRRT2-related epilepsy, SCN8A-related epilepsy.²

Please speak to your medical team to learn more about the available diagnostic pathways for SCN2A-related conditions.

There is currently no curative treatment for SCN2A-related conditions. Treatment is targeted at managing symptoms and in some cases, may be tailored depending on their genetic variant.² This may include:^1-4,6-9

• seizure management – this may vary between individuals depending on their genetic variant, age of seizure onset, types of seizure and suitability of treatment
• feeding therapy and use of feeding tube
• physical therapy and occupational therapy
• speech therapy
• vision aid
• mobility aid
• early developmental and behavioural interventions

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the care of people with SCN2A-related conditions may include general practitioners (GP), paediatricians, neurologists, epileptologists (neurologists that specialise in epilepsy management), gastroenterologists, endocrinologists, dietitians, orthopaedists, otolaryngologists, physiotherapists, occupational therapists, speech pathologists, psychiatrists, nephrologists, urologists and others.^1-3 The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. Palliative care is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. For more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

We are not aware of any official clinical care guidelines for SCN2A-related condition in Australia or internationally. If you know of any relevant clinical care guidelines, please let us know via the Contribute page.

The following resources include clinical management for health professionals:

• NSW Centre for Genetics Education: Health condition caused by changes in the SCN2A gene includes management recommendations, updated in 2022.

• Human Disease Genes Website Series: SCN2A Management developed by Australian health professionals to provide clinical information about SCN2A-related conditions, updated in 2023.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

It may be important to consider the following when managing individuals living with SCN2A-related conditions at emergency departments/services:

• may be non-verbal, and may need assistance with communication
• may be prone to seizures if unwell
• may have challenging behaviours if distressed
• may have an emergency medication management plan that has been endorsed by their usual medical practitioner

SCN2A Australia: Research has information on SCN2A-related research in Australia and overseas.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Australian Organisation:
SCN2A Australia
Website: https://scn2aaustralia.org/
SCN2A Australia’s mission is to improve the lives of individuals and families affected by SCN2A-related disorders. They are dedicated to raising awareness, providing support, fostering research, and advocating for better resources and treatments.

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

SCN2A-related conditions vary between individuals, and each person’s experience is unique.

Personal stories shared with RVA: Jacob’s story, Eva’s story, Gabriela’s story, Lachy’s story

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

SCN2A Australia: Resources have links to relevant resources on common symptoms, financial, disability and NDIS disability support for people living with SCN2A-related conditions.

Epilepsy Smart Australia: National Epilepsy Support Service is a free, Australia-wide resource that provides support and information for people living with epilepsy.

Epilepsy Foundation: Epilepsy and Seizure Management Tools

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on SCN2A-related conditions can be found at:

• SCN2A Australia: Information Sheets
• NSW Centre for Genetics Education: Health condition caused by changes in the SCN2A gene
• Epilepsy Foundation: Genetic Epilepsies
• Epilepsy Smart: Developmental and epileptic encephalopathy (DEE)
• Unique Understanding chromosome disorders: SCN2A related conditions

Online Mendelian Inheritance in Man, OMIM^®:#613721 Developmental and epileptic encephalopathy 11; DEE11

Online Mendelian Inheritance in Man, OMIM®:*182390 Sodium voltage-gated channel, alpha subunit 2; SCN2A

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with SCN2A Australia.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.