Welcome SCN8A Families

 

Sodium ChaNnel, voltage gated,
type VIII, Alpha subunit

 

Sodium channel, voltage gated, type VIII, alpha subunit also known as SCN8A or Nav1.6 is a protein which in humans is encoded by the SCN8A gene. It is a voltage-gated sodium channel.

PDB rendering based on 1byy. Source: Wikipedia

Welcome to Wishes for Elliott where our mission is to advance the state of knowledge on SCN8A mutations in order to accelerate the pace of science in providing answers and help for our children. We also are committed to helping families connect with a range of ongoing efforts to make personal connections, support vital data collection efforts, and other useful resources.

 

One of our most frightening days – just back in May, 2014 - was when we learned of Elliott’s specific mutation and tried to google it for more information – we were awestruck with the results: 

We have come a long way since then – and an entire community of networks – families and professionals is taking shape.

While we are sorry others are struggling with the debilitating effects of the SCN8A mutation, we are so glad you found us. One of our more personal hopes in organizing Wishes for Elliott was that we would connect with other families sharing similar struggles, helping us break through the profound isolation and despair that can so easily take over.

Our primary focus since starting Wishes for Elliott in April 2014, has been on raising enough funds to accelerate the pace of research on SCN8A by hosting the first scientific conference of researchers and clinicians working with SCN8A. With the incredible donations we recieved and intense planning with our Children's National team, the first gathering of SCN8A experts took place in April 2015. We are now increasing our efforts to reach out and expand the base of support for ground-breaking research opportunities as identified by the resulting collaboration of experts. We also want to help play a role as a resource to help other SCN8A families connect with the growing community of families and important efforts to collect essential data on all SCN8A children.

 

We hope by sharing this information and expanding the network of SCN8A families, that our community broadens to work together to continue to accelerate the pace of getting answers and hope for our children.

 

There are three different categories of information below:

 

Frequently Asked Questions about SCN8A

How/Where to Get Help AND Accelerate Progress

Resources

 

Frequently Asked Questions about SCN8A

 

PLEASE NOTE: These are largely very basic efforts to explain what is far more complex and nuanced than we really understand. Thankfully, far more rigorous and still readable sources are listed below and under development. We will provide links and update this information as new sources come online.

 

What is SCN8A? SCN8A is a form of epilepsy, which despite being one of the oldest-known and common neurological diseases, remains  poorly understood. The most prevalent symptom of all epilepsies is seizures, which occur when the normal pattern of electrical currents through the brain are interrupted by sudden and unusually intense bursts of electrical energy.

 

The SCN8A gene regulates the flow of sodium related to the functioning of neurons and muscle and are responsible for the “rising phase of the action potential.” 

 

The SCN8A gene was isolated in mice in 1995 and identified in humans in 2012 – so understanding of the function and how SCN8A mutations affect various individuals is still in an early stage.

 

While learning your child has an SCN8A mutation is certainly a step forward in the potential for finding answers, it is sadly just the beginning. Yet this knowledge allows you to become part of the wonderful community of parents caring for affected children. It also allows you to become part of the solution – by supporting and participating in active research efforts to unravel the many mysteries of how this mutation functions. This is where the hope lies in moving toward better treatment and eventual cures for the often debilitating effects of SCN8A mutations.

 

How does SCN8A affect children? Children who are affected have seizure onset generally between birth (or even during pregnancy) and 18 months of age. While impacts vary, most children also have developmental and cognitive disabilities and movement disorders. There are also frequent language delays and many of the children are largely non-verbal. For example, Elliott, who is among the children most severely affected, has never had neck control, voluntary control of any muscles and cannot sit, roll grasp or eat through his mouth due to the inability to protect his airway. Wile he makes sounds, he has no language and has severe vision impairment. How much or little of his condition is specially cause by the SCN8A mutation alone remains an open question.

 

One blessing but concern is that many of these children appear to have an extremely high tolerance for pain. While it’s wonderful that they can tolerate much of the pain and discomfort associated with the disorder – it requires that we as parents be very observant and mindful of possible problems. This is another area why trusting your own instincts is so important – you will know things about your child that could be very important – but that no one also will pick up on.

