We have had two specialist appointments this week, and both have come back with abnormal findings. Yesterday, we saw a pediatric opthamologist, who discovered that Curren was mildly far-sighted with astigmatism. He was also diagnosed with esophoria, a condition where his eyes tend to move inward, especially if one eye is covered. This most likely results from his generalized low muscle tone, and it is not severe enough to require glasses (I can only image how unsucessful attempting to wear glasses would be at this time in life!). Today, Curren visited a cardiologist for the first time. His EKG resulted in "boderline" abnormal findings. They found that he has a polarization abnormality in the electrical charge just before his heart beats. He had a echocardiogram following these results, which made the cardiologist feel pretty certain there were no concerns at this time, which is fantastic news.
I am grateful that we so often receive "mildly" abnormal results, but it is a bit nerve racking to always have abnormal findings. EEGs, swallow studies, MRIs, growth parameters, metabolic testing - all of these things have come back abnormal, but not severely enough to warrant any action. It is now clear that abnormal has become the new normal. This is my son, he is not like any other, and I love every inch of his "unique" self.
We also had the amazing opportunity to be seen by genetics and neurology at Massachusetts General Hospital in Boston last week. Our experience was incredible, and we left with lots of optimism about Curren's potential, We also provided skin biopsies, for the potenial hope of doing stem cell research and creating patient derived cell lines for further study of HIVEP2 disorder. Another perk on the trip included the chance to meet one of our newest HIVEP2 families from Boston and the author of the first HIVEP2 paper for dinner. Our tiny universe is expanding, and I am so excited for what the near future holds.
My family is on a journey I didn't expect to take, and a foundation of hope has been my north star. Our journey can be inspiring but also many times daunting, and if we become hopeless we will lose our way. I would like to honor my son by sharing his brave journey.
Curren has been seen by 5 neurologists, 4 geneticists, a neurogeneticist, 2 developmental specialists, a GI specialist, an ENT specialist, 2 ophthalmologists, a orthopedist, 2 orthotists, a podiatrist, 2 psychologists, 2 pediatricians, 4 physical therapists, 2 occupational therapists, and 2 speech therapists - this has all been in the first 3 years of life. Beginning about 2 years ago, Curren ramped up therapy to 5 days a week, sometimes up to 4 hours in one day. He is a tough cookie, and he works very hard every day. Sometimes he forgets how to do the things he learns, but Curren never gives up.
Curren was born with a mutation in his HIVEP2 gene, but he was not diagnosed until he was 2 years old, after a long diagnostic journey. When reviewing his birth records, I noticed they recorded abnormal hypotonic behavior and muscular tone upon his first evaluation, but it was actually Curren's daycare that told me his muscle tone was not normal 4 months later. Between his low tone and difficulty with brain signaling, Curren has a very hard time controlling movement, especially in his legs. And although his muscles are strong enough to do it, Curren hasn't been able to crawl, pull up, or walk yet. He is, however, doing fantastic in his new wheelchair, and we are planning to get a mobile stander which supports Curren in a standing position but has wheels like a wheelchair so that he can move around and be at the level of his peers. Many people ask if Curren will ever walk, and it's a challenging question to answer. There is no way to know, but I have hope that he will.
We have been very blessed with good health over the past year, but that wasn't always the case. Curren was first sick when he was 4 weeks old, and was on antibiotics over 20 times during the first year and a half of life. He was diagnosed with reactive airway disorder at 4 months old, when he was in the hospital for respiratory distress. Curren also experienced a seizure and metabolic crisis event when he was two. Many of the other children with HIVEP2 disorder experience GI issues, but the only problem we have experienced is a failure to thrive diagnosis based on Curren's slow growth. We are also very fortunate so far to have good reports from the ophthalmologist, as eye problem are common for our community.
