Rare Disease Legislative Advocates

Last week I spent two days around the halls of Congress, lobbying as part of the Rare Disease Week activities on Capitol Hill, organized by the Rare Disease Legislative Advocates (RDLA). Each year, hundreds of rare disease advocates from all across the country and all political stripes descend on Washington DC to help lawmakers better understand what it means to live with a rare disease, and to advocate for the funding and support to more quickly diagnose and better serve individuals with rare diseases. It was great to represent the KCNQ2 Cure Alliance and all of our families, and to speak to so many politicians. It was also amazing to be part of such a large, powerful and positive group. The Rare Disease Week lobbying effort was divided into two halves, Monday was for training and prep, and Tuesday was the day to knock on doors and get face-to-face with our representatives. If I tried to write about everything that I saw and everyone that I talked to over the course of the two days, this blog would be way too long. But I want to highlight a few keys things that I saw during my two days that I think are important to share.

Before walking into the halls of Congress, RDLA brought us all together to talk about what we should expect and the current state of affairs of rare diseases in Congress. The topic of most interest to me, and likely many KCNQ2 families, was newborn screening for rare diseases. I wasn’t sure what to expect but immediately it was clear that there were reasons to be hopeful for progress. In a very partisan city, I heard rare disease issues referred to as either “bi-partisan” or “non-partisan” by members of both parties and by lobbyists. An early and correct diagnosis of a rare disease means more appropriate treatments can be administered faster, and this has powerful benefits, including lowering the cost of care for a person’s lifetime. No one is against that. Current legislation that ensures newborns are screened for a set of rare diseases expires this year, so one of our asks of our representatives was for reauthorization of the act that mandates rare disease screening when a child is born.

Sitting in a room of nearly five hundred people, I was struck by just how much larger this is than I thought. Being the parent of a child with a very rare disease can be isolating. You are often dealing with a unique set of circumstances and the “typical” world can feel miles away. But getting into a room with nearly 500 people from all over the country changes that. It becomes easier to see that gathering together all rare diseases means that we now have something much more common. In fact, if you brought together all Americans who live with rare diseases, you would have the second largest state in the country — of approximately 30 million people! Our needs are often overlapping and the impacts on family members and caregivers means that the circle gets bigger and bigger. The number of people impacted by rare diseases is, in fact, very large. We are not a small voice at all.

Another connection to a bigger picture also became clear: research on rare diseases can help people with more common ones. A second legislative ask was increasing funding to the National Institutes of Health (NIH) and the FDA. This is important because the FDA and the NIH provide grants that take the risk out of studying rare diseases, risks that would likely not be profitable for a company to take on. But in doing research on rare diseases, doctors have come across medicines that help much more common ones. Research on three different rare diseases has led to medical breakthroughs in arthritis, osteoporosis, and Ebola. In our own world, KCNQ2 has a connection to tinnitus, which affects more than 50 million Americans including many veterans. Our worlds are much larger and more connected than we think.

On the second day, rare disease advocates descended upon the halls of Congress, taking part in hundreds of meetings to make the case for rare disease funding and research. I visited the offices of three Maryland legislators: Representative Jamie Raskin, Representative Steny Hoyer, and Senator Ben Cardin. All three are strong allies on important rare disease issues, including newborn screening and increased funding for the NIH and the FDA. But even when you know you are walking into a friendly office, the experience of advocating for your child to congressional officials is a weighty but powerful responsibility. And although it’s impossible to sum up the experience of having a child with KCNQ2 in a 60-second elevator pitch, I emphasized the importance of research and access to early screening and also shared a glimpse into the world of caring for a child with a rare disease.

And I was not alone. The Maryland contingent was the largest of any state and we had at least 7 people in each meeting. I talked about the benefits of an early diagnosis for our daughter Lucy and how easy and beneficial that was to replicate with more newborn screening. Others talked about NIH and FDA funding. There was a wide variety of people in the room. Other parents and people living with a rare disease, a fellow from NIH working on rare diseases, genetic counselors from Children’s National Medical Center and representatives of different rare disease foundations.

