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SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders

, PhD, , BA, and , MD.

Author Information and Affiliations

Initial Posting: ; Last Update: April 6, 2023.

Estimated reading time: 43 minutes


Clinical characteristics.

SCN8A-related epilepsy and/or neurodevelopmental disorders encompasses a spectrum of phenotypes. Epilepsy phenotypes include developmental and epileptic encephalopathy (DEE) associated with severe developmental delays and usually pharmacoresistant epilepsy with multiple seizure types; mild-to-moderate developmental and epileptic encephalopathy (mild/modDEE, or intermediate epilepsy) with partially treatable epilepsy; self-limited familial infantile epilepsy (SeLFIE, also known as benign familial infantile epilepsy or BFIE) with normal cognition and medically treatable seizures; neurodevelopmental delays with generalized epilepsy (NDDwGE); and neurodevelopmental disorder without epilepsy (NDDwoE) with mild-to-moderate intellectual disability (though it can be severe in ~10% of affected individuals). Hypotonia and movement disorders including dystonia, ataxia, and choreoathetosis are common in some phenotypes. Sudden unexpected death in epilepsy (SUDEP) has been reported in some affected individuals.


The diagnosis of SCN8A-related epilepsy and/or neurodevelopmental disorders is established in a proband with suggestive findings and a heterozygous pathogenic variant in SCN8A identified by molecular genetic testing.


Treatment – targeted therapy: Several studies suggest a favorable response to sodium channel blockers in the SCN8A-related epilepsy phenotypes of SCN8A-DEE, SCN8A-mild/modDEE, and SCN8A-SeLFIE.

Treatment – supportive care: Seizure control should be managed by a pediatric neurologist with expertise in epilepsy management who is familiar with the pharmacotherapy for SCN8A-related epilepsy and aware of how it differs from treatment of similar disorders. Vigorous attempts to control seizures are warranted. Supportive care to improve quality of life, maximize function, and reduce complications is recommended, ideally involving multidisciplinary care by specialists in relevant fields.

Surveillance: Periodic evaluations for neurologic, cognitive, and/or behavioral deterioration; monitoring with EEG and other modalities such as video EEG telemetry or ambulatory EEG when new or different seizure types are suspected. Because of the increased risk of SUDEP, monitoring seizures in individuals at higher risk, including those with generalized tonic-clonic seizures and/or nighttime seizures, is warranted.

Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify those who are at risk for developing seizures. This typically entails targeted molecular genetic testing for the known pathogenic variant(s) in the family.

Pregnancy management: Pregnant women should receive counseling regarding the risks and benefits of using anti-seizure medications during pregnancy; the advantages and disadvantages of increasing maternal periconceptional folic acid supplementation to 4,000 µg daily; the effects of pregnancy on anti-seizure medication metabolism; and the effect of pregnancy on maternal seizure control.

Agents/circumstances to avoid: Several families report worsening of seizures with levetiracetam.

Genetic counseling.

SCN8A-related epilepsy and/or neurodevelopmental disorders are inherited in an autosomal dominant manner. Individuals with more severe SCN8A-related phenotypes are more likely to have the disorder as the result of a de novo pathogenic variant than individuals with milder SCN8A-related phenotypes. Each child of an individual with SCN8A-related epilepsy and/or neurodevelopmental disorders has a 50% chance of inheriting the SCN8A pathogenic variant. Once the SCN8A pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

GeneReview Scope

SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders: Included Phenotypes

PhenotypeSCN8A-Related Disorder 1, 2
Epilepsy ± neurodevelopmental featuresDevelopmental and epileptic encephalopathy (DEE)
Mild-to-moderate developmental and epileptic encephalopathy (mild/modDEE, also referred to as intermediate epilepsy or IE 2)
Self-limited familial infantile epilepsy (SeLFIE, also referred to as benign familial infantile epilepsy or BFIE 2)
Neurodevelopmental disorder with generalized epilepsy (NDDwGE)
Neurodevelopmental disorderNeurodevelopmental disorder without epilepsy (NDDwoE)

For other genetic causes of these phenotypes, see Differential Diagnosis.



No consensus clinical diagnostic criteria for SCN8A-related epilepsy and/or neurodevelopmental disorders have been published.

Suggestive Findings

SCN8A-related epilepsy and/or neurodevelopmental disorders encompass a spectrum of phenotypes that range from mild to severe and should be considered in probands with the following clinical findings and family history.

Clinical Findings

Epilepsy features

  • Childhood-onset seizures: seizure onset variable, ranges from the first few months to the first few years of life
  • Development of multiple seizure types, including focal, multifocal, or generalized seizures
  • May be intractable in some individuals or treatable (especially using sodium channel blockers)

Clinical epilepsy syndromes reported in individuals with SCN8A-related epilepsy and/or neurodevelopmental disorders (see Clinical Characteristics). Five different clinical phenotypes have been identified in individuals with pathogenic SCN8A variants:

  • Developmental and epileptic encephalopathy (DEE). Severe intellectual disability, usually pharmacoresistant to anti-seizure medications
  • Mild-to-moderate DEE (mild/modDEE, also referred to as intermediate epilepsy or IE). Mild-to-moderate intellectual disability, partially treatable epilepsy
  • Self-limited familial infantile epilepsy (SeLFIE, also referred to as benign familial infantile epilepsy or BFIE). Normal cognition and medically treatable seizures (not necessarily self-limited)
  • Neurodevelopmental disorder with generalized epilepsy (NDDwGE). Mild-to-moderate intellectual disability, frequently with absence and other generalized seizures
  • Neurodevelopmental disorder without epilepsy (NDDwoE). Mild-to-moderate intellectual disability (can be severe in ~10% of affected individuals)