Perhaps one of the most challenging aspects of HIVEP2 disorder is the developmental disabilities. Like many others, Curren was diagnosed with autism, although he is actually very motivated by social experiences. The features of autism that Curren displays are regressions, language disorder, sensory integration disorder, and obsessive compulsive disorder. Curren is non-verbal, and it is so difficult for a child who has so much to say to not be able to say any of it. He understands what it going on around him, and he has intent for his legs, hands, and mouth to do certain things, but the message seems to get scrambled and the action doesn't happen the way it should. Lately, I ask Curren to touch his head (which is actually very challenging for him since he can't see it) and he starts clapping. I can tell from the look on his face that he is not thinking about clapping and is confused why his hands aren't touching his head, but the directions from his brain don't seem to be delivering the right message. I see this also in his speech. Once when we were in the hospital, and he was over it. He said clear as day "all done", but hasn't said it again in over a year. I can't imagine the frustration to have this disconnect between your brain and your body, but my son handles it incredibly.
On this journey, we have seen such kindness and compassion. It is so heartwarming to see Curren's fans, rooting for him to not give up. Curren has an exceptional team of professionals caring for him and looking for answers. We are eternally grateful to the doctors and therapists that are making a difference in Curren's life. It is not always an easy journey, but the people that support Curren do make hope feel more grounded. I am also so very proud of my son for the tremendous effort that he puts forth, and for his beautiful spirit that has not been subdued. I have hope for the future and what it holds!
From Autism Spectrum News - Winter 2017 Issue
By Emily Singer
By the time her son Curren was 3 months old, Nerissa Ramsey knew there was something different about him. He had low muscle tone and flapped his hands. Hand-flapping is a repetitive behavior commonly seen in autism.
After consulting with a series of specialists, the Ramsey family was referred to a geneticist. The standard test for developmental delay — chromosomal microarray analysis— looked normal. So did other genetic tests the doctor ordered over the next year and half.
Curren, meanwhile, began to regress. He lost the handful of words he had begun to use at 12 months. He also stopped using the signs he had learned for “more” and “eat.”
When Curren turned two, the Ramseys decided it was time to try whole exome sequencing. This is a genetic test in which scientists decode the portion of the genome that corresponds to proteins. Exome sequencing is often used in genetic research. But it is still fairly new as a tool for clinical diagnosis.
Few families with an autism diagnosis will be referred to a clinical geneticist. Fewer still will be offered exome sequencing. Curren’s severe symptoms and negative results on other tests made him a good candidate.
Four months after submitting their son’s DNA sample, the Ramseys finally got the answer they had been searching for. Curren had a mutation in a gene known as HIVEP2. This gene is involved in brain development.
The condition is incredibly rare. When Curren was diagnosed, only three other children with mutations in HIVEP2 had been reported in the scientific literature. All of them had developmental delay, intellectual disability and muscle weakness.
Scientists know little about the effects of the mutation. And no treatments exist for HIVEP2 mutations. But the diagnosis was a relief to the family. Nerissa said that just knowing about three other children with the same genetic condition was helpful.
The family’s geneticist was optimistic when delivering the results. She noted that all three children eventually learned to walk and talk, meaning that Curren might one day as well. “That helped a lot,” Nerissa said.
The diagnosis also gave the boy broader access to certain tests and treatment programs. “If you can put a name or reason behind what is going on with your child, it opens so many more doors,” Nerissa said.
A Growing Network
As soon as the family learned of Curren’s mutation, Nerissa reached out for help. She blogged (http://nerissaramsey. weebly.com/) about the diagnosis and asked friends and family to share the post. She began researching the gene. She wanted to understand its biology and how the mutation worked.
In April 2016, a new paper on HIVEP2 popped up (https://www.ncbi.nlm.nih. gov/pubmed/27003583). It described six additional children with mutations in HIVEP2, including Curren. (The Ramseys had given their geneticist permission to publish his information.)
Nerissa was thrilled to learn about the additional families with the same disorder. And she reached out to the study’s senior author, Dr. Wendy Chung. Chung is a clinical geneticist and scientist who leads SPARK (https://sparkforautism.org/portal/ page/meet-the-staff/).
At Chung’s suggestion, Nerissa enrolled in the Simons Variation in Individuals Project (VIP) (https://simonsvipconnect.org/). This is an online community that supports families with rare genetic changes linked to autism and developmental delay.
Through the VIP, Nerissa and Chung set up a virtual conference for HIVEP2 families, which took place in December 2016.