 

Finally, there is something extraordinarily special about all our children. In general, many of them are happy children who despite often pervasive and profound limitations are incredibly sweet and responsive, albeit in small ways.

 

Be sure to enjoy our carousel of the “faces of SCN8A” children on our home page – they are each so beautiful and special.

 

Here are some pictures of Elliott’s joy coming through in the midst of some difficult times.

 

Last feeding therapy before food by mouth stopped due to aspiration risk

Celebrating Grandpa’s 70th birthday in the ICU!

Fun with Grandma during long hospital stay

Chatting with Bubbie during intense hospital stay with out of control seizures

Ever smiling through everything

Intubated after another case of pneumonia and septic shock.

What is the incidence of SCN8A cases? While only about 90 cases have been documented so far worldwide, research indicates that SCN8A mutations could account for roughly 1 percent of epilepsies in young children. As such, the number of identified cases is expected to grow rapidly. And as the numbers grow, so does our potential to gather essential data to fuel the needed research to bring real answers to all our questions and hopes.

 

What is the prognosis for children with SCN8A? This is largely unknown although in our small family group of about 40+ children, there are several pre-teen and teen-aged children. There is only one confirmed case of an adult with an SCN8A mutation who has controlled seizures and some intellectual disabilities. Yet with the cause of nearly 2/3 of epilepsies unknown, based on tests and information used as recently as three years ago which excluded SCN8A, there is reason to believe there may be older children and adults with SCN8A mutations. Sadly though, SCN8A has been linked to a high incidence of sudden death (SUDEP), so it is unclear what the overall prognosis is and why some children succumb.

 

Are treatments available? Yes and no. There are many anti-epileptic drugs (AEDs) which can and do help children with SCN8A get some control of seizures. In our own recent survey gathering information on 20 of our children, we found wide variation in the level of seizure control:

 

Level of Seizure control

  • Little (multiple daily)                  20.0%

  • Some (not daily)                       40.0%

  • Good (infrequent)                     30.0%

  • Very Good (very infrequent)     10.0%

 

 

While it is clear a large number of kids do not yet have seizure control, there is also the sad reality that far too little is known about conditions and characteristics of our children and what is likely to make specific drugs either effective or highly toxic. We already know that there is a wide variation in which AEDS work or harm different children with SCN8A mutations – in some cases the same medication can be highly effective in controlling seizures in one child while for another is is highly toxic or just doesn't work.

 

The ketogenic diet and CBDs (or cannaboids oils) have also frequently been prescribed – again with uneven results.

 

Clearly, research into better understanding when and which AEDS or other treatments might be most effective for different children is one of the highest priorities for research into how SCN8A works – and how to improve the condition of our children. 

 

What are some of the related medical challenges these children experience?  Many of our children experience other complex and even life threatening medical conditions. Again, our survey of 20 children in our family group revealed the following:

 

  • G-tube (feeding tube) dependent              50.0%

  • Pulmonary/unsafe swallow                       40.0%

  • Scoliosis                                                     30.0%

  • Visual (cortical blindness)                        25.0%

 

  • Other common medical Issues

    • Reflux

    • Chronic constipation

    • Laryngomalacia

    • Sleep irregularity

    • Myelin disorder

    • Dystonia

    • Liver function (side effect of Valproate)

    • Hyperplasia of gums (side effect of Phenytoin)

 

How do I find a qualified doctor – or assess whether current doctors are the right fit for my child? This is a tough area since we all feel so reliant on doctors to make some sense of this mysterious disorder – and know what’s best for treating our children.

 

Dr. Michael Hammer, the first to identify the SCN8A gene in his own beautiful daughter, is building a wonderful interactive website (discussed further below) which will soon be providing more structured and specific guidance on this issue – including recognized neurologists with established expertise who agree to be accessible for consultations with doctors treating SCN8A for the first time.

 

But in the meantime, here are some of our thoughts:

 

First – trust yourself and your own instincts – absolutely no one knows your child better than you do – and it is critical to be observant and proactive in tracking and reporting changes in your child’s condition to your child’s neurologist – and possible effects of different medications. Speak up – trust yourself.