As we spoke it became clear just how powerful our stories are. Staff members were open and eager to hear what we had to say. Serving constituents is a priority for many members of Congress. When you want to speak to your representative, odds are high they will listen. When you have a compelling story and a clear message, odds are high that they will help. All day long as we walked through the various buildings housing congressional offices we kept running into groups from other states. This included not only rare disease advocates, but also neurologists from all over the country, activists fighting global poverty, and members of the Veterans of Foreign Wars. These doors are open and the people inside are interested.

It was a day where we could see the strength of big numbers, but we need more. We want to increase the KCNQ2 voice during Rare Disease Week, so consider if this is something you could participate in and make it next year. But more importantly, advocacy doesn’t just take place in Washington DC. Congress represents us all — KCNQ2 families, researchers, and clinicians. And while each year RDLA ensures that our voices are heard during Rare Disease Week in Washington DC, they also organize lobby days in August in each legislator’s home district. That means your representatives can meet with you close to home. Let’s make sure they all have a chance to learn about our amazing KCNQ2 kids. Please reach out to us if you are interested in making your voice heard and helping support our whole KCNQ2 community. We can help you make it happen. I had the good fortune to speak with three lawmakers who were all receptive to our message. But any chance to make your voice heard on KCNQ2 is powerful and valuable.

In the weeks to come, I will be following up on our legislative asks and will send updates on the feedback I get. And as we get closer to August we will be reaching out for people to join us for state-level lobbying efforts. We look forward to hearing from you about how you can help.

KCNQ2 Cure Alliance Announces Collaboration with KCNQ2.e.v.

KCNQ2 Cure Alliance Announces Collaboration with KCNQ2.e.v., of Trier, Germany

KCNQ2 Cure Alliance today announced it is collaborating with KCNQ2 e.v., of Trier, Germany. Simone and Sebastian Bethge, whose son, Sepp, is affected by a KCNQ2 mutation, founded KCNQ e.v. to raise funds to support research to find a cure for KCNQ2 developmental and epileptic encephalopathy.

The collaboration between the two organizations strengthens the connections between European families affected by KCNQ2, and the rest of the international patient community. The relationship furthers our ongoing mission to support KCNQ2 families and find a cure for people living with KCNQ2 developmental and epileptic encephalopathy.

“Leveraging alliances with other organizations throughout the world provides us a truly global reach and scale to access all available funding sources, bring in international expertise, and help support families within their regional community” said Jim Johnson, President of KCNQ2 Cure Alliance, “This allows us to build upon and replicate the success we have experienced with awareness, fundraising, research and community engagement with our Australian presence led by Board Member, Sara James”.

“We are excited about this mutually beneficial collaboration with the KCNQ2 Cure Alliance and look forward to all that we will accomplish together,” added Sebastian Bethge of KCNQ2 e.v.”

___________________

KCNQ2 Cure Alliance erklärt die offizielle Zusammenarbeit mit KCNQ2.e.v. Aus Trier, Deutschland.

KCNQ2 Cure Alliance gab heute die Zusammenarbeit mit KCNQ2 e.v. aus Trier, Deutschland, bekannt. Simone und Sebastian Bethge, deren Sohn Sepp von einer KCNQ2-Mutation betroffen ist, gründeten KCNQ e.v. um Gelder zur Unterstützung der Forschung zu sammeln und um ein Heilmittel für die Genmutation KCNQ2 zu finden.

Die Zusammenarbeit zwischen den beiden Organisationen stärkt die Verbindungen zwischen den von KCNQ2 betroffenen europäischen Familien und dem Rest der internationalen Patientengemeinschaft. Die Beziehung fördert unser gemeinsames Ziel KCNQ2-Familien zu unterstützen und ein Heilmittel für Menschen zu finden, die an der Krankheit KCNQ2 leiden.