Connecting with other families has been extremely helpful. “When dealing with such an ultra-rare diagnosis, most doctors have never heard of it and are not that interested in learning more about it,” Nerissa said. “The family community is probably the strongest resource we have, short of Dr. Chung, who has taken us under her wing.”
Nerissa and some of the other parents formed a family support group. “So far, three families found me through social media and my blog, outside of the families that have currently been published,” Nerissa said.
Most of the children in the group are older than Curren. So the Ramseys can learn from them about what to expect. For example, more than half of the children in the group have severe vision problems. “So I am monitoring Curren’s vision and taking him to see an ophthalmologist more often than I would have, had I not had that information,” Nerissa said.
SPARK hopes to provide other people with autism and their families with a similar chance to learn about genetics and connect with other families. People who enroll in the project will have the chance to have their exome sequenced.
However, SPARK’s genetic analysis differs from that of commercial sequencing services, such as the company that analyzed Curren’s exome. SPARK is starting by focusing on a fairly narrow set of genes — including HIVEP2 — and mutations. The ones the project is looking at have strong evidence of a link to autism. These genes have been identified in multiple studies, all in more than one family.
One of SPARK’s goals is to aid in the discovery of additional autism-linked genes and then add those genes to the list of results to return to families who wish to see them.
Chung cautions that not everyone who has his or her exome analyzed will get an answer to the cause of autism in their family. SPARK scientists estimate that sequencing will detect an autism-linked mutation in roughly 10 to 15 percent of participants.
In the meantime, SPARK provides many other chances to participate in important research that will enhance the understanding of autism. Indeed, Chung’s goal for SPARK is to create a community where researchers and families can connect in useful ways.
“This is about trying to make the process more efficient and more inclusive, so that people who have historically been left out of the research process can become involved,” Chung said.
For the Ramseys, getting a genetic diagnosis and connecting with other families has had a powerful impact. “My ultimate goal is to accelerate research,” Nerissa said. “If you can find a community, whether it’s two or three families or thousands of people with the same diagnosis, there is strength in numbers.”
Today we simply don’t know enough about autism. SPARK—a landmark autism research project—aims to make important progress possible. SPARK stands for “Simons Foundation Powering Autism Research for Knowledge,” and the mission is simple: we want to speed up research and advance our understanding of autism to help improve lives. If you or your child has a professional diagnosis of autism spectrum disorder, learn more about SPARK by visiting https://sparkforautism.org/.
My son Curren has magical blue eyes and beautiful red hair, which happens to be the rarest eye and hair color combination in the world. But making him even more rare is the genetic disorder he has been diagnosed with. While the numbers have grown since last year's diagnosis, he is currently only one of twelve know in the world with a disease-causing mutation in a gene called HIVEP2. There are not many resources available at this time, and the current management approach is to treat the symptoms, which often include intellectual disability, autism, seizures, sleep disorders, vision problems, speech delays, movement disorders, and developmental regressions.
It has now been a year since Curren's diagnosis - a year filled with soaring highs and defeating lows. Managing a life-altering diagnosis has been overwhelming, and has brought about some striking juxtapositions. I have somehow become both stronger and more fragile at the same time. We have developed an amazing support network of therapists, teachers, and case managers, and yet somehow we feel increasingly isolated. I find myself outwardly expressing a steadfast optimism, but internally I have felt unease since the day of the diagnosis and every day since. I question what more can I do with the waking hours I have, and when will it be too late to make a difference? It is a heavy weight to carry, and the uncertainty of not knowing whether there may be a potential treatment that would improve my son's quality of life if ever available is heart crushing.
As we have navigated this past year, I keep searching for places where there are more children like Curren, and surprisingly, we keep coming up short. At the early intervention center, Curren was the only child in the program who couldn't walk. He is one of the only non-verbal children in his new special needs preschool, and there are no other children in wheelchairs. Some of the specialists we see just toss their hands up with no recommendations and say "see you again in 6 months". Not only is Curren developmentally delayed, but his physical appearance and size is much more like that of a young toddler, so strangers usually refer to him as a baby and are flabbergasted if I tell them he is three. And that leads to perhaps my biggest worry. Curren is a very social child, and he adores interaction with others. He works so diligently to get people's attention and to get them to smile and wave to him. It incredibly charming right now, because he is perceived as a bubbly little baby with a contagious grin. But how will the world treat him when he is 7, 16, or 30 years old and no longer a cute small child? Curren has differences in his brain which cause him to take him longer to react and respond to people, but his intent is there. Will he be left in the dust in this world as our society becomes more impatient and focused on instant gratification?