 

That being said, you definitely need an experienced – and conscientious – neurologist, if not further sub specialist,  including an epileptologist and a genetic neurologist. Given the extremely small number of identified cases, depending on where you live, you probably can’t hold out for a doctor who has already been treating other SCN8A cases – there are just so very few and certainly not close to all the families constantly being diagnosed. But you should be confident that your doctor is taking the initiative to remain current with the continually emerging literature on SCN8A. Even though clear dispositive answers have not yet emerged, this developing information is critical for your doctor to follow if he is to make the most informed treatment decisions for your child. Again – ask questions and trust yourself.

 

Also we have found coordination of care by the many specialists Elliott sees is extremely important (e.g. GI and pulmonary). We struggled with this for some time – and finally came upon a godsend when we found a dedicated hospitalist who runs a Complex Care program at Children’s Hospital here in D.C. Sometimes hospitalists focus only on in-patient cases, but we have been lucky to find someone who also is a ready resource and coordinates care for all our out-patient appointments as well. It is certainly worth asking to see if there is a program like that at your hospital.

 

Finally, not everyone would qualify or be willing to go this route, but we have found the hospice program to be a valuable resource in helping stay on top of Elliott’s condition on an ongoing basis with experienced RN visits to the house – and available on call 24 hours a day. Elliott has rather severe respiratory complications due to his extremely low tone – and the array of equipment we have at home combined with the knowledgeable eye of his hospice nurse, had helped keep Elliott out of the hospital for nearly 9 months – after 6 consecutive visits over a two month period last summer. Families should understand that hospice for children is far more flexible than with adults – while a life threatening condition must be present, enrollment requires no abandonment of treatment – so our view was we gave up nothing and gained excellent support by enrolling Elliott in a hospice program. And happily Elliott has been in the program over eight months now. Children have been in the program for years – and some even “graduate" when their condition is so improved to reduce an earlier high risk that qualified them for the program.

 

What are my risks of having another child with the same mutation? This is of course the domain of your neuro-geneticist and genetic counsellor. But because this is such a common question and limited discussion of the process of understanding the risks exists, here is how Gabi and John, Elliott’s parents, approached the issue:

 

The best information we could get indicated that Elliott’s genetic mutation was "de novo,” meaning it was not inherited from either John or myself but occurred spontaneously in Elliott. John and I have both undergone genetic testing for Elliott’s SCN8A mutation, and they did not find it in us. However, there have been other parents who did not think that they had it, and yet they had more than one child with an SCN8A mutation. The most likely explanation is something called genetic mosaicism, in which the genes in one part of your body can differ from the genes in other parts of your body. In this scenario, the cells in most of our body (including our blood) might have the normal, healthy version of the SCN8A gene, but one of us might have the mutated version in our reproductive organs (called gonadal or germline mosaicism). If that were the case then we could pass the mutated version on to multiple children, even though a blood test would say that’s not possible.

 

Gonadal mosaicism is rare, but not rare enough to calm our nerves. We had hoped to rule it out before we started trying to have a second child, but unfortunately, gonadal mosaicism is very difficult to test for. We did what testing we could, but we were not able to eliminate the possibility completely.

 

In reality, the only way we could tell whether our next child would have this mutation was to get pregnant, wait until almost halfway through the pregnancy, and then test the fetus itself by doing an amniocentesis. And that is what we did, which made the first 4.5 months of the pregnancy incredibly difficult. The “what if” was constantly in the backs of our minds, even after I started to feel the baby kicking. At week 18, we had the amniocentesis. Several tubes worth of amniotic fluid were drawn from the amniotic sac and sent out for genetic testing. We were told that the wait could be up to three weeks, but luckily the results back came after only a week and a half: Baby #2 does not have the same SCN8A mutation as Elliott.

 

That testing did provide some relief, but we still have concerns. For one thing, while we are fairly confident that Elliott’s SCN8A mutation is the source of his troubles, we can’t be certain. Because so little is known about the mutation, it could very well be that his SCN8A mutation is harmless and the real culprit is still unknown to us.  Or, it could be that his SCN8A mutation really is damaging, but that he also has a second harmful mutation that we don’t know about that is causing some of his more extreme health issues. Both of these scenarios are unlikely, but possible. And even if Baby #2 is free from whatever it is that Elliott has, that just puts us in the same boat as all other expecting parents.  The testing we’ve already had done can rule out a few issues such as Down Syndrome, but otherwise, this baby is at the same risk as any other for anything that can afflict a kid – genetic or otherwise – from autism to leukemia. All of those things are farfetched, but we’ve been hit by lightning before and we still worry that we might somehow have a second sick child. Once bitten, twice shy.