“Die Gründung von internationalen Bündnissen mit gleichgesinnten Organisationen weltweit, bietet uns eine wirklich globale Reichweite und Grösse, um auf alle verfügbaren Finanzierungsquellen zuzugreifen, internationale Expertise einzubringen und Familien innerhalb ihrer regionalen Gemeinschaft zu unterstützen”, sagte Jim Johnson, Präsident der KCNQ2 Cure Alliance, “Die Zusammenarbeit mit KCNQ2 e.v. erlaubt es uns die erfolgreiche Arbeit von Aufklärung, Forschung und Engagement mit unseren australischen Partnern (unter der Leitung von unserem Vorstandsmitglied Sara James) auszubauen und zu erweitern. ”

“Wir freuen uns auf die Zusammenarbeit mit der KCNQ2 Cure Alliance, zwei Organisationen mit dem gemeinsamen Ziel diese seltene Krankheit zu erforschen“, fügte Sebastian Bethge von KCNQ2 e.v hinzu.

AES 2018

AMERICAN EPILEPSY SOCIETY 2018 and KCNQ2

The annual meeting of the American Epilepsy Society (AES) is the premier scientific meeting for the physicians, scientists, pharmaceutical industry, and patient groups engaged in epilepsy and related diseases, such as KCNQ2. Our time at the AES meeting in New Orleans this month was a time of learning, seeing old friends, building new relationships, and advancing our collaborations. Here’s a run-down of some of the things the KCNQ2 Cure team was involved in during the conference.

RARE EPILEPSY NETWORK

During the conference, we always appreciate the roundtable organized by the Rare Epilepsy Network (REN), for which one of our board members is a member of the Steering Committee. REN brings together patient advocates representing various rare epilepsies, such as Lennox Gastaut Syndrome (LGS), Dravet, CDKL5, SCN2a etc, along with physicians who treat those patients. The discussion each year has a theme, and this year focused on the need for Centers of Excellence for the treatment of rare epilepsies like KCNQ2. These centers could bring together the neurologists with expertise in the primary condition affecting our children, along with other experts that patients need to see, in order to get a comprehensive evaluation of the patient at one location and at a single visit. The specialists that would be needed at these centers of excellence could include the neurologist, gastroenterologist, vision specialist, hearing specialist, feeding specialist, etc., along with a coordinator to organize the appointments, all under one roof. Not only would this add convenience for the patients, but it would also bring together a group of physicians who gain deeper experience in their needs and greater insights into their treatment. This network of Centers of Excellence could also serve as the framework for collecting data for a natural history study and conducting clinical trials when for treatments under development. This type of initiative could have significant benefits for our KCNQ2 community, but can only be accomplished through collaborations like REN and our related rare epilepsy community.

DRAVET SYNDROME and KCNQ2

Another good opportunity for collaboration every year is at the Dravet Syndrome Foundation (DSF) roundtable. We are able to learn so much from the work of the DSF, which is focused on one of our “sister” mutations, mutations of the sodium channel that are related to our potassium channel mutation. While there is the biological connection, we also benefit from the DSF’s longer history (this mutation was known for years before KCNQ2 was identified) and larger more established patient population. Not only do many of the same experts treat Dravet and KCNQ2 patients, but many of the scientific discoveries and potential treatments for Dravet have the potential for benefit in the treatment of KCNQ2. One such possibility is a drug which showed good benefit for the treatment of Dravet, Zogenix’s, Fintepla (also known as ZX008, a formulation of fenfluramine), which could be approved for the treatment of Dravet Syndrome and Lennox-Gastaut Syndrome next year. Fintepla works by modulating both the serotonin receptor and the sigma-1 receptor. Because this mechanism is not specific to the sodium channel in its treatment of Dravet, also was effective in LGS, and because of the commonalities between these disorders and KCNQ2, experts we spoke with believe it has potential in the treatment of KCNQ2. In addition to these nearer-term, traditional drug approaches, the Dravet community is looking into gene editing approaches like gene therapy and antisense technology. The research being done, which was presented by Encoded Therapeutics (working on gene regulation and gene therapy approaches for Dravet) and Stoke Therapeutics (on their antisense oligonucleotide technology which they have evaluated in animal models of Dravet), could help provide a roadmap for our own efforts and collaborations in these cutting-edge technologies.

