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Below, we highlight findings from the consensus about the significance of early diagnosis, patterns of EEGs and MRIs and critical areas of counseling families should receive at diagnosis.

SCN8A Diagnosis

Discover the essential role of early diagnosis in SCN8A-related disorders with insights from Dr. Mitsuhiro Kato, an expert in pediatric neurology. This brief yet informative video presentation underscores the consensus on the vital importance of genetic testing for improving outcomes in SCN8A epilepsy. Learn about the significance of early and precise identification through genetic panels or whole exome sequencing, setting the stage for the comprehensive resources and guidelines available below.

Play Video

Key Points:

  • Early diagnosis of SCN8A is important to inform treatment and may improve long-term seizure outcomes.
  • The function of an SCN8A variant (gain-of-function or loss-of-function) is important for informing treatment and anticipating phenotypes.
  • Recognizing the wide range of clinical presentations is essential for accurate diagnosis and treatment planning.
Genetic Testing

Types of genetic testing recommended:

  • Epilepsy gene panels
  • Whole exome sequencing
  • Whole genome sequencing can be insightful in cases of drug-resistant epilepsy or neurodevelopmental disorders without a clear cause.

Familial Testing

  • All cases with new SCN8A variants should have parental testing conducted.
  • Families newly diagnosed with SCN8A should receive genetic counseling.
Referrals

There was moderate to strong consensus for each treatment item listed below. There are 4 treatment options that caregivers were not provided and therefore only clinician consensus is reported. There was 100% consensus on 3 items, SeL(F)IE first line treatments, sodium channel blockers for GOF variants in SCN8A, and seizure freedom among SCN8A LOF variants.

Legend:

The purple bar represents the consensus level among caregivers.
The orange bar represents the consensus level among clinicians.
Moderate Consensus: The first dashed line represents that at least 80% of respondents fully or partially agree, and fewer than 10% disagree.
Strong Consensus: The second dashed line represents when 80% or more of respondents fully agree.

Need for seizure emergency plan and rescue medications

Need for seizure emergency plan and rescue medications

Potential for drug-resistant epilepsy balancing seizure control  and quality of life

Potential for drug-resistant epilepsy balancing seizure control  and quality of life

Wide spectrum of severity

Wide spectrum of severity

Varying prognosis within and across phenotypes

Varying prognosis within and across phenotypes

Risk of sudden unexpected death in epilepsy (SUDEP)

Risk of sudden unexpected death in epilepsy (SUDEP)

Expected presence and evolution of comorbidities.

Expected presence and evolution of comorbidities.

Understanding seizure types and possible triggers. 

Understanding seizure types and possible triggers. 

Risks and benefits of recommended treatments

Risks and benefits of recommended treatments

Prognosis, as requested

Prognosis, as requested

Suggested Counseling at Diagnosis

Types of genetic testing recommended:

  • Epilepsy gene panels
  • Whole exome sequencing
  • Whole genome sequencing can be insightful in cases of drug-resistant epilepsy or neurodevelopmental disorders without a clear cause.

Familial Testing

  • All cases with new SCN8A variants should have parental testing conducted.
  • Families newly diagnosed with SCN8A should receive genetic counseling.

To test for SCN8A and its variants, genetic testing is recommended, including:

  • Epilepsy gene panels
  • Exome sequencing
  • Whole genome sequencing can be insightful in cases of drug-resistant epilepsy or neurodevelopmental disorders without a clear cause.

To test for function type, loss-of-function (LOF) or gain-of-function (GOF), a breakthrough predictive model using clinical features is being used with over 90% accuracy. Five key clinical features were identified as predictive:

  1. The development of seizures?
  2. Age at seizure onset?
  3. Seizure types?
  4. Intellectual and developmental disability (IDD)?
  5. Mutation type?

To find out more come to any SCN8A Family meeting in our events calendar and talk to Dr. Hammer yourself.

  • Early diagnosis of all SCN8A-related disorders, including SCN8A DEE, improves both short term and long term outcomes and the early use of sodium channel blockers can improve long-term seizure outcomes.
  • The function of an SCN8A variant, gain-of-function or loss-of-function, is important for informing treatment and anticipating phenotypes.
  • Recognizing the wide range of clinical presentations is essential for accurate diagnosis and treatment planning.
  • Families should be counseled by a geneticist on areas such as mosaicism, to see if the variant is present in only a portion of a parent’s cells, which can impact recurrence risk for future children.
  • Understanding if a variant is inherited or de novo (occurring for the first time in the child) can help inform potential recurrence risk and prognosis.
  • Cases with new SCN8A variants should consider parental testing to determine if the variant is inherited.
  • Understanding if a variant is inherited or de novo (occurring for the first time in the child) can help inform potential recurrence risk and prognosis.

The implications from the parental testing recommendations are important and inform testing on siblings:

    • Inherited Variant: If a parent carries the SCN8A variant, there’s a potential recurrence risk for siblings. Genetic counseling and testing may be recommended for siblings in this situation.
    • De Novo Variant: If the SCN8A variant arose in the child for the first time, the risk to siblings is generally considered low, but not absolutely zero (due to the possibility of undetectable parental mosaicism).
SCN8A Research

For Clinicians & Researchers

We are excited about collaboration. If you are interested in collaborating around SCN8A patient care and /or research for SCN8A-releated disorders, PLEASE let us know. We want to hear from you. Currently we work with over a dozen labs and leading SCN8A clinicians to advance the science of SCN8A.

Learn about the work of the Invitation only SCN8A Research Consortium meeting quarterly to share updates on ongoing work, share assets, and develop new collaborative projects [not sure if we’d open up an application process??]

Learn about the International SCN8A Registry, highlights of what’s been learned and how to collaborate/get access to registry data for planned research projects

Follow the public Facebook group where updates on our programs, research, and new findings from the SCN8A Registry are shared

Learn more about the Alliance’s Global Research Strategy and efforts to accelerate progress toward better treatments and outcomes – and how I might get involved

Be added to the periodic SCN8A Newsletter


– Keep Exploring –

IMPORTANT: While this consensus data provides new and valuable insights about best practices in the diagnosis and treatment of SCN8A, this is not medical advice. It can inform clinicians and caregivers alike in developing optimal treatment plans for each individual.