Through the challenges, a new perspective arises, and it is clear that being a caretaker and an advocate for a child with special needs brings life to a whole new level of richness and beautiful complexity. The emotion that is felt when hearing your child's sweet voice say "mama" after 2 years of trying is indescribable. Watching your son break down in frustration every day for weeks upon weeks makes that giant belly laugh seem like the bees knees. The dark does not destroy the light, rather it defines it. Life is enriched by difficulty, and I am honored to be chosen for this journey.
-Climb mountains not so the world can see you, but so you can see the world-
Today Curren had his 6 month recheck with our local geneticist. This is the first time we have been back since we received Curren's HIVEP2 diagnosis. I think back to those first few weeks that were spent trying to wrap our heads around the information we received, and I quickly threw together a post describing everything I knew at that point (which was not much at all) - without a plan, but hoping to get something to stick. We were given a diagnosis that only 3 others in the world had, and none of our doctors were even familiar with the gene. I scoured every PubMed article I could find that seemed relevant, and blasted emails to dozens of doctors and researchers each weekend. I felt guilty as I mourned the loss of the child I had imagined, and tried to cope with the reality of our situation.
Today has a very different perspective. It feels like we are light years from that moment 6 months ago. We have accomplished so much in such a short period of time, and the future is looking bright. My mind is blown at these incredible advocacy milestones that have all happened in a matter of months. Curren has been medically published, we have 2 amazing community fundraisers going to support HIVEP2 children, I have found 2 other wonderful mom's of children with HIVEP2 disorder, we have an incredible research-driven doctor starting biological lab studies on HIVEP2, Curren's story was published here and here and here, but best of all Curren is healthy and happy and loved so dearly! Thank you to everyone for all the love and support. We really are climbing mountains and getting a better view (and starting to stand on our own with very minimal assistance from dad!)
The Rare Disease Day 2016 slogan ‘Join us in making the voice of rare diseases heard’ is a charge for everyone to join the rare disease community in making known the impact of rare diseases. I am happy to share Curren's story, in the hopes that his voice helps to bring about change!
Curren’s first few weeks of life started out calm and beautiful. But he caught his first cold when he was 6 weeks old, and was perpetually sick for the next year and a half. We went to the ER at 4 months old due to respiratory distress. Shortly after, Curren was diagnosed with failure to thrive due to weight loss. Over the next few years, Curren’s growth and development remained stagnant as we desperately tried to pinpoint the reason behind his delays and regressions. We experienced incredible highs and heart-breaking lows, but mostly we felt isolated and alone. Eventually we arrived at an answer. Curren has a single-point mutation in the HIVEP2 gene that is predicted to affect brain growth and development, immunity, hormone production, and bone remodeling.
There is one other child in the US currently known to have a HIVEP2 loss-of-function mutation - our friend Ryann. Because our voice is so small, we have not found much in the way of understanding our diagnosis, or possible treatment/management options. We have no information about prognosis. The response from most doctors or programs is one of two: (1) You already have a diagnosis, we are here to help the undiagnosed, or (2) There is nothing more you can be doing to help your child. I can't accept the second response.
I have been doing research on the HIVPE2 gene function, and have found affected pathways that are also compromised in more well-researched syndromes that currently have treatment trials underway (Phelan-McDermid Syndrome SHANK mutations and HIVEP2 both affect SSTR-2 function, Rett Syndrome gene mutations and HIVEP2 both upregulate the NF-kB pathway, increased MGluR5 signaling is common to both Fragile X and HIVEP2). My biggest hope for the future is that a more comprehensive approach can be taken with rare diseases. What if one of the treatments for a more well-known disease could benefit Curren and Ryann (and possibly many others)? I spoke with the doctor overseeing the Phelan-McDermid and Autism Specrum Disorder IGF-1 clinical trials regarding the common pathways I had found, and if he thought that IGF-1 treatments might benefit Curren. The response was that it was likely, but we don't meet the criteria for any of the trials, and the IGF-1 treatments currently cost over $100,000 a year.