PHARMACEUTICALS and KCNQ2

Many of the biopharmaceutical companies working on treatments for rare epilepsies were also well represented at the AES meeting and we had the opportunity to meet with some of them. Xenon, which has been very involved with KCNQ2 specifically, and presented at the KCNQ2 Cure Summit in September, is continuing to focus on its development of potassium channel modulators. Xenon continues to anticipate having its own pediatric form of retigabine (Potiga), now known as XEN496, ready to start a Phase 3 trial in young patients with KCNQ2 in the middle of 2019. Xenon’s next-generation potassium channel modulator, XEN1101, has had good safety results in healthy individuals, and is advancing into a Phase 2 trial in adults with focal epilepsy early next year (and could also ultimately be effective for KCNQ2). Another company, Marinus Pharmaceuticals, is not currently involved in developing treatments for KCNQ2, but this could be another opportunity in which a treatment being studied in another rare epilepsy could also benefit KCNQ2 patients. Marinus is studying its drug, ganaxolone, in patients with CDKL5 mutations, and has also evaluated it in PCDH19 and other neurological conditions. Ganaxolone works by modulating the GABA receptor (a target known to have anti-anxiety, as well as anti-epileptic activity) and is not specific to a particular channel or mutation, so could also have benefit in KCNQ2.

There are other drug screening approaches that remain of interest for KCNQ2. Just before the AES meeting began, Pairnomix, the precision medicine company with which KCNQ2 Cure has previously collaborated, announced its merger with Q-State Biosciences. In talking to the team from Q-State and Pairnomix, it seems there may be additional opportunities to pursue with this drug screening approach, as Q-State brings to the table a range of new technologies. Q-State has developed human cell-based disease models and an imaging technology, which can more accurately and efficiently assess the activity of potential treatments in the cells grown in the laboratory. They also have the expertise to develop and test their own proprietary compounds in these cells, in addition to existing compounds that could be repurposed for KCNQ2.

RESEARCH and KCNQ2

Our medical and scientific experts have also been busy on our behalf, and we had the chance to host our own, informal, scientific roundtable with many of them. Dr. Ann Poduri of Harvard/Boston Children’s Hospital, who is spearheading our KCNQ2 Natural History Study, is continuing to enroll patients in the study. As part of this study, Dr. Poduri and her team are collecting medical information and samples from KCNQ2 patients that will improve the understanding of this relatively new disease. Many of our KCNQ2 families have already enrolled in this important study, but having broad participation across ages and mutations is key. We have other initiatives ongoing that are also collecting data on KCNQ2. Dr. Anne Berg, of Chicago Lurie Children’s Hospital, is conducting a survey of many of the rare epilepsies, including KCNQ2. At AES we continued our work with Dr. Berg to target this survey at the issues that are most important to our patients with KCNQ2. Many of our KCNQ2 families have already filled out all or part of the survey, but we are looking forward to getting enough families completing the surveys to get an analysis completed over the coming months. Dr. Ingrid Scheffer and her team in Melbourne are continuing their work on the important issue of sleep, which is a challenge for many KCNQ2 patients. Her sleep study is also ongoing and should generate some data that illuminates some of the issues faced.

While our community is growing dramatically, our discussions with experts have confirmed that the majority of cases of KCNQ2 are still not being diagnosed. As we learn more about KCNQ2, targeting treatments are under development, and more treatment options emerge, it is increasingly important to diagnose as many patients as early in their life as possible to get the best outcomes. KCNQ2 Cure Alliance has collaborated with Dr. Ed Cooper at Baylor University, and others, to establish the ERGENT (Early Recognition of Genetic Epilepsy in Neonates) program. ERGENT provides genetic testing, free of charge, for newborns suspected of having a KCNQ2 mutation. We are working on new approaches to spread the word about ERGENT so those affected can benefit from all of the developments in KCNQ2 treatment and care.

CENTER WITHOUT WALLS GRANT (CWoW)

It was exciting to learn the initial details of the CWoW grant award to a multi-center team led by Al George of Northwestern as the primary investigator.

The project will center on further identification of disease-causing mutations in epilepsy with KCNQ2 both being a focus as well as the first gene to be studied. As many of us know, the initial genetics reports provided to families detail a mutation with an unknown significance.

The work of the CWoW team will help to identify more precisely all of the mutations that are disease-causing and characterize the activity of passing potassium through the damaged channel in stem cell models. The hope is this can lead to testing compounds (possibly treatments) to be translational medicine to companies developing those drugs.