 

Recently a family working with a geneticist at London’s Great Ormonds Street Hospital (GOSH) reported on a newer and earlier emerging approach. They have started using a new screening technique that is less invasive and can be done as early as 9 weeks. Blood from the baby passes through the placenta into the mother’s blood and a small trace of this blood can be used to locate any mutations on the SCN8A gene. So they simply take a blood test from the mother before pregnancy and then again after 9 weeks. GOSH is now preparing for the first use of this test for SCN8A. This option is clearly just emerging, but worth discussing with your geneticist.

 

Additionally, we recently learned about an additional option other than prenatal diagnosis.  It is possible to do IVF and preimplantation genetic diagnosis (PGD), which can be costly and may not be covered by insurance.

 

How/Where to Get Help AND Help Accelerate Progress

 

Join Online Private SCN8A Family Forum: There is a rapidly growing private online support group of SCN8A families/caregivers. Everything is shared there and as a parent or primary caregiver of a child with an SCN8A mutation, you would be most welcome to join.

Just write Juliann Bradish at scn8afamilies@gmail.com and share some information about yourself and your child.

 If you like the FAQ but have many more questions – and want to participate in a dialogue with other parents and caregivers of children struggling with the effects of an SCN8A mutation, this Family Forum is definitely the place you want to be.

 

TAKE ACTION to HELP you Can Make a Difference

  • Participate in Hammer Registry: Dr. Michael Hammer, a genetic researcher who identified the first human case of SCN8A in his own daughter, has devoted himself to further research and networking of SCN8A families. He is in the beta stage of developing a powerful and exciting new tool which will be an open resource for not only families but also clinicians and researchers. A central component of the resource will be case histories of as many SCN8A cases as possible which will be collected and published on a de-identified basis for an interactive website.

 

The single most important thing you can do as an SCN8A family to help advance understanding of SCN8A is to participate in this database, sharing information on the condition, treatments and outcomes of your children.  Please consider participating; contact him directly at mfh@email.arizona.edu or hammeruofa@gmail.com. The skeleton of the site, including its objectives, are available at www.scn8a.net

 

  • Participate in the Rare Epilepsy Network:

To expedite research into the rare epilepsies, ten rare epilepsy foundations joined forces with the Epilepsy Foundation, Research Triangle Institute, Columbia University and New York University to create the first ever Rare Epilepsy Network (REN).  The REN is building a comprehensive patient registry to collect information about rare epilepsy patients to better understand these conditions, improve treatments, and improve the lives and quality of care for patients living with them. A registry gathers and keeps information about people with a certain condition to support and encourage research. The information people provide is stored in a secure database; Information is given to researchers without names or identifying information of participants.

 

 

Wishes for Elliott has recently joined the Rare Epilepsy Network and SCN8A will now officially be among the rare epilepsies for which they will gathering data. Efforts are underway to streamline the data entry for the REN, which will include all epilepsies, with the data for the dedicated SCN8A database Dr. Hammer is creating. To enroll, please visit the Rare Epilepsy Network at https://ren.rti.org/.

 

  • Advance genetics epilepsy research by registering your completed Whole Exome Genetic test results – The Epilepsy Genetics Initiative (EGI) is a partnership of Citizens United for Research in Epilepsy (CURE), the National Institute of Neurological Disorders and Stroke (NINDS) and other strategic partners. EGI  is dedicated to connecting patients, clinicians, and researchers through a database of the genetic data of people with epilepsy.

 

The data (exome data) will be screened for known genetic causes of epilepsy and will be re-analyzed, at least every 6 months, to look for new genetic causes of epilepsy. Information will be reported back to the treating doctor and if the person with epilepsy agrees, the data will also be used for research to help scientists better understand epilepsy. 