Other clinical features

  • Motor abnormalities including hypotonia in some individuals
  • Movement disorders including dystonia, ataxia, choreoathetosis, or paroxysmal kinesigenic dyskinesia in some individuals
  • Cognitive development varies depending on the clinical phenotype and can range from normal to severe cognitive delays. In some individuals, intellectual disability occurs without epilepsy.
  • Non-epileptic paroxysmal episodes, including startle-like myoclonus, generalized tremor, or hyperekplexia-like startles
  • Language delay, autism spectrum disorder, and behavioral issues may occur with certain epilepsy phenotypes or in the absence of epilepsy.
  • Some individuals have severe tone abnormalities, significant gastrointestinal issues, impaired swallow function, and cortical visual impairment with early mortality.

Family History

The proband may represent a simplex case (i.e., a single occurrence in a family) or the family history may suggest autosomal dominant inheritance (e.g., affected males and females in multiple generations). Probands with more severe SCN8A-related phenotypes are more likely to represent simplex cases.

Establishing the Diagnosis

The diagnosis of SCN8A-related epilepsy and/or neurodevelopmental disorders is established in a proband with suggestive clinical findings and a heterozygous pathogenic (or likely pathogenic) variant in SCN8A identified by molecular genetic testing (see Table 1).

Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and both can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this section is understood to include any likely pathogenic variants. (2) Identification of a heterozygous SCN8A variant of uncertain significance does not establish or rule out the diagnosis.

Molecular genetic testing in a child with epilepsy and/or developmental delay or an older individual with epilepsy and/or intellectual disability may begin with a multigene panel or exome sequencing. Subsequent testing may involve chromosomal microarray analysis (CMA); however, to date, there are very few reported copy number variants in this spectrum. Note: Single-gene testing (sequence analysis of SCN8A, followed by gene-targeted deletion/duplication analysis) is rarely useful and typically NOT recommended.

  • An epilepsy or intellectual disability multigene panel that includes SCN8A and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
  • Comprehensive genomic testing does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used and yields results similar to an epilepsy or intellectual disability multigene panel, with the additional advantage that exome sequencing includes genes recently identified as causing epilepsy or intellectual disability, whereas some multigene panels may not. To date, the majority of reported SCN8A pathogenic variants are within the coding region and are therefore likely to be identified on exome sequencing. Genome sequencing is also possible.
    For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders

Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
SCN8A Sequence analysis 3~99% 4
Gene-targeted deletion/duplication analysis 5~1% (very few reported to date) 4, 6

See Molecular Genetics for information on variants detected in this gene.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Small deletions and/or duplications in SCN8A have been rarely reported [Berghuis et al 2015, Larsen et al 2015, Wong et al 2021, Johannesen et al 2022].


To date, no large chromosomal deletions/duplications have been reported in individuals with SCN8A-related epilepsy and/or neurodevelopmental disorders.

Clinical Characteristics

Clinical Description

Five different clinical phenotypes have been identified in association with pathogenic SCN8A variants. Most individuals have features that fit into one of these five phenotypes:

  • Developmental and epileptic encephalopathy (DEE)
  • Mild-to-moderate developmental and epileptic encephalopathy (mild/modDEE, also referred to as intermediate epilepsy or IE)
  • Self-limited familial infantile epilepsy (SeLFIE, also referred to as benign familial infantile epilepsy or BFIE)
  • Neurodevelopmental disorder with generalized epilepsy (NDDwGE)
  • Neurodevelopmental disorder without epilepsy (NDDwoE)

To date, more than 500 individuals have been identified with a pathogenic variant in SCN8A [Rauch et al 2012, Veeramah et al 2012, Allen et al 2013, Carvill et al 2013, de Kovel et al 2014, Estacion et al 2014, Ohba et al 2014, Vaher et al 2014, Berghuis et al 2015, Blanchard et al 2015, Dyment et al 2015, Fitzgerald et al 2015, Fung et al 2015, Kong et al 2015a, Larsen et al 2015, Mercimek-Mahmutoglu et al 2015, Olson et al 2015, Singh et al 2015, Takahashi et al 2015, Wagnon et al 2015a, Anand et al 2016, Boerma et al 2016, Gardella et al 2016, Lelieveld et al 2016, Malcolmson et al 2016, McNally et al 2016, Møller et al 2016, Trump et al 2016, Arafat et al 2017, Braakman et al 2017, Butler et al 2017, Han et al 2017, Jain 2017, Parrini et al 2017, Rolvien et al 2017, Wagnon et al 2017, Wang et al 2017, Atanasoska et al 2018, Bagnasco et al 2018, Epilepsy Genetics Initiative 2018, Gardella et al 2018, Ko et al 2018, Kothur et al 2018, Lindy et al 2018, Liu et al 2018, Oates et al 2018, Pons et al 2018, Rim et al 2018, Tsang et al 2018, Wagnon et al 2018, Xiao et al 2018, Balciuniene et al 2019, Costain et al 2019, Denis et al 2019, Encinas et al 2019, Epifanio et al 2019, Jain et al 2019, Jang et al 2019, Johannesen et al 2019, Kim et al 2019, Liao et al 2019, Lin et al 2019, Liu et al 2019, Trivisano et al 2019, Wengert et al 2019, Xie et al 2019, Zaman et al 2019, Canafoglia et al 2020, Fatema et al 2020, Lee et al 2020, Mitta et al 2020, Pergande et al 2020, Ranza et al 2020, Schreiber et al 2020, Alagia et al 2021, Fan et al 2021, Negishi et al 2021, Solazzi et al 2021, Stringer et al 2021, Hu et al 2022, Johannesen et al 2022, Keshri et al 2022, Medlin et al 2022, Peng et al 2022].