In January 2019, KCNQ2 Cure will be hosting a webinar with Al George who will go into more detail about the impact of the CWoW grant on KCNQ2.

While the AES meeting occurs but once a year, the new information and inspiration is setting us on course to pursue new collaborations, new potential treatment options, and we hope, the potential to improve the lives of the patients living with KCNQ2.

Ray Of Hope

When KCNQ2 Mom Holley Moseley decided to write the story of her daughter’s harrowing odyssey from desperately ill child to cheerful teenager, she knew exactly what the title had to be.

“She’s my Ray of Hope.”

Ray of Hope tells the story of RayAnn Heller, a little girl born with rare genetic epilepsy KCNQ2.

RayAnn
Ray Ann

RayAnn is also a born fighter, blessed with a mom who has backed her every step of the way. Ray of Hope is a story of drama and serendipity, of love and hope and what it means to be a family.

It’s also a story of how hard it is for families when a child suffers uncontrolled and lengthy seizures.

Holley says RayAnn took a powerful cocktail of anti-epileptic drugs but grew worse and worse. Holley says she was told to prepare for the unthinkable; they might need to say goodbye to RayAnn.

 

Instead, Holley wanted to say goodbye to medicines she believed weren’t working.

“I’m a nurse. I’m accustomed to taking doctors’ orders. But I’ve learned you have to trust your gut. You’re with your child all day every day. Doctors only see snapshots. Sometimes you need a second opinion. Or a third or a fourth.”

Holley realized there might be another path for her oldest daughter when she saw Weed, Dr. Sanjay Gupta’s documentary about medical cannabis.

Could this be the answer for RayAnn?

agovernor
Florida Governor Rick Scott

The first step was to gain legal access to the drug in their home state of Florida. Holley and RayAnn were among those who lobbied the legislature. In 2014, RayAnn was a poster child for the Compassionate Medical Cannabis Act. She had her picture taken with Florida Governor Rick Scott.

Holley says RayAnn received her first dose of what the family calls her “special medicine” on September 19, 2015, at 6:17 am. “I recorded it, the way I keep track of all her milestones.”

They took things slowly, under a doctor’s supervision. “Today, RayAnn is down from four anti-epileptic drugs to a small dose of one anti-epileptic drug and her “special medicine.”

Holley says RayAnn hasn’t had a seizure in more than a year and that her speech and understanding have increased. These days she uses her lobbying skills in a new way – to make sure she can volunteer with her youth group at the family’s church.

Each child’s journey is unique. There’s no guarantee that a medicine which works for one child will work for another. But Holley explains she wrote the story of her family’s search for answers so that RayAnn could be a Ray of Hope for others.

Holley Moseley spoke at the KCNQ2 Cure Summit on September 15, 2018.

To learn move about her book or purchase a copy click here

A Review of Variable Phenotypes and Neurodevelopmental Outcomes

Overview of Various KCNQ2 Epilepsy Mutation Types and Outcomes



KCNQ2 gene codes for parts of the potassium channel that limits repetitive signaling by the neurons. Mutations in this single gene can lead to very different paths of development and seizure activity. 



There are three different categories of outcomes for those affected: 1) Benign Familial Neonatal Convulsions (BFNC), 2) Benign Familial Infantile Convulsions (BFIC), or 3) neonatal epileptic encephalopathy.  For all of these KCNQ2 childhood epilepsies, seizures usually occur within the first week after birth. 



Patients with BFNS or BFIC have seizures early on, but they usually spontaneously disappear by one year and development for these children is good. 



Most patients with neonatal epileptic encephalopathy present with a specific pattern on their EEG (burst suppression or multiple focal spikes) and generalized tonic, or grand mal, seizures. There are three categories of epileptic activity for these patients: 1) the development of West Syndrome, with epileptic spasms in a small portion of patients, 2) relatively good control with anti-epileptic medications, 3) seizures spontaneously disappear after the patient turns one year old. The MRI in all of these categories is typically relatively normal. However, patients have lasting and significant developmental delays. 



Most of the cases of neonatal epileptic encephalopathy are de novo mutations, occurring spontaneously and not inherited from the parents. The KCNQ2 mutation occurs globally, regardless of ethnicity. 



