Support group musings

Some thoughts below about a recent post on the Facebook page of the FamilieSCN2A Foundation - an online support group for parents of children with that genetic mutation. It's the one my daughter Haya has. 

Members of the group come from all over: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Denmark, Finland, France, Germany, Greece, Iceland, India, Ireland, Israel, Italy, Luxembourg, Malaysia, Netherlands, Norway, Poland, Portugal, Scotland, Serbia, Spain, Sweden, Turkey, UK, USA, United Arab Emirates, Venezuela. And probably more.

It was written by Carla Forbes, one of the group's administrators, and is about the FamilieSCN2A logo and the colors that feature so prominently.

This is what the SCN2A support group is all about and this is why the following recent post there grabbed my attention. 

First, to clarify: I only peruse the page occasionally. The posts aren't usually relevant to me as most of the children are both younger and higher functioning than Haya. Hence many of the posts just depress me. 

But all convey the sense that these parents are utterly devoted to their children and determined to provide them with every available therapy and treatment to improve the quality of their lives.

Then this week, while I was up in the wee hours caring for Haya, I read the post I mentioned. It was exceptional, jarring and disappointing - to me at least:

Well... we found a host family in Houston (a hour and 45 mins from us) that is interested in having Alyssa live with them full time. We meet them Saturday.  This is the hardest and loneliest decision we have ever made. No one gets it and not many have gone down this road..... its a hard road y'all. Praying this is the right fit but if not, we will keep looking.

Several readers offered supportive comments and another few "liked" it. I thought a loud "ouch" to myself.  

But then I noted that neither of the site's administrators responded, as they usually do. Their silence seemed telling. This page was obviously not the right venue for news of this sort. 

Here below is my daughter Haya at her latest Monday Hydro with Mom session. 

Next week the pool will be closed for repairs. So we will be relegated to the large, cold public pool nearby. 

Why have I not bought myself a wetsuit like Haya's yet?! 

As good as it gets

Happy birthday, Haya

I suppose it's time for an update on Haya's Keto diet and her epilepsy. I've procrastinated because there has been nothing good to report.

But today is Haya's birthday so the timing feels right.

We did finally achieve a ketone level which satisfied our dietician. But it wasn't accompanied by the greater seizure control we've been hoping for. She's still having around four big ones daily. She's also been having around an hour's worth of twitching every day. I've begun giving her Paracetamol to zap that. 

I sent a video clip of the twitches to the neurologist who responded that the Keto diet is ineffective against that symptom. And we may just be stuck with those four or so seizures every day. 

What is more disappointing, though, is that Haya hasn't shown any improvement in her functioning at all, despite the drop in seizure activity.

Worse, her walking has even deteriorated. Her stamina for it has diminished and since we can't have her feed herself Keto meals lest she drop or drip precious grams of the stuff, she's left doing nearly nil. 

Fortunately, she still floats and flips in the pool as well as she used to. But she used to kick occasionally and that's disappeared.

I've even put her Speech Pathology sessions on hold because they would probably be a waste of time and money. After two months of foot dragging, our health fund (the kupat holim of which we are members) finally decided on awarding us twelve sessions at NIS 123 participation per session. That means they are covering roughing half the cost.

For now I'm just persevering with Haya's walking. I even did it twice yesterday.

Eventually, we'll need to reassess the diet and decide whether it's really worth all the effort.

Along with this bleak reality came the following article [online here] via my Google Alert. It hails from "New paradigms for the treatment of pediatric monogenic epilepsies: Progressing toward precision medicine" by Nicola Specchio, Nicola Pietrafusa, Emilio Perucca and J Helen Cross. And published in the latest edition of "Epilepsy and Behavior"

And is it ever blunt and bleak.

It's laden with equally stark statistics about seizure control in children with developmental and epileptic encephalopathies (DEEs) which is what Haya has been "blessed" with.