The following description of the phenotypic features associated with this condition is based on these reports.

Table 2.

SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders: Comparison of Phenotypes by Select Features

FeatureSCN8A-Related Phenotype
Seizure types Focal, multifocal, bilateral tonic-clonic, tonic, or infantile spasmsFocal, multifocal, bilateral tonic-clonic, or tonicFocal, multifocal, bilateral tonic-clonic; may be self-limitingAbsence, bilateral tonic-clonic, or febrileNA
% w/epilepsy 100%100%100%100%0%
Median age of epilepsy onset ~3 months~5 months~6 months~42 monthsNA
Motor development Delayed, often nonambulatoryDelayedNormalDelayedDelayed
Speech development Delayed, often nonverbalDelayedNormal to mildly delayedDelayedDelayed
Cognition Moderate-to-severe IDMild-to-moderate IDNormal to mildly delayedNormal to severe ID (usually mild to moderate)Normal to severe ID
Other Hypotonia, CVI, ataxia, GI symptomsBehavioral issues, ataxiaParoxysmal kinesigenic dyskinesiaBehavioral issues, ADHD, ASDASD
Most common SCN8A variant type 1 GoFGoFGoFLoFLoF

ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; CVI = cortical visual impairment; DEE = developmental and epileptic encephalopathy; GI = gastrointestinal; GoF = gain of function; ID = intellectual disability; LoF = loss of function; NA = not applicable; NDDwGE = neurodevelopmental disorder with generalized epilepsy; NDDwoE = neurodevelopmental disorder without epilepsy; SeLFIE = self-limited familial infantile epilepsy


SCN8A-Related Developmental and Epileptic Encephalopathy (SCN8A-DEE)

Epilepsy. Age of seizure onset in affected individuals ranges from the first day of life to 22 months (median age: 3 months) [Johannesen et al 2022]. Seizures may occur prenatally, as some mothers reported unusual "drumming" movements in the later stages of pregnancy that are believed to be seizures [Singh et al 2015, Barker et al 2016, McNally et al 2016].

Initial seizure type varies, and most affected individuals develop additional seizure types over time, including the following:

  • Focal clonic seizures evolving to bilateral convulsive seizures
  • Generalized tonic-clonic seizures
  • Tonic seizures
  • Infantile spasms
  • Myoclonic seizures

Focal seizures in SCN8A-DEE are typically prolonged, with prominent hypomotor and autonomic symptoms [Gardella et al 2018] such as facial flushing, sialorrhea, bradycardia, and hypopnea, followed by tachycardia, polypnea, perioral cyanosis, and pallor [Trivisano et al 2019]. This may be followed by asymmetric tonic and clonic or hemiclonic phases, with or without bilateral tonic-clonic convulsions [Gardella et al 2018].

Although both convulsive and nonconvulsive status epilepticus appear to be common [Ohba et al 2014, Kong et al 2015a, Larsen et al 2015, Singh et al 2015, Wagnon et al 2015a, Wagnon et al 2015b, Braakman et al 2017, Gardella et al 2018, Kim et al 2019, Wengert et al 2019, Schreiber et al 2020, Donnan et al 2023], they are not as common as in Dravet syndrome (see SCN1A Seizure Disorders) and SCN2A-related epilepsy. A recent study of a small cohort of individuals with pathogenic SCN8A variants found that the median onset age of convulsive status epilepticus is around eight months, with a rate of 31% of affected individuals, and the median age of nonconvulsive status epilepticus is around 4.3 years, with a rate of 23% [Donnan et al 2023].

Seizure frequencies range from hundreds per day to fewer than one per month. Most affected individuals have refractory seizures and require polytherapy (see Treatment of Manifestations).

Psychomotor development varies from normal prior to seizure onset (with subsequent slowing or regression after seizure onset) to abnormal from birth [Larsen et al 2015, Gardella et al 2018, Denis et al 2019, Encinas et al 2019, Kim et al 2019, Schreiber et al 2020]. Many affected individuals experience marked slowing or arrest in development either for no apparent reason or after an event that occurred before the developmental decline, such as a change in seizure type or change in medication.

Approximately half of affected children learn to sit and walk unassisted; the remainder are nonambulatory. Ataxia and sudden loss of mobility are common in those who are ambulatory.

Most individuals diagnosed with this disorder are younger than age 20 years. For the several individuals who are in their teens, cognitive and motor disabilities persist. The oldest affected individual whom the authors are aware of is age 47 years [Authors, personal communication].

Language development is frequently affected. Most affected individuals speak few or no words and may exhibit anomic aphasia. Many individuals use nonverbal communication strategies as their primary expression method (e.g., crying, vocalizing, reaching/grabbing, behavioral aggression, movements).

Intellectual disability ranges from mild to severe, with about half of affected individuals having severe intellectual disability. Autistic features are noted in some individuals [Larsen et al 2015, Schreiber et al 2020].

Movement abnormalities including hypotonia, dystonia, choreoathetosis, ataxia, spasticity, and increased startle have been described in some affected individuals [Schreiber et al 2020].