I am in awe of the advancements in the field of clinical and scientific research, but I wish there was a quicker way to apply broad findings to specific cases. It is heartbreaking to see Curren break down in frustration due to his current limitations with communication and mobility. I want so badly to give him every opportunity to be able to express himself and move independently. My mission is to keep my son happy and healthy, and I believe that will be best achieved through accelerating research and raising awareness.
My hope is that World Rare Disease Day brings a new level of awareness to a critical issue. More people are affected by Rare Diseases than cancer and AIDS combined, but many with Rare Diseases have no resources, support groups, or research opportunities. Please help Curren's and Ryann's (and all the beautiful others) voice be heard by sharing our story!
The past 3 weeks have brought lots of new and exciting changes. We did intensive movement therapy last weekend, and are now seeing a very noticeable difference in Curren's motivation to move. He went to the Connectivity Center in Melbourne for Anat Baniel Movement Therapy (ABM therapy) in the morning and afternoon for 3 days. The therapy was different than anything else we have tried - it was very much on his terms. So he decided what he wanted to do, and the therapist helped facilitate the movement. The philosophy is that the movement becomes more hard-wired in his brain if he is the one that initiates it. So overall, lots of kneeling, reaching, rolling, and scooting through play - with an emphasis on posture and body placement. Curren worked so hard and we are very proud of him! For the first time, he is now consistently pushing up from his tummy to hands and knees, and the sitting down. This is huge, as he had always been stuck on his tummy (which caused lots of frustration!)
Curren is also making great progress with his goals in his traditional therapies. He is making new sounds at speech and becoming really fantastic at mimicking. He has been working in the spider suit, which is a belt and bungee system that provides enough support for Curren to stand and bounce. He has been working on various activities in the spider suit with a rope in front of him - unclipping clothespins, throwing a ball over the rope, and hanging on for support while jumping. He was also trying to say "up" when he was throwing the ball. Working on PT, OT, and ST all at once!
We also just started new therapy at the Scott Center. It's called Applied Behavior Analysis therapy, and we are going to focus on communication, expression of wants/needs, reducing distractions, and overall socialization. His therapists seem very sweet, and Curren really seems to like them a lot. His weeks are pretty jam packed with activities now, but all of these services seem to be making gains in forward progress, and we are so thankful for all of the help that Curren gets.
It was almost 3 weeks ago when we went to Kennedy Krieger and the Children's Hospital of Philadelphia. (And I am so glad we're not up there right now in a bliazzard!) It was a super busy trip - we stayed in 3 different hotels over 4 days. Curren was a rock star the whole trip. He was so happy, and loved everything - the plane, the elevators, the hospitals, and the arctic-freezing cold air. The best part about the trip was the wonderful people we visited with. There is only one other child in the US currently known to have a HIVEP2 mutation, and we were so fortunate to meet her and her sweet mother. It was helpful for me to find another on this journey that feels overall rather lonely. In the context of things, our children are one in a billion, and it's not easy to spark medical interest with those odds. Needless to say, the visits with the doctors were not what I had hoped for. I was impressed by the effort Kennedy Krieger put forward. At one point, there were 5 doctors in our room, listening to me trying to summarize a medical record that is thousands of pages long in 15 minutes. We found out there are structural abnormalities in Curren's brain they observed by reading his MRI from when he was 9 months old. He has a thinning corpus callosum, which connects the left and right hemispheres of the brain, and delayed myelination (immaturity of the plasma membrane that allows nerve impulses to move quickly). This was really about the extent of the beneficial medical information we got from our trip.
The other really wonderful part of our trip was a visit with a very old family friend in Philadelphia. We visited with a beautiful soul who played an important part in my childhood, and I haven't seen her in over 20 years. It is so great to have those people in life where decades can go by, and yet it feels like time has stood still when reunited. It was truly amazing to see our old friend.