Here's its opening paragraph:

"The past 30 years have seen the introduction... of over 20 second-generation antiseizure medications (ASMs). Despite this enlarged pharmacological armamentarium, seizures in about one-third of people with epilepsy cannot be completely controlled and outcomes are even poorer for certain syndromes, such as developmental and epileptic encephalopathies (DEEs)"

That's what Haya is "blessed" with.

"One possible reason... is that the large majority of currently available ASMs have been developed with the aim of suppressing symptoms (seizures), and were not designed to address the specific etiologies and mechanisms responsible..."

It goes on

"Treatment responses in SCN2A-related epilepsies appear to be more complex... for children with later-onset epilepsies [like Haya] sodium-channel blockers were rarely effective and at times even worsened seizures... patients with later-onset epilepsies [again, that's Haya] had truncating mutations, which were associated with lack of seizure improvement after administration of sodium-channel blocking ASMs."

And 

"For most of the severe DEEs... the overall prognosis... remains poor in terms of seizure control, intellectual disability, and other comorbidities."

There's even a chart which makes that bad news perfectly clear: For Scn2a Loss of Function Mutations in Nav.1.2 ASD/ID and Childhood-onset seizures, the chart bluntly says 

"We Do Not Currently Have Targeted Precision Treatments."

But hang on.

I may be stretching it but I believe I see a silver lining: It means that Haya's awful predicament probably isn't due to our having missed something. My husband and I aren't to blame.

Given the awful hand she's been dealt this is "As Good As It Gets". I know, I know, that's a small comfort - but a comfort nonetheless.

Happy birthday, Haya!

Embraced by the SCN2A community

Source: https://www.scn2a.org/

Last week I participated in a second Zoom session with other parents of children with the SCN2A mutation. As I've mentioned, we learned in August 2019, after 24 years of searching, that the underlying cause of Haya's disabilities is that genetic mutation.

The support group I've joined has nearly 700 member families from around the world. 

That Zoom conversation had six other participants. One from Kansas City, one from Massachusetts, one from England, one from Queensland, Australia, one from Germany. It was so interesting and edifying.

The two American mothers were involved with the formation of the SCN2A support group in 2013. So they had history to share e.g. when there were only a handful of members they concluded that the mutation must be limited to those with Irish/British ancestry, which they all had. 

That was debunked soon afterwards.

Next came the revelation that some children with autism have the mutation. Today, with US insurance companies funding genetic testing of autistic, most of the documented SCN2A children are afflicted with autism rather than Early Onset Encephalopathy Type 11 is which Haya has.

 
I also learned a bit more about the difference between Gain of Function and Loss of Function children. It seems that when epilepsy erupts later than the first few months of life, it's most likely that the child has Loss of Function, in which case meds that are categorized as Sodium Channel Blockers will exacerbate seizures. 

That would explain why Phenytoin, one such drug, only worsened Haya's seizures when we tried it several months ago. A neurologist familiar with SCN2A would have known that, since her epilepsy erupted at 14 months old, Haya is probably a Loss of Function child. 

Consequently, Phenytoin was a bad choice of med. But her neurologist has told us that she has no other SCN2A patients.

I recently acquired a list of Israeli doctors who have written articles related to this gene. (The parent from Germany who Zoom-chatted with us shared it with me.)

I intend to inquire whether any of them have clinical experience with SCN2A patients.

Me ZOOMing with the group

I also found out at that chat that research into gene therapy for this mutation has reached the stage of clinical trials on humans. It goes by the name Antisense Oligonucleotide Therapy. 

Unfortunately, if proven efficacious, it will only be beneficial to those who have Gain of Function. So Haya is out of the game.

Finally, it was inspirational to connect with other parents of profoundly affected children who have not institutionalized them, who continue raising them with love and devotion despite the challenges involved. 

I still vividly recall a neurologist advising me to institutionalize Haya when she was one year old! That same advice was repeatedly handed me over the years until she aged out of the educational system at age 21.

When will Israel abandon its archaic approach to caring for its most vulnerable children??? When will institutions like Aleh be shuttered???