Startle and sleep issues. Many children are hyperalert as infants (i.e., more awake and aware of their surroundings than typical infants) and are easily startled. For example, Singh et al [2015] reported a newborn with jittery movements shortly after birth and a pathologically exaggerated startle response to tactile and acoustic stimuli, findings that prompted a suspicion of hyperekplexia. The hyperalert sleep appears to make it difficult for the infant to settle into a deep, healthy sleep. These findings have been reported in several other individuals with SCN8A-DEE [Pons et al 2018].

Other associated features reported in some affected individuals include the following:

  • Autonomic nervous system dysfunction, including difficulty with temperature regulation and tachypnea
  • Hearing issues
  • Bone fractures, often associated with prolonged seizures
  • Laryngomalacia
  • Scoliosis
  • Microcephaly
  • Cortical visual impairment
  • Gum hyperplasia secondary to anti-seizure medication

Sudden unexpected death in epilepsy (SUDEP) has been reported in the literature [Veeramah et al 2012, Estacion et al 2014, Kong et al 2015a, Larsen et al 2015, Johannesen et al 2018, Denis et al 2019, Zaman et al 2019, Donnan et al 2023]. Johannesen et al [2018] examined the likely cause of death in 190 individuals and reported an overall mortality rate of 5.3%. Death was more frequently due to other causes, with definite SUDEP only ascertained in 1.6% of individuals. The cause of SUDEP is unknown but may be related to prolonged seizures, cardiac abnormalities, or brain stem dysfunction.

EEG. Early on, the EEG may be normal or exhibit focal or multifocal epileptiform activity. EEG findings tend to evolve over time, often showing moderate-to-severe background slowing and focal or multifocal sharp waves or spikes, most often in the temporal regions. Some show almost continuous delta slowing in the temporal, parietal, and occipital regions, with superimposed beta frequencies and bilateral asynchronous spikes or sharp waves [Larsen et al 2015, Denis et al 2019, Johannesen et al 2022].

Brain MRI is usually normal at the onset of seizures; however, some individuals may have MRI abnormalities including cerebral atrophy and hypoplasia of the corpus callosum. Some affected individuals have been shown to develop cerebral or cerebellar atrophy in follow-up studies [Larsen et al 2015, Singh et al 2015, Gardella et al 2018, Denis et al 2019, Kim et al 2019, Schreiber et al 2020, Hu et al 2022].

SCN8A-Related Mild-to-Moderate Developmental and Epileptic Encephalopathy (SCN8A-mild/modDEE)

SCN8A-mild/modDEE is also referred to as SCN8A-related intermediate epilepsy or SCN8A-IE.

Epilepsy. Affected individuals usually present within the first few months of life (average age of onset around five months). Seizure types include:

  • Focal seizures
  • Bilateral tonic-clonic seizures
  • Tonic seizures

Seizures are usually partially treatable using sodium channel blockers (see Treatment of Manifestations)

Intellectual disability typically ranges from mild to moderate, but most individuals have mild intellectual disability [Johannesen et al 2019]. Some individuals with intermediate epilepsy are reported to have normal cognition, but many of these individuals may be better classified as having SCN8A-related self-limited familial infantile epilepsy, as many are seizure-free on anti-seizure medication.

EEG and MRI brain findings are similar to SCN8A-DEE. Affected individuals may also exhibit movement abnormalities, most commonly hypotonia, ataxia, stereotypy, dystonia, and tremor. SUDEP has also been reported in individuals with this phenotype.

SCN8A-Related Self-Limited Familial Infantile Epilepsy (SCN8A-SeLFIE)

SCN8A-SeLFIE is also referred to as SCN8A-related benign familial infantile epilepsy or SCN8A-BFIE.

Epilepsy. Affected individuals usually present within the first year of life (average age of onset is around age 6 months). Seizures may resolve (or individuals may "outgrow seizures") [Gardella et al 2016], but many affected individuals have seizure recurrence and/or require ongoing treatment with anti-seizure medication to remain seizure-free [Anand et al 2016, Gardella et al 2016, Wang et al 2017, Schreiber et al 2020]. Seizure types include:

  • Focal seizures
  • Focal seizures evolving to bilateral tonic-clonic seizures
  • Bilateral tonic-clonic seizures

Seizures are usually treatable using sodium channel blockers (see Treatment of Manifestations.)

Cognitive development is usually normal in affected individuals.

Paroxysmal dyskinesias, triggered by stretching, motor initiation, or emotional stimuli, occurred in five of 16 individuals, with onset in puberty, including in one case series of three families with the p.Glu1483Lys pathogenic variant [Gardella et al 2016].

EEG. Initial EEG is often normal [Schreiber et al 2020], though individuals can develop focal or multifocal epileptiform abnormalities [Wang et al 2017].

Brain MRI is typically normal [Schreiber et al 2020].

SCN8A-Related Neurodevelopmental Disorder with Generalized Epilepsy (SCN8A-NDDwGE)

Epilepsy. Affected individuals usually present within the first few years of life (average age of onset is around age 42 months). Seizure types include:

  • Absence seizures
  • Generalized tonic-clonic seizures
  • Generalized myoclonic seizures
  • Febrile seizures

Seizures are usually not treatable using sodium channel blockers, which may aggravate symptoms of individuals with SCN8A loss-of-function (LOF) variants, as in this phenotype. Absence seizures may respond to typical anti-seizure medication (see Treatment of Manifestations).

Cognitive development varies. Most individuals have mild-to-moderate intellectual disability, though approximately 10% of affected individuals have severe intellectual disability.

Some individuals have language delays and behavioral issues.