 

Anyone who has been diagnosed with epilepsy and has had a test called exome sequencing done can be a part of EGI. People with epilepsy may enroll at any one of the 8 EGI enrollment sites around the globe or be enrolled remotely with the help of their doctor and with support from the EGI Team. Contact EGI for more information at EGI@CUREepilepsy.org. - See more at: http://www.cureepilepsy.org/EGI/patients.asp#sthash.DXndzMtJ.dpuf

 

Wishes for Elliott is honored to be included as a resource for families newly diagnosed with SCN8A and is working on additional ways to partner with CURE in the future.

  • Participate in Emerging studies – Researchers are continually developing new approaches and studies to expand the understanding of SCN8A mutations. Your first contribution is to register in the Hammer and eventually the REN data base – that’s where researchers can quickly get an overview of the characteristics of the range of SCN8A cases worldwide – important in devising their research plans, hypotheses, and variables. There are rigorous protocols governing the outreach by scientists to invite participation in studies – but we will try and serve as an intermediary to help families be aware of potentially emerging studies. Information will also routinely be shared on the Private Family Forum and Dr. Hammer’s interactive website as noted above.

 

  • Share your personal journey – Consider starting a Facebook page or a blog; or contribute to the Wishes for Elliott site. We as parents need to aggressively increase the public profile of the diverse faces of SCN8A. Check our Wishes for Elliott Facebook page at www.Facebook.com/WishesforElliott. It’s a wonderful tool for sharing the ups and down and building your own community of supporters.

 

  • Raise Funds to Support Research – help raise funds to support SCN8A research. You can start by advocating in your own community and support ongoing or new SCN8A research efforts. Consider providing support to Wishes for Elliott where we remain committed to supporting cutting-edge research and collaboration efforts that would not otherwise move forward.

 

  • Become a Participating Family in Wishes for Elliott – Wishes for Elliott devotes ALL its resources to advancing the state of knowledge of SCN8A and sharing that information with families and the community at large.

 

One simple way to become a part of our growing community is to simply share a picture of your child which we can include among the “Faces of SCN8A". In addition, we are happy to provide a link directly to your own facebook page, website, or fundraising efforts. Simply write us at wishesforelliott@gmail.com. Another way is to submit a story which we can include on our Caretaker's Corner.

 

Consider becoming a donor to Wishes for Elliott  we depend on donations to continue our work. We have expended everything we have collected to date to convene the first SCN8A scientific conference and help coordinate the negotiation and publication of a Consensus Statement of the participants. But the work is just beginning.

 

In our current campaign, we are focusing on raising funds to immediately move forward with some of the most promising research priorities identified by the participants in the first scientific conference on SCN8A just held in April, 2015. A primary outcome of the conference will be publication on a Consensus Statement identifiying the most promising projects requiring some seed funding.

If you are in a position to support these efforts, it is clear that every bit of help will make a difference. Click one of the buttons at the bottom of the page to either donate directly to Wishes for Elliott or our work at Children’s Hospital. While we are amazed by our success to date, we have only a relatively small group of donors – and will be very limited in supporting much broader efforts until we can develop a much broader base of support.

 

Resources

 

PRESENTATIONS by participants in Wishes for Elliott sponsored First SCN8A Conference of Experts, April, 2015 are available on the SCN8A Conference page.

 

JOURNAL ARTICLES ON SCN8A – (links provided when available)

  1. Blanchard MG, Willemsen MH, Walker JB, et al. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy. J Med Genet 2015. (http://dx.doi.org/10.1136/ jmedgenet-2014-102813). B

  2. de Kovel CG, Meisler MH, Brilstra EH, et al. Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy. Epilepsy research 2014;108:1511-1518.

  3. Dyment DA, Tétreault M, Beaulieu CL, et al. Whole-exome sequencing broadens the phenotypic spectrum of rare pediatric epilepsy: a retrospective study. Clinical Genetics 2014:n/a-n/a.

  4. Estacion M, O'Brien JE, Conravey A, et al. A novel de novo mutation of SCN8A (Nav1.6) with enhanced channel activation in a child with epileptic encephalopathy. Neurobiology of disease 2014;69:117-123.