In the meantime, readers, if any of you knows of an SCN2A child in Israel, please contact me!

How about some focus on SCN2A?

Image Source: PBS

Sadly, my daughter Haya's life hasn't been altered much by the Covid-19 restrictions. The parameters of her existence were extremely limited at the best of times. One exception was that weekly hour of hydrotherapy we used to give her at our local pool.

She is a superb back-floater, believe it or not. At least she was pre-Covid - and looked utterly relaxed throughout the session. She even smiled occasionally - her tiny tongue-poking-out sort of smile.

But it feels as though that happened in a previous incarnation. 

Now her only exercise is the 45 minutes of assisted walking I do with her religiously every night. I'm certain it benefits her too in myriad ways: respiratorily, cognitively, digestively. But it can't hold a candle to that water therapy. 

The pools are slated to reopen right after Shavuot. But I'm wary of bringing Haya back even then. While I haven't asked her doctors, I'd presume her genetic mutation and complex disabilities place her at high risk.

Speaking of genes, I just watched a magnificent 2020 PBS documentary, The Gene: An Intimate History which provided a history of the field and profiled several genetic breakthroughs that have transformed lives. 

It was both uplifting and depressing. The uplifting part I'm sure needs no explanation. But here's why it depressed me.  It highlighted the sad fact that Haya's mutation - SCN2A - has not benefitted from all those genetic advances.

From the series' website

I suppose the sparsity of her population is a crucial factor. There are under 1,000 documented SCN2a cases globally; Only 140 cases of the epileptic sort are born per 100,000 births. (There are additional cases where autism and intellectual disability are the symptoms.) Those numbers translate into minor financial incentive to pursue a treatment.

But the film relates the development of an astoundingly effective treatment for SMA, Spinal Muscular Atrophy, a genetic condition with about the same incidentce. 

Which begs the question of why SCN2A has been ignored.

Welcome to my SCN2A world

From a 2017 overview about the current knowledge
of SCN2A disorders, presented by Dennis Lal
of the Stanley Center for Psychiatric Research at the
Broad Institute of Harvard and MIT [via YouTube]

After a hectic period laden with stressful but (thank G-d) joyous events, I can finally refocus on this blog. 

First, to recap.

We now have a pretty firm diagnosis for Haya's symptoms after a 24 year hunt. 

While it is a de novo mutation of the SCN2A gene i.e. not hereditary (yay!), it has been an otherwise distressing discovery. That's because there is simply no effective treatment for it. 

The mutation causes a particularly severe and refractory epilepsy: Epileptic Encephalopathy Early Onset 11. It's sometimes called Early Infantile Epileptic Encephalopathy Type 11, and sometimes EIEE11.

Available anti-epileptic drugs are almost invariably useless, something we'd already concluded on our own after Haya's 24 years of relentless seizing.

Nonetheless, last month we brought Haya to a pediatric neurologist whom our geneticist had recommended highly. (She's booked up for the next year).

At that visit, she assured us she would study Haya's EEG's and her history and would then suggest medication changes as a first step. True, after the years of the med failures we've had, any new ones have no more than a 3% chance of success - but that isn't zero, as the doctor noted. 

So we all agreed it's the wisest first step.

Next, if we find Haya to be in the 97% majority med-wise, this doctor recommended we re-try the Ketogenic Diet. We had Haya on that diet some twenty years ago with minimal success and dropped it after 10 months because of serious, uncontrollable vomiting. 

 
But, as the doctor noted, we had had no professional guidance in calibrating the diet. So giving it a second shot with good medical intervention this time sounds wise.

If that diet fails again, she recommends going with a second VNS implantation. 

That was also a failure back in 2000 and we were bereft of sound medical guidance then too. So while I'm reluctant to subject Haya to surgery but if there's no alternative, we'll try it.

I also set up a Google Alert for the SCN2A gene and Epileptic Encephalopathy Early Onset 11. Not one of the journal articles I've been sent so far are relevant or helpful. Most weren't even about that gene! Are you listening Dr. Google?