SCN8A-Related Neurodevelopmental Disorder without Epilepsy (SCN8A-NDDwoE)

Individuals with this phenotype typically do not have epilepsy. However, it is important to note that developmental delay may precede seizure onset in SCN8A-DEE, SCN8A-mild/modDEE, and SCN8A-NDDwGE. Epilepsy may develop later (see median age of epilepsy onset in Table 2).

Cognitive development varies from normal to severe delays, though most individuals have moderate intellectual disability.

Other associated features reported in some affected individuals include the following:

  • Attention-deficit/hyperactivity disorder
  • Autism spectrum disorder
  • Microcephaly


It is unknown whether life span in the entire spectrum of SCN8A-related epilepsy and/or neurodevelopmental disorders is abnormal. However, in individuals with developmental and epileptic encephalopathy (DEE), early mortality is assessed to be 10.2% [Johannesen et al 2018, Johannesen et al 2022], whereas life span in other SCN8A-associated phenotypes is expected to be normal.

Since many adults with disabilities have not undergone advanced genetic testing, it is likely that adults with this condition are underrecognized and underreported.

Genotype-Phenotype Correlations

SCN8A pathogenic variants can be either gain-of-function (GoF) or loss-of-function (LoF) variants. Several genotype-phenotype correlations have been observed:

  • Affected individuals with LoF variants mostly have SCN8A-NDDwGE or SCN8A-NDDwoE, whereas affected individuals with GoF have SCN8A-DEE, SCN8A-SeLFIE, or SCN8A-mild/modDEE [Hack et al 2023]. The effectiveness of sodium channel blockers for treating epilepsy in these phenotypes is believed to be consistent with the activating effects of the SCN8A pathogenic GoF variant [Wagnon & Meisler 2015, Wagnon et al 2015a, Wagnon et al 2015b].
  • Several recurrent variants are associated with specific phenotypes (see Table 6):
    • The variants c.2549G>A (p.Arg850Gln) and c.5614C>T (p.Arg1872Trp) are associated with SCN8A-DEE.
    • The variants c.4423G>A (p.Gly1475Arg), c.4850G>A (p.Arg1617Gln), c.5615G>A (p.Arg1872Gln), and c.5630G>T (p.Asn1877Ser) are associated with SCN8A-mild/modDEE.
    • The variant c.4447G>A (p.Glu1483Lys) is associated with SCN8A-SeLFIE.
  • All individuals with GoF variants have epilepsy, whereas 50%-70% of individuals with LoF variants have epilepsy [Johannesen et al 2022, Hack et al 2023]. Based on these differences, early mortality has not been observed in individuals with LoF variants to date.


Penetrance for SCN8A-related epilepsy and/or neurodevelopmental disorders is unknown but is assumed to be complete.


Alternate naming conventions for SCN8A-related phenotypes have been used in the literature [Johannesen et al 2022]:

  • SCN8A-related mild-to-moderate developmental and epileptic encephalopathy (SCN8A-mild/modDEE) may also be described as SCN8A-related intermediate epilepsy (SCN8A-IE).
  • SCN8A-related self-limited familial infantile epilepsy (SCN8A-SeLFIE) may also be referred to as SCN8A-related benign familial infantile epilepsy (SCN8A-BFIE).


The prevalence of SCN8A-related epilepsy and/or neurodevelopmental disorders is not known.

The frequency of SCN8A pathogenic variants among individuals with DEE was around 1% (51 of 3,489) across multiple independent studies, most of which included several hundred individuals [Allen et al 2013, Carvill et al 2013, Larsen et al 2015, Mercimek-Mahmutoglu et al 2015, Møller et al 2016, Trump et al 2016, Butler et al 2017, Ko et al 2018, Kothur et al 2018, Lindy et al 2018, Balciuniene et al 2019, Costain et al 2019, Heyne et al 2019, Jang et al 2019, Lee et al 2020, Mitta et al 2020].

A study evaluating the incidence of SCN8A-related disorders in the Danish population found an estimated incidence of one in 56,247 [Johannesen et al 2022].

Differential Diagnosis

Because the phenotypic features associated with SCN8A-related epilepsy and/or neurodevelopmental disorders are not sufficient to diagnose these conditions, all genes associated with epilepsy and/or developmental delay / intellectual disability without other distinctive findings should be considered in the differential diagnosis.

See OMIM Phenotypic Series for genes associated with:


No clinical practice guidelines for SCN8A-related epilepsy and/or neurodevelopmental disorders have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with SCN8A-related epilepsy and/or neurodevelopmental disorders, the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 3.

Recommended Evaluations Following Initial Diagnosis in Individuals with SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders

Neurologic Neurologic eval
  • EEG to assess EEG background, epileptiform activity, & seizure type (when indicated)
  • Baseline brain MRI, if not performed already
Ataxia Orthopedics / physical medicine & rehab / PT & OT evalTo incl assessment of:
  • Gross motor & fine motor skills
  • Mobility, ADL, & need for adaptive devices
  • Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)
Development Developmental assessment
  • To incl motor, adaptive, cognitive, & speech-language eval
  • Eval for early intervention / special education
Neuropsychiatric evalFor persons age >12 mos: screening for behavioral concerns incl sleep disturbances, ADHD, anxiety, &/or findings suggestive of ASD
Musculoskeletal Orthopedics / physical medicine & rehab / PT & OT evalTo incl assessment of:
  • Gross motor & fine motor skills
  • Tone abnormalities
  • Mobility, ADL, & need for adaptive devices
  • Need for PT (to improve gross motor skills) &/or OT (to improve fine motor skills)
Gastroenterology / nutrition / feeding team eval
  • To incl eval of aspiration risk & nutritional status
  • Consider eval for gastrostomy tube placement in persons w/dysphagia &/or aspiration risk.
Cardiovascular Consider electrocardiogram or cardiology evalTo assess for cardiac arrhythmias, which have been identified in some persons w/variants of genes encoding other sodium channel subunits & may ↑ risk of SUDEP.
Vision Ophthalmologic evalCortical vision impairment can occur in SCN8A-DEE; assess for need for vision therapy.
Genetic counseling By genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of SCN8A-related epilepsy &/or neurodevelopmental disorders to facilitate medical & personal decision making
Family support
& resources
Assess need for:

