New Answers

Here’s the scoop in a nutshell: Chloe, who has never had a true diagnosis, finally has a diagnosis! It seems that she has a mutation in gene EBF3 which caused a genetic syndrome that involves developmental delay and other characteristics. It’s a brand new find in the world of genetics so there’s not much to know other than that. If you want the whole story in a long blog post, keep reading…and sorry for the spoiler. 😉 And, now, for the rest of the story:

 

IMG_3511Earlier this month, we got a very interesting phone call from Chloe’s geneticist.  It seems it was possibly the most interesting news from her in …about 15 years. 

Remember that Chloe remains undiagnosed. Early on, neurologists and geneticists could not agree if her issues were genetic or neurological. Finally everyone agreed that it was genetic, but still there was no diagnosis. Chloe continued to see her geneticist each year, and if there were any new tests that had been developed over the last 12 months, then she was sent for those tests. But each test came back normal or inconclusive. Eventually, her doctors started calling it Chloe Syndrome since there were no answers.

Several years ago, Chloe did a whole genome sequencing and microarray study when it was first developed. It was a very smart, very high tech, very exciting genetic test that held a lot of hope for answers. It was a way to look at the very ends of genes and chromosomes to see if there were any smaller deletions or mutations. It was very expensive and wasn’t often covered by insurance. Chloe’s doctors jumped through many hoops to get the genome sequencing set up. The sequencing included extensive studies of Chloe’s blood samples and Paul’s and my blood. And the results took months to come back. But, again, in the end, these reports showed no answers and no diagnosis. 

A side note here in case you don’t know about the world of genes… through the years, syndromes and diseases have been identified, and many of them can be seen in gene studies. When a doctor tests to see if a person has a specific syndrome, the lab can be pinpointed to look at that specific gene to look for a mutation or a deletion. Likewise, if a mutation is found in a particular gene, it will sometimes lead to a diagnosis if that gene is associated with a certain syndrome. However, sometimes, a mutation can be seen in a gene, but it doesn’t lead to diagnosis because that gene hasn’t been associated with any syndrome and/or that gene hasn’t been connected to any disease or dysfunction. So, while Chloe’s gene sequencing showed a few abnormalities, the abnormalities were not of note because those genes had not been identified as being pathogenic (disease-causing). 

Fast forward to our phone call. Chloe’s geneticist had just received in the mail a letter from Baylor Medicine saying they had revisited Chloe’s sequencing because of a couple of very new studies and discoveries, and they thought maybe they had found the gene responsible for Chloe’s issues. 

Wow. We (and her doctor) were shocked. It was honestly never expected to ever find the cause of Chloe’s medical issues. It was hoped, yes. But even at our recent appointment at the genetics clinic, the doctor again explained that we likely would never have any answers. 

The letter pointed to one of Chloe’s genetic mutations and mentioned some recent studies that had finally linked this particular gene with some similarities in a very small group of patients. After some research, we definitely agree that this newfound information sheds light on Chloe’s issues. The similarities in the patients identified very closely resembles Chloe’s health history; thus, we have found the cause of Chloe’s genetic syndrome.

Sooooooo… the culprit mentioned in the letter…. the culprit that is the root of all of Chloe’s issues is a slight mutation in Chloe’s EBF3 gene. Never heard of it? Well, that’s because until very recently, EBF3 was not linked to any change of function or cause of disease so it has not been talked about. Until now.

Again, while the variance in EBF3 showed up when they first ran her genome sequencing a few years ago, at that time it was inconsequential because that gene had not been recognized to have any pathogenic effect. However, now they have found some clinical similarities associated with that gene. 

There are a small handful of articles that have been published in the last year discussing several studies surrounding EBF3 and a small number of patients who have a mutation. In fact, one of the studies from October 2016 includes 10 patients…”subjects,” if you will. And while I was reading the study, I was surprised to realize that Chloe was actually Subject 8 in that study! The subjects are never named, but there were several tell-tale details that made it clear that it was Chloe. Pretty cool that our girl was involved in one of the very first studies of patients involving this particular gene! (The unanswered question is why didn’t they notify the families a year ago that they were making some advances with a diagnosis….)

Through these research studies, the researchers determine clinical similarities between subjects who have the mutation. And with these similarities, they form a list of characteristics that most people with a mutation in gene EBF3 exhibit.

According to the research studies, it seems that patients with EBF3 variance have the following issues:

  • Low/weak muscle tone (Hypotonia)
  • Developmental delay
  • Balance/gait issues (Ataxia)
  • Expressive language issues
  • Urinary tract issues/ namely vesicoureteral reflux
  • Strabismus (eye muscle issues)
  • Weak facial muscles (inability to smile)
  • Autism-like symptoms
  • Repetitive muscle movements 

Shall I go on??? 

Amazing, right? It’s an exact list of Chloe’s issues. There is literally nothing mentioned in the studies that doesn’t ring true with Chloe! She has additional medical issues that are not on their list. But the truth is, some of those will likely be added to the list as doctors and scientists perform more studies with a larger group of patients. 

So there you have it. EBF3. 

It looks like currently there are maybe 30 people identified as having a developmental disability because of a mutation in EBF3. And it has been tagged with the name HADDS: Hypotonia Ataxia Developmental Delay Syndrome. The oldest person that I’ve read about is 25, and then Chloe is maybe the next oldest. Of course, this will continue to change as more individuals are identified. The patients have varying degrees of the characteristics. Some walk; some don’t. Some talk; some don’t. At first glance, it appears that Chloe has a more severe mutation than some, but, again, that may change as more is discovered about this population. 

So we have an answer. After nearly 16 years we have an answer.

But literally nothing changes. Chloe’s still the same Chloe. There’s no cure for her syndrome. There’s no new treatment to start. We simply know the gene responsible. And we know that it was a spontaneous mutation — not passed from either parent; sometimes mutations just happen.

But just like that, our family became part of an exclusive “club” that before now had declined our membership. The club of diagnosis. The club of EBF3 mutation. The club of HADDS. Of course, the families in our particular club are at this point still scattered about wondering what to do with the new information. I started a blog specifically to find and unite families who search the web for EBF3. I plan to post on it fairly regularly to keep Google in the loop for anytime someone searches EBF3. I found a Facebook page for families of EBF3. There are only 3 or 4 people in the group — this is still very new, and we are a very small population. But it was exciting to exchange greetings and photos with those families. Who knows? Maybe we will plan some sort of HADDS convention or something and hang with those families just because we can.

And that’s all we have. Thoughts??

Articles if you want to know more:

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5 responses to this post.

  1. Posted by Susan Bowman on October 27, 2017 at 8:01 PM

    This is huge! Congratulations!

    Reply

  2. Posted by Suzanne Byers on November 18, 2017 at 7:31 PM

    So excited to have found this blog! My son was diagnosed at the end of last year with HADDS.

    Reply

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