Clinical Features, also known as comorbidities or non-seizure outcomes are distinct for each SCN8A phenotype. Below is information about how clinical features were identified for inclusion, consensus findings on the frequency, severity and likely change over time for each phenotype and definitions of severity.
SCN8A Related
Health Conditions
In this video, Dr. Christelle Achkar highlights key findings from the SCN8A Alliance’s consensus on clinical features of SCN8A-related disorders. This overview serves as an introduction to the in-depth resources and comprehensive guidelines available on our website, emphasizing the importance of recognizing the wide spectrum of SCN8A phenotypes. For a deeper exploration of these insights and more, delve into our extensive collection of materials designed to support families and clinicians navigating SCN8A.
These plots show what percent of participants in the consensus agreed that each of these 5 features was likely to be present in each phenotype. For example, all participants thought that speech, fine motor skills, intellectual disabilities, sleep disturbances were present in those with Severe DEE.
Presence of 5 Common Clinical Features for Each Phenotype
These radar plots show the presence of five clinical features, which play a significant role in the expression of neurodevelopmental disorders. These features—Speech, Fine Motor Skills, Intellectual Disabilities, Behavioral Challenges, and Sleep Disturbances—are key indicators that vary in prevalence across the 5 phenotypes: Severe DEE, Mild/Moderate DEE, SeL(F)IE, NDD w/ Epilepsy, and NDD w/o Epilepsy.
How Clinical Features were identified for inclusion
This table illustrates steps in determining which clinical features would be included in the study. Initially, the Comorbidities and Prognosis workgroup, building on the literature and with input from caregivers in the Core Panel, identified 19 initial possible comorbidities associated with SCN8A-related disorders. In Round one, the Review Panel was asked to identify how commonly these 19 comorbidities present across the phenotypes (>50% of the time, around 50% of the time, <50% of the time). Respondents were asked to comment on additional comorbidities that should be queried in subsequent rounds.
Seven clinical features were dropped from further inquiry as more than a majority of respondents did not believe they occurred over 50% of the time. These included neurogenic bladder, ADHA, Pyramidal signs, cardiac, ENT, Endocrine and Urology issues. Respondents proposed adding autonomic, sleep disturbances, and orthopedic issues. Two were added to clarify relationships to other areas – emotional dysregulation was added to distinguish from behavioral issues and feeding was split out from overall GI issues.
Frequency, Severity, and change over time of Clinical Features by Phenotype
More detailed information for each phenotype can be found on our SCN8A phenotypes page. Each table lists all 17 included comorbidities, the anticipated severity level for each DEE, and expected change over time. The first table shows severe DEE, and each table below displays the same information but in relation to severe DEE, as seen in the legend on top.
Severe DEE
Mild/Moderate
NDD with Generalized Epilepsy
NDD without Generalized Epilepsy
SeL(F)IE
Definitions of Comorbidities and Severity Levels
Table info
Definitions of Comorbidity Changes Over Time
Supplemental Resources: Clinical Features by Gain of Function and Loss of Function
These two charts shows how clinical features vary between loss of function and gain of function variants.
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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.
Disclaimer for Consensus and Individual Variation
This consensus process was carried out by a panel of expert clinicians who actively treat patients with SCN8A-related disorders. Guidelines determined from a consensus differ from those determined from a population-based study*. The extent of consensus reached is restricted by the number of patients seen by each clinician and the portion of the disease spectrum these patients represent.
Consensus guidelines serve as a recommended starting point for clinicians to treat patients based on the best evidence available. If an affected individual does not fit the expected profile, it is important to reassess your treatment plan and revise accordingly. Reassessment of the consensus guidelines will occur as new data become available and the number of patients seen by clinicians increases.
Guidelines based on future consensus processes will therefore reflect advancements in clinical care.
*Population-based studies reveal general trends for large subsets of the population. It is important to remember that each individual is unique and may not necessarily follow these trends regarding developmental progression, seizure remission, or effective treatment.