ADHD = attention-deficit/hyperactivity disorder; ADL = activities of daily living; ASD = autism spectrum disorder; MOI = mode of inheritance; OT = occupational therapy; PT = physical therapy; SUDEP = sudden unexpected death in epilepsy


Medical geneticist, certified genetic counselor, certified advanced genetic nurse

Treatment – Targeted Therapy

Sodium channel blockers represent a targeted treatment option for SCN8A-related focal epilepsy phenotypes (SCN8A-related developmental and epileptic encephalopathy [SCN8A-DEE], SCN8A-related mild-to-moderate developmental and epileptic encephalopathy [SCN8A-mild/modDEE], and SCN8A-related self-limited familial infantile epilepsy [SCN8A-SeLFIE]) with onset in the first year of life. See Table 4.

Treatment – Supportive Care

Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see Table 4).

Table 4.

Treatment of Manifestations in Individuals with SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders

  • Standardized treatment w/ASM by experienced neurologist
  • Counsel on SUDEP risk & monitoring for seizures, particularly in persons at higher risk, incl those w/SCN8A-DEE & those w/generalized tonic-clonic seizures &/or nighttime seizures.
  • Many ASMs may be effective; studies suggest that persons w/focal epilepsy phenotypes (SCN8A-DEE, SCN8A-mild/modDEE, SCN8A-SeLFIE) respond favorably to sodium channel blockers (e.g., phenytoin, valproate, carbamazepine, lacosamide, lamotrigine, rufinamide, & oxcarbazepine). 1 Other classes of ASM may also be useful.
  • The effectiveness of sodium channel blockers is consistent w/activating effects of SCN8A pathogenic GoF variants. 2 1 study of 4 persons reported positive response to high doses of phenytoin. 3
  • Many affected persons are maintained on multiple ASMs w/incomplete seizure control. Vigorous attempts to control seizures w/drug polytherapy are warranted, as children w/DEE are at risk for SUDEP as well as prolonged acute seizures that may cause permanent injury. 4
  • Levetiracetam (Keppra®) has been reported by several families to be ineffective or occasionally assoc w/worsening seizures, encephalopathy, &/or developmental regression. 5 However, some may respond favorably, regardless of phenotype.
  • Education of parents/caregivers 6
Other treatments incl corticosteroids, immunoglobulins, vagus nerve stimulation, ketogenic diet, & cannabinoidsWhen seizures are not responsive to standard ASMs, these drugs / treatment modalities may be effective based on anecdotal data.
Developmental delay /
Intellectual disability
See Developmental Delay / Intellectual Disability Management Issues.
Poor weight gain /
Failure to thrive
  • Feeding therapy
  • Gastrostomy tube placement may be required for persistent feeding issues.
Low threshold for clinical feeding eval &/or radiographic swallowing study when showing clinical signs or symptoms of dysphagia
Constipation Eval & treatment by GI specialist
  • Eval by sleep &/or ENT specialist for any sleep issues incl sleep apnea
  • Polysomnography should be considered if obstructive or central sleep apnea is suspected.
  • Sleep deprivation & illness can exacerbate SCN8A-related seizures; thus, good sleep hygiene should be encouraged. Comorbidity w/sleep apnea can also occur frequently in persons w/epilepsy, 7 & can influence seizure control, behavior, & cognition.
  • Because of ↑ risk of SUDEP, some families use oxygen monitoring during sleep.
Aspiration pneumonia
  • Swallow eval
  • Eval by pulmonary & GI
Aspiration pneumonia occurs more commonly in SCN8A-DEE.
Respiratory insufficiency/failure Respiratory support incl respiratory therapy, supplemental oxygen, positive airway pressure, & ventilatory supportRespiratory insufficiency/failure can occur in SCN8A-DEE.
  • Ensure appropriate social work involvement to connect families w/local resources, respite, & support.
  • Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.
  • Ongoing assessment of need for palliative care involvement &/or home nursing
  • Consider involvement in adaptive sports or Special Olympics.

ASM = anti-seizure medication; GoF = gain of function; SCN8A-DEE = SCN8A-related developmental and epileptic encephalopathy; SCN8A-mild/modDEE = SCN8A-related mild-to-moderate developmental and epileptic encephalopathy; SCN8A-SeLFIE = SCN8A-related self-limited familial infantile epilepsy; SUDEP = sudden unexpected death in epilepsy


Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy Foundation Toolbox.


Developmental Delay / Intellectual Disability Management Issues

The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.

Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.

Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan (IEP) is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition. Developmental preschool is center based; for children too medically unstable to attend, home-based services are provided.