Mutations in the KCNQ2 gene are the cause of about 8% of childhood epilepsies not caused by brain trauma. There are over 80 different genotypes or specific variations in the mutation in KCNQ2. The majority of these mutations (69%) are missense mutations, meaning part of the “code” in the gene is replaced with another random sequence. Other mutations are indel 16 (21%), meaning there is an insertion or deletion of nucleotides in the middle of a sequence, or splice-site mutations (10%), meaning there is a mutation at the end of a sequence.   



Depending on the specific variant, the mutation can affect a different part of the potassium channel. Which part of the potassium channel is affected appears to be related to the severity of the outcome (seizure severity and degree of disability) for the patient. However, there is not always a direct relationship between the specific variant of the KCNQ2 mutation and the outcome for the patient. For example, there have been cases of a family in which all inherited the same variant, but different members of the family had very different outcomes.  It is not understood exactly why this would happen, but there is a theory that it could be due to an interaction between KCNQ2 and other genes or due to environmental factors beyond the DNA. 



Treatment approach of patients suffering from KCNQ2 related epilepsy is not dependent of which variant or severity of outcome the patient has. Most cases can be controlled with phenobarbital, oxcarbazepine, vigabatrin, and valproate. Laboratory studies of retigabine (also known as Potiga or ezogabine) showed that it reversed the functional electrical current changes in cells. Additional studies of this and other treatments are recommended for this severe disease. 



Conclusion: The relationship between specific mutations in KCNQ2 and the severity of seizures and disability in patients is still not well understood by experts and additional studies are needed. 

Lee, I., Yang, J., and Li, S. (2018) KCNQ2-Associated Epilepsy: A Review of Variable Phenotypes and Neurodevelopmental Outcomes Neuropsychiatry, 8(1): 318-323. doi:10.4172 1000353

A possible link between KCNQ2- and STXBP1-related encephalopathies: STXBP1 reduces the inhibitory impact of syntaxin-1A on M current

Study finds a possible relationship between KCNQ2 and the STXBP1 gene that has been identified as a cause of Ohtahara Syndrome

Background: The potassium channels control the electrical currents sent by the neurons. Mutations of the KCNQ2 gene coding for a component of these potassium channels cause early-onset epileptic encephalopathies. Mutations in the STXBP1 gene, which codes for syntaxin binding protein 1, and causes Ohtahara Syndrome, can cause similar symptoms to those seen in patients with KCNQ2 mutations. The similarities in symptoms caused by these two different gene mutations suggest there is a possible link between STXBP1 and potassium channels.

Potassium channels are known to be modulated by syntaxin-1A, a protein encoded by the STX1A gene, which inhibits the electrical activity of the potassium channels (or M-current). This study evaluated whether the STXBP1 gene, which is a cause of Ohtahara Syndrome and is related to STX1A, prevents syntaxin-1A from limiting the activity of the potassium channel.

Methods: The study examined the electrical signals in cells grown with various mutation combinations to evaluate the interaction between the various proteins expressed by the STXBP1 and STX1A genes.

Results:
The study demonstrated that syntaxin-1A decreased the electrical currents (M currents) of the potassium channel by binding to the channel. The study showed that syntaxin binding protein 1 (encoded by STXBP1) did not directly affect the electrical current of the potassium channel, but it interfered with the binding of syntaxin-1A. In effect, syntaxin binding protein 1 stopped the syntaxin-1A from interfering with the potassium channel activity. When there is a mutation in the STXBP1 gene affecting the production of syntaxin binding protein 1 (as in Ohtahara Syndrome), the syntaxin-1A is able to interfere with potassium channel activity.

Significance:
The results show that there is a link between STXBP1 (a gene found to cause Ohtahara Syndrome) and potassium channels, indirectly, by way of the syntaxin-1A protein. It suggests that defects in the activity of the potassium channel similar to those seen with KCNQ2 mutations could also be caused by certain mutations in STXBP1. The protein syntaxin-1A may be important for regulating potassium channel activity and signaling by the neurons.

