Get To Know The Cute Syndrome Foundation (SCN8A Epilepsy)
Updated: Oct 4
SCN8A Epilepsy is a rare developmental epileptic encephalopathy associated with mutations in the gene SCN8A. The first known case of SCN8A Epilepsy was discovered in 2011 by Michael Hammer. Since then, ~450 patients have been diagnosed with SCN8A epilepsy. Problematic variants in SCN8A are very rare and most commonly sporadic, not inherited. The Danish Epilepsy Center Filadelfia estimates the frequency of SCN8A mutations at 1/56,247 (unpublished manuscript). Since 2011 we know of 25 individuals between the ages of 28 days and 26 years who have died as a result of complications related to their SCN8A mutations. Epilepsy is a hallmark of this disorder, with the majority of patients experiencing seizures early in life, with an average seizure onset at 4 months of age (Schreiber JM, Tochen L, Brown M, et al. A multi-disciplinary clinic for SCN8A- related epilepsy). However, 5% of patients with pathogenic SCN8A mutations never experience seizures (Encinas AC, Moore IKM, Watkins JC, Hammer MF. Influence of age at seizure onset on the acquisition of neurodevelopmental skills in an SCN8A cohort).
SCN8A Clinical Features
As is the case among many rare epilepsies, SCN8A is not only about seizures. A recent survey of 125 patients, conducted by The Cute Syndrome Foundation in conjunction with Xenon Pharmaceuticals, reinforces this. More than 90% of respondents present with seizures. Just over 40% have movement disorders, slightly less that 60% exhibit hypotonia, and over 70% have intellectual disability. Nearly half of respondents have swallowing problems and G-Tubes. And approximately a quarter of the population presents with Autism; nearly the same percent have visual impairment (Grayson C, Cutts A, Luzon C, Butterfield N, Savoie H. An online survey of caregivers of patients with SCN8A-Related Epilepsy). 65% of our population does not have seizure freedom. All epilepsy subgroups exhibit better seizure control with sodium channel blockers, and may require very high doses to achieve seizure control. (Encinas AC, Moore IKM, Watkins JC, Hammer MF. Influence of age at seizure onset on the acquisition of neurodevelopmental skills in an SCN8A cohort). For many individuals with SCN8A Epilepsy, Keppra (Levetiracetam) is associated with clinical worsening or regression (Schreiber JM, Tochen L, Brown M, et al. A multi-disciplinary clinic for SCN8A- related epilepsy).
There is, however, a lot of heterogeneity within the community. Children with SCN8A can present very differently one from the other. Some children have serious developmental limitations such as a lack of head control, no language development, and feeding challenges requiring feeding tubes. While a number of children with SCN8A do walk and talk, they may also experience delays as well as behavioral, sensory, and motor planning challenges. Other children struggle with repeat infections, respiratory challenges, movement disorders, and a number of other health challenges. Additionally, due to the frequently high dosages of multiple AEDs, the population is plagued by high rates of medication side-effects.
Get to Know The Cute Syndrome Foundation
The Cute Syndrome Foundation’s mission is to raise awareness of SCN8A mutations, fund the dedicated and talented scientists researching SCN8A, and support the families around the world who are affected by this disorder. Our organization is run by 30 volunteer family members, and we are actively in touch with over 300 families of children with SCN8A mutations.160 of these families are located in the US, across 38 states. Since our reach is international, we work closely with international SCN8A advocates and their independent organizations (established and evolving) in order to ensure consistency, collaboration, and alignment in family outreach, research priorities, and successful interfacing with industry. While our international partners run their local priorities, fundraising, and legalities, all of these leaders also act as TCSF volunteers to further integrate our combined efforts. The Cute Syndrome Foundation was founded in 2013 and has focused exclusively on SCN8A since 2015. The SCN8A Facebook support group was established by Juliann Bradish, PharmD in 2014, who joined The Cute Syndrome Foundation volunteer team in 2015, allowing The Cute Syndrome Foundation and the support group to merge efforts.
I am especially proud of ...
While small, our community is highly active and engaged. Since 2015 we have held an annual SCN8A Researcher, Clinician, and Family Gathering in which our families engage directly with the scientific leaders in the field, as partners and fellow experts. TCSF sees our role as creating platforms in which patient/caregiver knowledge can be shared, encouraging collaborations that actively include the patient voice, and educating our family population so that they can be more informed participants. At our annual Gathering in 2019 we welcomed over 80 family members, including 15 children with SCN8A. Our families are the daily on-the-ground experts in SCN8A, and the most effective advancements will be made not only with our consent, but with our fundamental engagement.
In anticipation of upcoming clinical trials, this fall The Cute Syndrome Foundation is very proud to be expanding our family education programming by launching a Clinical Trial Readiness Educational Series. We believe that helping educate our families about drug discovery and clinical trials is essential to having an informed community that can consent to participate in studies. In September of this year, we will launch an educational series to engage the SCN8A families in important discussions surrounding drug discovery and clinical trials.
Excited to REN because...
We are excited to work collaboratively with other REN advocates in order to leverage our collective voices in order to improve outcomes for rare epilepsy patients. We are especially interested in projects that work to improve preparation for and the quality of clinical trials for rare epilepsies through collaborations with diverse stakeholders. We are excited about REN’s ability to help the rare epilepsy world tackle complex problems that we cannot solve alone!
My journey and motivation...
The Cute Syndrome was a term initially coined to describe the suite of symptoms that my daughter Esmé had since birth—many of which have significant overlap with those associated with SCN8A Epilepsy. Esmé’s medical complexities are now presumed to be caused by as many as four separate genetic mutations. However, the causal relationship between any of these mutations and her symptoms remains a mystery—so, in many ways, she is functionally undiagnosed.
The “Cute Syndrome” is a term that the SCN8A community lovingly embraced, and so it has evolved into something more than just Esmé’s condition. And Esmé is happy to share it with this exceptional community, just as I am thrilled to have the honor to work with this community.
However, Esmé’s diagnostic complexity keeps me thinking about the commonalities across diagnoses in the rare epilepsy space. And it was in this spirit that I volunteered to work on the REN transition team in 2019 and the coordinating counsel in 2020—because I am eager to help the larger community of Rares go further, faster, together—for all of our children.
By Hillary Savoie, PhD, Founder/Director The Cute Syndrome Foundation