All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:

  • IEP services:
    • An IEP provides specially designed instruction and related services to children who qualify.
    • IEP services will be reviewed annually to determine whether any changes are needed.
    • Special education law requires that children participating in an IEP be in the least restrictive environment feasible at school and included in general education as much as possible, when and where appropriate.
    • Vision and hearing consultants should be a part of the child's IEP team to support access to academic material.
    • PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.
    • As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.
  • A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.
  • Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.
  • Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.

Motor Dysfunction

Gross motor dysfunction

  • Physical therapy is recommended to maximize mobility and to reduce the risk for later-onset orthopedic complications (e.g., contractures, scoliosis, hip dislocation).
  • Consider use of durable medical equipment and positioning devices as needed (e.g., wheelchairs, walkers, bath chairs, orthotics, adaptive strollers).
  • For muscle tone abnormalities including hypertonia or dystonia, consider involving appropriate specialists to aid in management of baclofen, tizanidine, Botox®, anti-parkinsonian medications, or orthopedic procedures.

Fine motor dysfunction. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.

Oral motor dysfunction should be assessed at each visit and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) is recommended to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.

Communication issues. Consider evaluation for alternative means of communication (e.g., augmentative and alternative communication [AAC]) for individuals who have expressive language difficulties. An AAC evaluation can be completed by a speech-language pathologist who has expertise in the area. The evaluation will consider cognitive abilities and sensory impairments to determine the most appropriate form of communication. AAC devices can range from low-tech, such as picture exchange communication, to high-tech, such as voice-generating devices. Contrary to popular belief, AAC devices do not hinder verbal development of speech, but rather support optimal speech and language development.

Neurobehavioral/Psychiatric Concerns

Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst.

Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.

Concerns about serious aggressive or destructive behavior can be addressed by a pediatric psychiatrist.


To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in Table 5 are recommended.

Table 5.

Recommended Surveillance for Individuals with SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders

  • Monitor seizures as clinically indicated.
  • Assess for new manifestations such as seizures, changes in tone, & movement disorders.
At each visit
Sleep Assess for any sleep issues / sleep apnea.
  • Query for factors that ↑ SUDEP risk, incl generalized tonic-clonic seizures & nighttime seizures.
  • Assess seizure monitoring strategies.
Development Monitor developmental progress & educational needs.
Behavioral assessment for anxiety, attention, & aggressive or self-injurious behavior
Musculoskeletal Physical medicine, OT/PT assessment of mobility, self-help skills
Family/Community Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).

OT = occupational therapy; PT = physical therapy; SUDEP = sudden unexpected death in epilepsy

Agents/Circumstances to Avoid

Several families of affected individuals report worsening of seizures, encephalopathy, and/or developmental regression with levetiracetam (Keppra®) [Schreiber et al 2020]. However, some may respond favorably to levetiracetam, regardless of the phenotype. Therefore, careful evaluation and follow up by a neurologist is recommended.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

NBI-921352, an Nav1.6 selective sodium channel inhibitor, is currently in Phase II clinical trials for individuals with SCN8A-related developmental and epileptic encephalopathy (SCN8A-DEE) (NCT04873869) [Johnson et al 2022].

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

SCN8A-related epilepsy and/or neurodevelopmental disorders are inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

  • Some individuals diagnosed with an SCN8A-related phenotype have the disorder as the result of a de novo SCN8A pathogenic variant. Individuals with more severe SCN8A-related phenotypes are more likely to have the disorder as the result of a de novo pathogenic variant than individuals with milder SCN8A-related phenotypes.
  • Some individuals diagnosed with an SCN8A-related phenotype have the disorder as the result of a pathogenic variant inherited from an affected and/or mosaic parent. Of families in which parental testing was performed, the percentage of individuals with a pathogenic variant inherited from a mosaic and/or affected parent varied by phenotype [Johannesen et al 2022]:
    • 2% (3/166) of individuals with SCN8A-related developmental and epileptic encephalopathy (DEE)
    • 10% (3/29) of individuals with SCN8A-related mild-to-moderate DEE (also referred to as intermediate epilepsy)
    • 47% (7/15) of individuals with SCN8A-related self-limited familial infantile epilepsy (also referred to as benign familial infantile epilepsy)
    • 33% (5/15) of individuals with SCN8A-related neurodevelopmental disorder (NDD) with generalized epilepsy
    • 60% (9/15) of individuals with SCN8A-related NDD without epilepsy
  • If the proband appears to be the only affected family member (i.e., a simplex case), molecular genetic testing is recommended for the parents of the proband to confirm their genetic status and to allow reliable recurrence risk counseling.
  • If the pathogenic variant identified in the proband is not identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:
  • The family history of some individuals diagnosed with an SCN8A-related phenotype may appear to be negative because of failure to recognize the disorder in family members or reduced penetrance. Therefore, an apparently negative family history cannot be confirmed unless molecular genetic testing has demonstrated that neither parent is heterozygous for the pathogenic variant identified in the proband.

Sibs of a proband. The risk to the sibs of the proband depends on the clinical/genetic status of the proband's parents:

Offspring of a proband. Each child of an individual with an SCN8A-related phenotype has a 50% chance of inheriting the SCN8A pathogenic variant.

Other family members. The risk to other family members depends on the genetic status of the proband's parents: if a parent has the SCN8A pathogenic variant, the parent's family members may be at risk.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to parents of affected individuals.

