I was surprised when I visited this blog to discover just how long it has been since I have written anything here. Things have gotten busy and complicated, I just stopped finding the time to update. So, here I am with some updates to do. First Abigail, our youngest child was diagnosed with Autism and it was confirmed that she too has the same HIVEP2 mutation Brynn, Brett and I have. Abigail became the 4th person in the world known to have our exact mutation. She was also diagnosed with epilepsy this year, very mild compared to the boys. Wisconsin has still proven to be fabulous for Brynn and Brett, this is the best they have ever been seizure count wise. I am fairly sure at this point that the heat in the South may have been a factor all those years, and historically it makes sense that even Brett improved when we moved from AL to MO. My Epilepsy Warrior Boys are grown men now, 25 and 20 with beards most men in their 40’s drool over. They have leveled out cognitively, and matured nicely. Brynn still enjoys tinkering with things, and works part time at a local hardware store mixing paint. He has an amazing sense of humor and enjoys playing video games, doing anything working with his hands and helping people still makes him happy. Brett is pretty quiet, and writes song lyrics. He goes through phases of playing the drums, keyboard and guitar. He enjoys video games and streams games online and enjoys the thought of making people happy. Things not only got busy, they also became intensely complicated as Brett was diagnosed with schizophrenia last year. This was a known risk, as I had spent two years intensely researching the boys genes to try to find the cause of their seizures and intellectual disabilities. I think back to those years and wonder where I found the brain power to do that now! I did learn a lot about their health risk, running their raw DNA through programs, researching all the genes and tracking down which ones they both carried analyzing to see if seizures and/or intellectual disability was part of the disease risk involved way back in 2015-2016 before most people even knew it was a thing. I remember I was scoffed at when I took the pages and pages of data I had accumulated to the geneticist, the geneticist said that they could not go by that data. Yet, even today when you look at the rare disease gene that the WES test ended up identifying as the cause, it gives a SNP: RS1774991184. If you are curious, my method was downloading the raw DNA for Brett, Brynn, Mother (Self) through 23&me.com and ancestry.com. I then loaded raw DNA into Enlis, then uploaded into Enlis Genome Personal 1.8 Software as well as Promethease Software. Used SNP’s that I found from Enlis to obtain more information through Variatas. I still have hundreds of pages of files that list SNP’s that Brynn and Brett have in common. Ancestry and 23&me only are giving a tiny bit of dan information, nothing compared to a Whole Exam Sequencing test, which eventually brought us to the diagnosis. I am surprised looking back that I survived that intense research that did nothing more than give me so many more things to worry about them possibly having. I did learn though, that they both had unusually high markers for schizophrenia, which to my knowledge no one in the family had been diagnosed with before. I also saw risk for Autism, Rhett’s, EDS, ALS among many other diseases. Genetics is a fascinating topic to explore, especially when in context to symptoms being experienced. One may have a few or thousands of mutations that may cause disease, but diagnosis happens when disease symptoms are present. In our case, HIVEP2 is Ultra Rare, having only a few hundred cases known worldwide. That in itself makes for complications when knowing whether a particular symptom is that of the mutation of coincidence. For Brynn, Brett, Abigail and I we are rare, in that we are the only four people in the world with our exact mutation. I have read just about every scientific paper written on HIVEP2, but I have yet to see chronic pain being a symptom listed. Some studies suggest that HIVEP2 can have a broader impact on the nervous system, perhaps affecting pain perception and sensitivity, which sounds a lot like the “Fibromyalgia” I was diagnosed with back in 1999. Brett and Abigail have a blood clotting disorder and to my knowledge that has not been seen in HIVEP2 as of yet. Most studies list muscle weakness and hypotonia but not pain, yet us four certainly all have it. Deletion of HIVEP2 in mice leads to schizophrenia-like behaviors and neuropathological features. This suggest a link between HIVEP2 and the schizophrenia. There is a Dr. in Chapel Hill, NC who was running a study on HIVEP2 and schizophrenia, which was interesting for Brett, I tried without success to reach out to him. When the boys received the diagnosis back in 2016, all I could find was intellectual disability, possibly seizures and hypotonia. Most studies now are expanding to list cognitive and social impairments, anxiety-like behaviors, hyperactivity, memory deficits, hypotonia, developmental delay, intellectual disability, language impairment, reflux, strabismus, impaired speech, anxiety, autism spectrum disorder (ASD), mild structural brain anomalies, mild dysmorphic features and seizures. I suspect that in my lifetime I may eventually see the chronic pain become part of the syndrome as well. If a non related person or persons would become diagnosed with the same mutation and similar symptoms, then we would have our own unique “flavor” of HIVEP2, which we indeed do already, you’re not going to find us in any papers anytime soon by the looks of things. It is interesting to ponder what a specialist proposed, that our specific variant may be more severe in males, with seizures and intellectual disability being moderate and females having more mild seizures and autism. Specifically, us four share the anxiety, GI symptoms, muscle weakness and pain but we are different in the cognitive and seizure diagnosis. The Rare Disease organization that sends out yearly behavioral and health assessments isn’t even using the data from most of the inherited families that are participating from what I can tell. I recently submitted the assessments for the first time in a few years, so I guess we’ll see if the numbers change having just added the three siblings with seizures to their data. We are just chugging along, knowing that in reality we are writing our own unique book on our rare journey. I suspect that it may not even happen in my lifetime, that we have more insight on our variant. I haven’t given up hope though. I don’t give up, if I did we wouldn’t have made it this far would we have? In the meantime, I will try to update here every few weeks or months. Someday, someone with our variant is going to come across this blog and be so grateful to have found their tribe.

~Denise