Now a request.

The new neurologist, when I asked her, said she has no other patients with this syndrome. Our Haya, I think, may well enjoy the distinction of being the only such person in Israel.

If you know of anybody afflicted with it, please let me know. I will give you my personal details if requested in a blog comment.

At last - a pretty solid diagnosis

Let's hear it for the whole exome sequencing (WES) test and the Ministry of Health! (After all, it picked up the tab.)

After 24 years, we finally have a pretty solid diagnosis for Haya's symptoms; idiopathic has been officially deleted from our lexicon.

What was found is a mutation on the gene SCN2A. We learned the news in the geneticist's office which we entered and exited in 15 minutes.

A couple of weeks later, we received a more detailed summary of the findings which told us, among other things that a genetic variant was found which is designated VOUS or Variant of Unknown Significance on the gene SCN2A on Chromosome 2, exone 5

Mutations elsewhere on this gene are known to be the cause of Early Onset Epileptic Encephalopathy Type 11 (or EIEE11), a syndrome with symptoms identical to Haya's. 

While Haya's variant is on a spot where no other person is known to have one, the geneticists concluded that because 

"her clinical picture matches the clinical picture described in the EIEE 11 Syndrome, we are inclined to say that there is a high probability that the variant found in checking SCN2A which is described in the gene exome constitutes the cause of her illness... The laboratory in Germany that carried out the test concurred that the finding is a possible identification of the cause of her illness... It can be said with high likelihood that the parents and their offspring are not in any increased danger of a repeat of this anomaly in future pregnancies."

The geneticist recommended we consult a young local pediatric neurologist who might have some fresh treatment suggestions. She also promised to send Haya's file to a neurologist in California who is researching this very syndrome.

But trusty Google has provided precious little further info. We now know that this diagnosis is rare, still being researched and that at this point, no reliable treatments are known. 

We're hoping that one of those two new neurologists will help us. It's the nearly two and a half decades of clueless doctors that I've been vividly recalling. Clueless and arrogant.

There was the developmental pediatrician who was the first specialist we consulted. He summoned his entire staff at the Center for Child Development, which he headed. into his office one morning while he examined Haya. With utter confidence, he declared to his audience that she had been infected and damaged by CMV in utero. The trouble was, the blood test which I subsequently had proved him just as utterly wrong. I hadn't had CMV during my pregnancy.

That didn't phase the guy. Several months later, he declared to me with the same utter confidence that Haya had Rett Syndrome. At the time, there was no blood test to contradict that wild guess. But her then-neurologist pronounced it a false diagnosis. She didn't have any of the major symptoms, one being the "hand-washing" which had prompted Dr. Andreas Rett to classify this group of children as distinctive. 

A few years later, Israel's chief Rett expert examined her and declared that her gait indicated that Haya was indeed a Rett child. But when new blood tests finally appeared on the scene, they proved definitively that Haya did not have Rett.

I also recall another neurologist's declamation to me when Haya was about a year old: 

"She does not look like a child with a genetic disorder. It's not genetic." 

He also advised us to "send her away to an institution."

By now I'm sure it is clear why I am not a huge fan of neurologists. (You can read more about how I developed that distaste for them here: "A hospitalization journal".)

The silver lining to this bleak news is that the mutation is de novo. That means it wasn't inherited and, consequently, is of no concern to our offspring. Its de novo-ness was confirmed by doing the same whole exome test for me and my husband which proved that neither of us carries that mutation. 

One article I read posited that the most severe SCN2A cases are the de novo ones. A cloud in the silver lining?

One article that our son-in-law, a doctoral student of genetics, found us reports surprisingly encouraging results with unusual drugs. Conventional anti-epileptic drugs, it seems, actually exacerbate seizures for some Early Onset Epileptic Encephalopathy 11. 

But two drugs that are not intended to treat epilepsy were effective. Could that be why we find that Paracetamol helps her during a string of seizures?

In the meantime, here (above) is Haya showing slight progress with pushing her switch to play music.