Devaux, J., Dhifallah, S., De Maria, M., Stuart-Lopez, G., Becq, H., Milh, M., Molinari, F. and Aniksztejn, L. (2017), A possible link between KCNQ2- and STXBP1-related encephalopathies: STXBP1 reduces the inhibitory impact of syntaxin-1A on M current. Epilepsia, 58: 2073–2084. doi:10.1111/epi.13927

KCNQ2: What’s in the Alphabet Soup?

kcnq2_defExperts have known for some time what the KCNQ2 gene does, and it was named accordingly – “K” for the scientific symbol for potassium, “CN” as an abbreviation for channel, and “Q2” for the subtype Q2. But even scientists only recently understood the wide range of different variations in the “source” of the mutations and in outcomes for affected patients.

KCNQ2 benign familial neonatal epilepsy

The KCNQ2 mutation can come from a variety of sources. It can be inherited from an affected parent that has the mutation, it can be inherited from a parent who carries the mutation in some of his/her cells (called mosaicism) but does not display the severity symptoms that would expect to be caused by that mutation, or can be a new or random mutation (de novo) occurring for the first time in the affected patient.

The KCNQ2 mutation was first recognized by experts as the source of Benign Familial Neonatal Epilepsy (BFNE) in 1998. In the years prior to that, scientists had followed generations of families who had experienced seizures as infants, but that generally resolved and developed normally. These individuals went on to have children of their own, some of whom inherited the mutation in the KCNQ2 gene coding for this mild variation of the disease. Until recently, when doctors saw seizures in the first days of life, or when testing showed a KCNQ2 mutation, they assumed it was likely a benign seizure disorder, BFNE.

KCNQ2 encephalopathy

However, as experts studied more patients, they saw some children who were more severely affected than their parents and began to wonder why. In these cases, the parents had developed normally because only some of their cells carried the mutation (they were mosaic), but passed on the severe mutation from the subset of their cells that were affected. So, in these cases, even though the parent seems to have the benign form of KCNQ2, it is possible for them to have a child with the more significant symptoms of KCNQ2 encephalopathy. In 2011, experts began to realize that KCNQ2 mutations can also cause the more significant developmental delays and more lasting seizures associated with KCNQ2 encephalopathy.

Original study discovering KCNQ2 encephalopathy :

KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy.

With this knowledge and with greater availability of genetic testing, doctors have been able to identify more severely affected patients with KCNQ2 mutations, even when there is no family history. In fact, in the majority of the cases of KCNQ2 encephalopathy – mutations causing the more severe form of the disease – the mutation is not inherited, but is de novo, or “new”. This makes sense when you consider that a severely affected person is unlikely to have offspring, so the specific variants that cause a severe outcome are not usually passed down through a family (unless only some cells are affected, as in the mosaic cases discussed above). Now that genetic testing is more available, doctors have also found that there are some de novo cases of benign epilepsy, in which a spontaneous KCNQ2 mutation causes a more benign outcome, which in turn may be passed on to subsequent generations as BFNE.

So what does this mean?

Historically, the severity of the outcomes was labeled according to the mode of inheritance, with “familial” or inherited being associated with benign variants and de novo being associated with more significant encephalopathies. Now that the genetic basis for the different outcomes is better understood, it is clear that the specific variant of the mutation is more important than whether or not it was inherited.

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Healthcare for Disabled Children Secured

irish bill

We are so excited to share the tremendous achievement of our own Mark Fitzpatrick of Dublin, Ireland.  Through Mark’s unwavering efforts over nearly three years, he has secured the right to much needed medical care for thousands of Irish children with disabilities.  Thanks to Mark, no new parents in Ireland will have to go through the stress of the medical card application process – and many potential rejections – when their world has just been turned upside down.

Father of KCNQ2 Child Moves Mountains to secure Healthcare for Children in Need

kcnq2 boy
Eric Fitzpatrick

 

As the parent of a child with KCNQ2 encephalopathy, Mark understands firsthand the importance of the availability of government support for the numerous pieces of specialized equipment necessary to care for his son, Eric.  In Eric’s case, he currently has seven pieces of equipment that came through Ireland’s medical card – his special bed, pram, bath seat, hoists, stander, and hi-low chair.  These expensive pieces of equipment and other medical necessities are out of the reach of most families without the government support provided by a medical card. 

