Currently, there are no curative or truly disease-modifying treatments for SCN2A-related disorders. There is, however, some evidence that currently-available AEDs can improve seizure control. However, it is important to note that because there have been no clinical trials of AEDs in SCN2A-related disorders, the following information should be taken with caution. Furthermore, the response to AEDs appears to vary between different SCN2A phenotypes, meaning treatments thought to benefit one phenotype should not be assumed to be beneficial for other SCN2A phenotypes.
It is recommended that an individual with an SCN2A-related disorder with epilepsy or a movement disorder is managed by a neurologist.
Treatment of SCN2A-related disorders with epilepsy
Improvement with sodium channel blockers (SCBs), particularly phenytoin (PHT), is reported in the severe and intermediate neonatal/infantile phenotypes. PHT appears the most effective SCB, although improvement with other SCBs including lacosamide and carbamazepine is reported.
Benefit from these drugs is not universal, and there are some reports of exacerbation or other symptoms such as movement disorders despite improved seizure control. The reasons for these apparently differential responses to SCBs are not known. Although PHT may improve seizures, it does not appear to significantly improve developmental outcomes. Some PHT-responsive individuals may require supra-therapeutic serum PHT levels before a reduction in seizure frequency is seen. The degree of reported improvement in seizure frequency can be variable over time for an individual. Seizure exacerbations (often as clusters of seizures, sometimes meeting definitions of status epilepticus) may occur in the context of low PHT levels.
Seizures in BFNIS are typically treatment-responsive, and benefit with non-SCB AEDs is reported. In fact, the response to SCBs in BFNIS is not specifically reported, although individuals with epilepsy preceding EA (some of whom have an epilepsy phenotype consistent with BFNIS) appear to benefit from SCBs.
Mid-late infancy-onset phenotypes
The response to SCBs in this phenotype is unclear and needs further study, with exacerbations, no change and benefit in seizure control all reported. There are a number of reports of effective treatment of spasms with corticosteroids, although this response is not universal. Most affected individuals have ongoing seizures (variable types), and no single AED is consistently reported to be of benefit.
Treatment response in this phenotype is not well-defined; no particular AED is consistently reported to be beneficial.
Treatment of non-epilepsy manifestations
Non-epilepsy manifestations of SCN2A-related disorders such as DD/ID, sleep disorders, emotional or behavioural disorders, movement disorders, abnormalities of tone and gastrointestinal symptoms can cause considerable morbidity. Prompt recognition and appropriate management of such symptoms can significantly improve quality of life.
Close developmental surveillance should be undertaken, with early referral for developmental and behavioural intervention and support made where relevant. Specialist schooling and ongoing allied health interventions is required for many individuals with a SCN2A-related disorder. Prompt referral to an expert in the emotional and mental health needs of individuals with neurodevelopmental disorders should be made if there are concerns with challenging behaviours or changes in the emotional well-being of affected individuals. Regular review with a paediatrician or physician with expertise in the support of children or adults with a neurodevelopmental disorder is recommended.
Referral to a neurologist is recommended for individuals with movement disorders such as dystonia and episodic ataxia (EA). At this stage, the most effective treatment for SCN2A-related movement disorders is not known. There are reports of improvement with carbamazepine and acetazolamide in some individuals with EA, but others showed no benefit.
Gastrointestinal symptoms may be treated with anti-reflux medications (reflux) or aperients (constipation). If symptoms are problematic despite this, referral to a gastroenterologist could be considered.
SCN2A-related disorders in which seizures may be absent
Intellectual disability and/or autism
As with other causes of DD/ID or ASD, early developmental and behavioural intervention and ongoing specialist schooling, social skills support, community programs and allied health therapies are important to maximise cognitive and social potential and emotional wellbeing. It is recommended that regular review with a paediatrician or physician with expertise in the support of children or adults with a neurodevelopmental disorder occurs. Surveillance should be undertaken for comorbidities such as hypotonia, disordered sleep and gastrointestinal symptoms, and symptoms promptly managed where present. No SCN2A-specific treatments that specifically target neurodevelopmental, cognitive or behavioural symptoms are currently known.
No treatment has been shown to consistently reduce the frequency or severity of episodes of ataxia. Some individuals have reported improvement with carbamazepine or acetazolamide, but others have reported no benefit.
There are a number of support groups for SCN2A-related disorders, including:
FamilieSCN2A Foundation (US-based): www.scn2a.org
SCN2A Australia: www.scn2aaustralia.org
Many other countries have SCN2A support groups that do not have a website, most being closed Facebook groups. These can be found by searching the Facebook site and requesting to join the group.