Prenatal Testing and Preimplantation Genetic Testing

Once the SCN8A pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders: Genes and Databases

GeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
SCN8A 12q13​.13 Sodium channel protein type 8 subunit alpha SCN8A @ LOVD SCN8A SCN8A

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders (View All in OMIM)


Molecular Pathogenesis

SCN8A encodes the sodium channel protein type 8 subunit alpha (isoform Nav1.6), one of four voltage-gated sodium channels expressed in the human brain and predominantly expressed in excitatory as well as inhibitory neurons. The protein includes four homologous domains with six transmembrane segments each, as well as two large cytoplasmic loops, a short cytoplasmic inactivation gate, and cytoplasmic N-terminal and C-terminal domains (see Figure 1, with exon designations and functional domains marked). The amino acids forming the sodium-specific pore are located in segments S5 and S6 of each domain. The protein is highly conserved through evolution, and the human sequence can be aligned with the bacterial sodium channel, whose crystal structure has been determined.

Figure 1. . Intron-exon organization of SCN8A.

Figure 1.

Intron-exon organization of SCN8A. Horizontal bars mark the positions of the introns of the sodium channel protein type 8 subunit alpha (Nav1.6) superimposed on the secondary structure of the sodium channel. Adapted from Plummer et al [1998]

Most pathogenic variants associated with SCN8A-related epilepsy and/or neurodevelopmental disorders result in substitution of a single amino acid (see Figure 2 for a distribution of missense variants). Of the nine pathogenic variants tested functionally, seven resulted in elevated channel activity due to premature channel opening or impaired channel closing. Elevated activity of Nav1.6 leads to neuronal hyperexcitability and seizures in a mouse model of SCN8A-related epilepsy with encephalopathy [Wagnon et al 2015b]. Nav1.6 is expressed at a low level in cardiac ventricular myocytes, and cardiac arrhythmia is seen in the mouse model, suggesting that sudden unexplained death in epilepsy may have a cardiac component [Frasier et al 2016].

Figure 2. . Positions of SCN8A missense pathogenic variants in the sodium channel protein type 8 subunit alpha (Nav1.

Figure 2.

Positions of SCN8A missense pathogenic variants in the sodium channel protein type 8 subunit alpha (Nav1.6). The protein has four homologous domains (DI to DIV), each containing six transmembrane segments (S1-S6). Data from www.scn8a.net

Mechanism of disease causation

  • Gain of function in SCN8A-related developmental and epileptic encephalopathy (DEE), SCN8A-related mild-to-moderate DEE, and SCN8A-related self-limited familial infantile epilepsy
  • Loss of function in SCN8A-related neurodevelopmental disorder with generalized epilepsy and SCN8A-related neurodevelopmental disorder without epilepsy

SCN8A-specific laboratory technical considerations

  • SCN8A includes 26 coding exons. The approximate position of each exon is indicated in Figure 1. During the first year of postnatal life, the "neonatal" and the "adult" exons are expressed in roughly equal proportions [O'Brien et al 2012].
  • There are several alternatively spliced exons: 6A (adult) and 6N (neonatal) that encode segment 3/4 of domain I, as well as alternatively spliced exons 21A and 21N that encode segment 3/4 of domain III.
  • Exon 21N is a "poison" exon that contains an in-frame stop codon and encodes a truncated protein terminating in domain III that does not have channel activity. Therefore, the reference sequence for missing exon 21 should not be used for sequence comparisons: NM_001177984.2 (ENST00000545061).
  • The most complete full-length reference transcript contains exon 6N and exon 21A: NM_014191.3 (ENST00000354534).

Table 6.

Highly Recurrent SCN8A Pathogenic Gain-of-Function Variants 1

Reference SequencesDNA Nucleotide ChangePredicted Protein ChangeAssociated Phenotype

SCN8A-DEE = SCN8A-related developmental and epileptic encephalopathy; SCN8A-mild/modDEE = SCN8A-related mild-to-moderate developmental and epileptic encephalopathy; SCN8A-SeLFIE = SCN8A-related self-limited familial infantile epilepsy

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.


Variants known to be present in >15 individuals

Chapter Notes

Author Notes

Michael F Hammer, PhD (moc.liamg@ofni.a8ncs), is actively involved in clinical research regarding individuals with SCN8A-related epilepsy and related disorders. He would be happy to communicate with persons who have any questions regarding diagnosis of SCN8A-related epilepsy and/or neurodevelopmental disorders or other considerations.

John M Schreiber, MD, is actively involved in treating patients with SCN8A-related epilepsy and related disorders and is also interested in hearing from clinicians treating families affected by this disorder or in whom no causative variant has been identified through molecular genetic testing.

Contact Michael F Hammer (moc.liamg@ofni.a8ncs) to inquire about review of SCN8A variants of uncertain significance.

The Hammer lab identified the first case of SCN8A-related epilepsy and has established a registry and an online database of the clinical features of patients with pathogenic variants in SCN8A (www.scn8a.net). The Hammer lab is also performing experiments using mouse models of SCN8A-related epilepsy and/or neurodevelopmental disorders.


We thank Wishes for Elliott (www.wishesforelliott.com) for funding the first SCN8A workshop in association with an American Academy of Neurology meeting in Washington, DC (April 20, 2015).

Author History

Michael F Hammer, PhD (2016-present)
Heather C Mefford, MD, PhD; St Jude Children's Research Hospital (2016-2023)
Miriam H Meisler, PhD; University of Michigan (2016-2023)
John M Schreiber, MD (2023-present)
Jacy L Wagnon, PhD; University of Michigan (2016-2023)
Maya Xia, BA (2023-present)

Revision History

  • 6 April 2023 (gm) Comprehensive updated posted live
  • 25 August 2016 (bp) Review posted live
  • 29 September 2015 (mfh) Original submission


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