 

Instead of just fighting the battle to get a medical card for Eric, Mark set off on a journey alongside two other advocates leading the effort to get needed medical care for the nearly 10,000 disabled children in Ireland whose parents struggle to care for them at home.  He did this so that the most vulnerable in Ireland have full and free access to healthcare in their own right and in their own name, no questions asked. Due to these changes in legislation, all disabled children forever more will have free access to all medication, equipment and therapies that are available in Ireland, and their parents will be spared the heartbreak that previously came with every medical card application or review.

irish government
Mark Fitzpatrick, Peter Fitzpatrick, and Kevin Shorthall of Our Children’s Health on day 597 waiting in front of the Irish government offices

Mark and his group “Our Children’s Health”, gained the support of many other organizations in this effort – The Special Needs Parents Association, The Jack and Jill Children’s Foundation, Down Syndrome Ireland, The Saoirse Foundation, The Irish Children’s Arthritis Network and The Genetic and Rare Diseases Organisation – all working together.   However, Mark spent much of his own time campaigning himself, standing outside of the government offices morning after morning, meeting with legislators and collecting signatures to bring about this important change. 

 

 

As the Minister for State Finian McGrath said in response to the passage of the bill; “I’m delighted that this is one less battle that parents and families of children with a disability will have to face. This previous medical card omission added to a constant struggle for families and caused further hardship and hurt.”

 Inspired by the fight Eric and his KCNQ2 friends fight every day, Mark moved mountains and we couldn’t be more proud!

 You can read the full bill here

You can read the press release from Minister Harris & Minister McGrath:

KCNQ2 and Rare Disease Day 2017

Denver, Colorado

kcnq2 awareness

The KCNQ2 Cure Alliance celebrated Rare Disease Day 2017 working to improve the lives of our children with efforts on multiple fronts. An international team of parents and KCNQ2 experts met in Denver today to set priorities for the coming year. At the same time, we were well represented in Washington D.C., as we joined hundreds of other advocates convening in the capital to raise awareness and advance issues facing patients with rare diseases.

At our meeting in Denver over the past two days, we laid out plans for many initiatives that we are excited to share with our community. We are getting ready to kick off our KCNQ2 Cure Awareness Week March 5-11th. Increasing awareness has helped accelerate the diagnosis of KCNQ2 encephalopathy and spurred rising interest by scientists and pharmaceutical companies in working on treatments. Details of the 4th annual KCNQ2 Cure Alliance Family and Professional Summit are really beginning to come together. The conference will be held in Boston, October 22-24, 2017. This year we are planning to expand on the 140 international teamparticipants who attended in 2016, with new speakers addressing some of the issues many of our children face daily and many opportunities for families to share their experiences and support each other. The location in Boston puts us close to the experts at Harvard Medical School’s Boston Children’s Hospital, which is spearheading our KCNQ2 natural history study. This is a unique opportunity for the team working on the study to interact with many KCNQ2 patients in a very short time, that we hope could accelerate the progress of the study. Over the course of our meeting we also brainstormed about how we might most effectively help our KCNQ2 community, and expect to roll out several new initiatives over the coming months as a result of these efforts. Reviewing the progress we have already made in such a short time, as well as the opportunity for further advances, left us feeling inspired to push forward with renewed excitement.

Washington, D.C.

We clearly can’t cure KCNQ2 alone, so Megan Roberts represented KCNQ2 Cure Alliance at Rare Disease day events in Washington, D.C. Rare Disease day is a big event with lawmakers in the capitol. Megan participated in a rare disease advocacy event organized by the Everrare disease weekylife Foundation for Rare Diseases that brought together over 300 rare disease advocates representing 48 U.S. states. The event featured speakers from congressional offices, pharmaceutical companies, and advocacy groups, including the National Organization for Rare Diseases and Research!America. The event gave the chance for Megan to network with other rare disease advocates and served as preparation for a full day of meetings with congressional leaders on March 1. There is so much to learn from other rare disease groups, many of whom have a much longer history and experience. We also value the chance to join together with them, using our larger numbers to influence policy and funding related to the FDA, the NIH, and other programs that could ultimately help advance treatments for rare diseases like KCNQ2. Together we hope to make them “Care about rare.”