What are the other Names for this Condition? (Also known as/Synonyms)

• Early Infantile Epileptic Encephalopathy-13 (EIEE13)
• EIEE13 (Early Infantile Epileptic Encephalopathy)
• SCN8A Epilepsy

What is SCN8A Encephalopathy? (Definition/Background Information)

• SCN8A Encephalopathy is a very rare form of early-onset epilepsy that causes multiple types of seizures and developmental delay or regression (loss of skills)
• Seizures begin during the first 18 months of life, at an average age of 4 months. Types of seizures may include generalized tonic-clonic seizures, infantile spasms, absence seizures, and focal seizures
• Other signs and symptoms of SCN8A Encephalopathy may include low muscle tone (hypotonia), a high pain tolerance, movement disorders (such as dystonia and ataxia), mild to severe intellectual disability, sleep problems, and autistic-like features
• In some people with SCN8A Encephalopathy, various other medical problems have been reported including hearing or vision problems, scoliosis, and difficulty regulating body temperature
• About 10% of people with SCN8A Encephalopathy reported in the literature have died from sudden unexpected death in epilepsy (SUDEP)
• SCN8A Encephalopathy is caused by mutations in the SCN8A gene. Inheritance is autosomal dominant, but most people with SCN8A Encephalopathy have a new mutation in the gene that was not inherited from a parent
• Treatment aims to control seizures with medications, which is extremely challenging. Seizure control should be managed by a pediatric neurologist with expertise in epilepsy who is familiar with SCN8A Encephalopathy

(Source: SCN8A Encephalopathy; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets SCN8A Encephalopathy? (Age and Sex Distribution)

• SCN8A Encephalopathy is a very rare congenital disorder. Approximately, 140 cases have been reported in the medical literature
• This condition accounts for about 1% of all cases of epilepsy with encephalopathy
• The onset of symptoms occurs within 18 months of birth
• Both males and females may be affected by this condition
• Worldwide, individuals of all races and ethnicities may be affected

What are the Risk Factors for SCN8A Encephalopathy? (Predisposing Factors)

• A positive family history may be an important risk factor, since SCN8A Encephalopathy can be inherited
• Currently, no risk other factors have been clearly identified for SCN8A Encephalopathy

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of SCN8A Encephalopathy? (Etiology)

• SCN8A Encephalopathy is caused by mutation(s) in the SCN8A gene
• The protein coded by this gene is part of a sodium ion channel, which plays a crucial role in the communication between neurons via electrical signals
• A mutation in this gene causes the sodium ion channel to remain open continuously, causing increases neuronal activity. This results in the signs and symptoms characteristic to this disorder
• In most cases, causative mutations in SCN8A occur sporadically, during the formation of the egg or sperm
• However, the condition can run in families, and is inherited in an autosomal dominant manner

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of SCN8A Encephalopathy?

The signs and symptoms of SCN8A Encephalopathy may include:

• Autism
• Developmental regression
• Epileptic encephalopathy
• Epileptic spasms
• Generalized hypotonia
• Global developmental delay
• Intellectual disability
• Progressive microcephaly
• Cerebral atrophy

(Source: SCN8A Encephalopathy; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is SCN8A Encephalopathy Diagnosed?

SCN8A Encephalopathy is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative SCN8A gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of SCN8A Encephalopathy?

The complications of SCN8A Encephalopathy may include:

• Severe intellectual disability
• Poor intentional muscle movement
• Epilepsy that is hard to control
• Behavioral problems
• Poor quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is SCN8A Encephalopathy Treated?

There is no cure for ASCN8A Encephalopathy, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. Treatment methods may include medication to control episodes of epilepsy.

How can SCN8A Encephalopathy be Prevented?

SCN8A Encephalopathy may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of SCN8A Encephalopathy? (Outcomes/Resolutions)

• The prognosis of SCN8A Encephalopathy is dependent upon the severity of the signs and symptoms and associated complications, if any
• Hard-to-treat seizures and a compromised ability for intentional movement (in about 50% of affected individuals) may lead to a poor quality of life
• In rare cases, sudden unexpected death in epilepsy (SUDEP) is known to occur

Additional and Relevant Useful Information for SCN8A Encephalopathy:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/