Hillary Savoie: Parents as citizen scientists

The author with 3-year-old Esmé at their home in New York. (Tracey Buyce Photography)

In my last post I explained the genetic testing process that led to my daughter Esmé receiving results of two mutations of unknown significance. One, on the gene PCDH19, was discovered in 2012 with the GeneDx infantile epilepsy panel. The other, on SCN8A, was found with whole exome sequencing, also through GeneDx, in 2014.

When we received the SCN8A result, I was fascinated by the notion that it would have been included in our original epilepsy panel had we only waited a handful of months. In fact, in the time since Esmé’s original test in 2012, almost 20 new genes have been added to the GeneDx Infantile Epilepsy panel.

This realization blew open the model I’d had in my head of the stability of genetic diagnosis—a list of disorders to check off—and replaced it with an image of a quickly expanding set of genetic knowns paired with more rapidly expanding unknowns: undiscovered mutations, multiple gene interaction, epigenetics and so on.

Being a rare parent

Standing in the middle of this new medical reality are patients and parents like myself who struggle to find answers. And when we do find answers, such as they are, we struggle to know what to do with them. The rapidly expanding list of rare genetic epilepsies means that clinicians may have little or no knowledge of our child’s disorder. It means that little or no research may have been published or conducted on the disorder that matters most to our lives.

Esmé Savoie in the Neonatal ICU, where her family was informed that she likely had a genetic disorder.
Esmé Savoie in the Neonatal ICU, where her family was informed that she likely had a genetic disorder.

And this means that we must add to the long list of skills we develop over years of medical emergencies, IEP meetings, hospital admissions and hours of various therapies: medical researcher, rare disorder educator, epilepsy research sleuth and social media medical networking maven.

To arm ourselves with the knowledge to protect our children, we are turning to Facebook groups populated by other parents and caregivers. We share information about treatments, symptoms and prognoses with the kind of nuance that would impress most medical practitioners and could inspire dozens of scientific research projects. And, increasingly, many of us are going steps further, seeking out researchers around the world, asking science to move faster for our children.

The SCN8A Epilepsy Community

The discovery of the SCN8A gene in humans was made by a parent of a child with SCN8A Epilepsy, Dr. Michael Hammer, a geneticist at the University of Arizona. Sadly, it came just weeks after the death of his daughter, Shay, due to Sudden Unexplained Death in Epilepsy (SUDEP). (For more on Dr. Hammer’s discovery watch The Gene Detective’s Journey.) In honor of Shay, Dr. Hammer worked with a team to publish their findings and help others with SCN8A mutations find answers.

SCNA-group shot
Hillary and Esmé Savoie, Dr. Michael Hammer, Juliann and Adeline Bradish, Gabi and Elliott Conecker met at the first SCN8A research conference, organized by Wishes for Elliott. (Anne Scherrer)

It wasn’t long before Juliann Bradish, whose 9-month-old daughter, Adeline, had recently been diagnosed with SCN8A Epilepsy, reached out to Dr. Hammer. Juliann was a pharmacist by training, and she quickly got to work creating an SCN8A family Facebook group, adding families as they were referred to her and gathering information about genetic mutations, symptoms and responses to drug treatments. With this information, Juliann is helping families submit skin biopsies to the University of Michigan, where Dr. Jack Parent is doing SCN8A research with induced pluripotent stem cells made from cells donated by SCN8A patients—and helping researchers find patients with a particular mutation of interest. Juliann has recently joined us at The Cute Syndrome Foundation as the SCN8A Advisor, helping drive our SCN8A Epilepsy research and education agenda.

In April of this year, the Conecker family, of the Wishes for Elliott Foundation, organized a conference for researchers to share their work on SCN8A Epilepsy. This conference yielded invaluable information and research connections that will no doubt accelerate the pace of SCN8A research.

Crowdsourced data

It isn’t only parents with scientific backgrounds and foundations that are advancing the understanding and treatment of rare disorders. Since there are currently around 100 documented cases of SCN8A Epilepsy worldwide, it is safe to say that most are being treated by clinicians who have limited or no experience with SCN8A or access to SCN8A data. Therefore, the parents who follow the successes and failures of various treatments and observe the phenotypes of other children are often the experts in the room.

Yet their ability to share their collective knowledge with medical practitioners can be limited, because there exists no clearly established avenues to do so. In the SCN8A community, for example, we often see one frustratingly consistent problem.

Many children with SCN8A Epilepsy are prescribed Keppra, a common first-line-of defense anticonvulsant. This drug works well for SCN1A epilepsy, sometimes diagnosed as Dravet Syndrome, a more commonly known genetic epilepsy that can have a similar presentation to SCN8A epilepsy. Both SCN1A and SCN8A encode voltage-gated sodium channels (which help neurons build up the membrane potential that enables them to fire), so clinicians may assume that they should be treated similarly. However, SCN1A epilepsy is caused by a loss of function in channels on inhibitory neurons, whereas SCN8A epilepsy is usually caused by a gain of function in channels on excitatory neurons.

Within the SCN8A community, we time and time again see children with SCN8A experience dramatically worsening symptoms on Keppra. Time and time again, we tell new parents to explain to their doctors that Keppra should not be prescribed for children with SCN8A. And, all too often, parents are afraid to speak up or their information is not heeded.

And, all too often, the children bear the brunt of that lack of communication.

A new practice paradigm?

Understandably, practitioners are in a bind when it comes to information provided by their patients’ caregivers. They have few ways of validating it. Clinicians are rarely active within parent communities, due to restrictions of the groups themselves or their institutions, or their own time constraints. And certainly, there is the potential within parent groups to jump to conclusions based on limited group information.

At the same time, parents are often unbelievably knowledgeable about their children, and the value of their observations cannot be underestimated. There are emerging mechanisms to take advantage this knowledge—including databases built or populated by parent information. However, these mechanisms do not yet go far enough to bring basic disorder information to the people who most need it. Science and medical practices must continue to evolve to meet the changing relationships among clinicians, researchers, institutions and the citizen scientists who hold so many answers that are needed to better understand and treat rare disorders.