  5. Larsen J, Carvill GL, Gardella E, et al. The phenotypic spectrum of SCN8A encephalopathy. Neurology 2015;84:480-489.

  6. Mercimek-Mahmutoglu S, Patel J, Cordeiro D, et al. Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epilepsia 2015:n/a-n/a.

  7. O'Brien JE, Meisler MH. Sodium channel SCN8A (Nav1.6): properties and de novo mutations in epileptic encephalopathy and intellectual disability. Frontiers in Genetics 2013;4.

  8. Ohba C, Kato M, Takahashi S, et al. Early onset epileptic encephalopathy caused by de novo SCN8A mutations. Epilepsia 2014;55:994-1000.

  9. Oliva M, Berkovic SF, Petrou S. Sodium channels and the neurobiology of epilepsy. Epilepsia 2012;53:1849-1859.

  10. Olson HE, Tambunan D, LaCoursiere C, et al. Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome. American journal of medical genetics Part A 2015.

  11. Singh R, Jayapal S, Goyal S, Jungbluth H, Lascelles K. Early-onset movement disorder and epileptic encephalopathy due to de novo dominant SCN8A mutation. Seizure - European Journal of Epilepsy;26:69-71.

  12. Vaher U, Nõukas M, Nikopensius T, et al. De Novo SCN8A Mutation Identified by Whole-Exome Sequencing in a Boy With Neonatal Epileptic Encephalopathy, Multiple Congenital Anomalies, and Movement Disorders. Journal of child neurology 2014;29:NP202-NP206.

  13. Veeramah KR, O'Brien JE, Meisler MH, et al. De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP. American journal of human genetics 2012;90:502-510.

  14. Wagnon JL, Korn MJ, Parent R, et al. Convulsive seizures and SUDEP in a mouse model of SCN8A epileptic encephalopathy. Human molecular genetics 2015;24:506-515.

  15. Kong W, Zhang Y, Gao Y, et al. SCN8A mutations in Chinese children with early onset epilepsy and intellectual disability. Epilepsia 2015;56:431-438.

 

GOVERNMENT ORGANIZATIONS

 

U.S. National Library of Medicine 

 

NIH’s National Institute of Neurological Disorders and Stroke 

 

Infantile spasms

Seizures

Hypotonia

 

Epilepsy Phenome/Genome Project

EPGP is an NINDS study looking for siblings who both have epilepsy, and people who have other specific types of epilepsy.

 

NIH Undiagnosed Diseases Program (UDP)

 

The Office of Rare Diseases Research aims to improve the lives of people with rare diseases by coordinating collaborative research efforts.

 

The Genetic and Rare Diseases Information Center (GARD)

GARD was created in 2002 by the National Human Genome Research Institute (NHGRI) and the Office of Rare Diseases Research (ORDR), two agencies at the National Institutes of Health (NIH). GARD provides the public with access to current information about genetic and rare diseases.

 

PRIVATE ADVOCACY and SUPPORT ORGANIZATIONS

 

Epilepsy Foundation; Email: postmaster@efa.org 

 

Citizens United for Research in Epilepsy; Email: info@cureepilepsy.org

 

American Epilepsy Society;  AES Research

 

International League Against Epilepsy 

 

National Organization for Rare Disorders (NORD); Email: orphan@rarediseases.org

 

Global Genes Project 

 

Intractable Childhood Epilepsy Alliance; Email: info@ice-epilepsy.org

 

The Charlie Foundation; (800) FOR-KETO (367-5386)

 

Complex Child E-Newsletter

 

Courageous Parent Network 

 

Exceptional Parent Magazine

 

In Need of Diagnosis (INOD) 

 

National Society of Genetic Counselors - There are a few genetic counselors in the US who specialize in epilepsy genetics (Bosteon Children's, Children’s of Philly and Columbia currently have specialists). Although, not all GCs will be knowledgeable specifically about SCN8A, it may still be helpful for context and discussion about risks with additioal children.  

 

Syndromes without a Name - USA (SWAN-USA) 

 

SUDEP Aware; Email: info@sudepaware.org

 

The Mighty blog 

 

 

 

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Last feeding therapy before food by mouth stopped due to aspiration risk