The director of clinical genetics at CHOP told me something that put things into context. She said that Curren is a pioneer, and is just writing the beginning of the story. When we got a diagnosis 3 months ago, I started a crazy midnight googling effort. I have reached out to over 50 different doctors, hospitals, research programs, and clinical studies. We got appointments with 2. We have been rejected time and time and time again. When I got some interest from someone followed by a rejection, it shattered me each time. I had hopes that there was some type of medical intervention that I didn't know about that would improve Curren's life. I am realizing now that there is just incredibly limited information available about this gene and the effects when it doesn't work properly. A rare or orphan disease is defined by a condition that affects fewer than 200,000 people in the United States. Right now, HIVEP2 mutations affect 2. We are dealing with an ultra-ultra-ultra rare disease, and there is simply a lack of information available. It's not the answer that I hoped for, but I am at peace with it (and that was not easy). I am going to focus my energy on what I do have control over - providing quality therapies, feeding this baby uber-nutritional food, living in the present, and celebrating the awesomeness that Curren is!. Love this boy!
A lot has happened in the past week or so. First, I can't even begin to explain the overwhelming support that my family has felt since we received the news of Curren's rare genetic syndrome a few weeks back. There are so many awesome people in this world, so thank you to all from the very bottom of my (exhausted) heart! There have been many ups and downs this week, and I want to share with everyone the good, the bad, and the ugly (but especially the good)....
The incredible news is that we have been able to make an appointment at Kennedy Krieger in the Neurogenetic Clinic to see two of the doctors that contributed to the recent medical publication on HIVEP2 mutations. There is a fabulous person that helped us get our foot in the door, and lots of recommendations from people to start there. We are beyond excited to talk to doctors that are familiar with researching HIVEP2 mutations. We are also trying to set up appointments at Johns Hopkins that would coincide with our visit to Baltimore. Fingers crossed....
On the topic of good news - here's a bunch more. Curren had his 6 month re-evaluation this week with Early Steps and he is going to be authorized for an additional session of speech therapy and occupational therapy a week. We are really looking forward to the extra help! Curren also had an appointment this past week to have new orthotic braces made, which is fabulous news because it means his feet are finally growing. We were also assigned a case manager through our insurance company this past week. She seems super fabulous, and I think she will be a great asset to us - as we very frequently have claims denied, and some of Curren's very best therapists and specialists are out of network and currently not covered by insurance. And we also had a initial appointment with the Scott Center for Autism this week. We're hoping that the behavioral therapy they offer will become available to Curren to help with some of his frustrations.
So, on to the not so good - we got a call from the preschool the other week that they were afraid Curren was having a seizure. He was playing in the gym and just fell over. His body went completely limp and he had a staring spell for a few minutes where he wasn't able to focus or look at anyone. On our pediatrician's recommendation, we took Curren to the local ER, where we had some really good, and some really not so good experiences. What we found out was that Curren's blood sugar was at 40 when we arrived. He also had very low CO2 levels, and was diagnosed with acidosis (his metabolic pH level was more acidic than it should have been). They had an awful time getting an IV in his body, and from this point began blood sugar monitoring every 1-2 hours (which was also awful, but necessary). Curren did magnificent in his CAT scan, he laid completely still as a statue, and the results of the scan were normal. The local hospital got in touch with our Neurologist at Nemours, and the verdict was that we needed to be there. Curren was transported by ambulance to Nemours, so that he could be in the best hands at the children's hospital.
It was great that we were in such good hands. What wasn't great was the fact that people kept coming in to our room every 30 minutes or so, usually to poke Curren. And when there weren't people in the room, his alarms were going off every couple minutes or so. I don't think either one of us got more than 15 consecutive minutes of sleep through the night. Curren began an EEG in the morning, to see if any more seizure activity could be recorded. His CO2 and blood sugar slowly stabilized throughout the day, and we saw no seizures. There was, however, a new area of his brain that showed seizure-like activity - this time it was his left temporal area (in addition to his left occipital area). At the end of the day, everyone decided that all the numbers were stable enough and we could go home. This was fabulous news, considering Curren was basically miserable in the hospital - between all the wires and the constant pokes, he was completely skeptical of everything and everyone in the hospital.
So on to more good news - we followed up with our pediatrician after the hospital stay and Curren's blood sugar was perfect. We don't really know if a seizure triggered low CO2/acidosis/low blood sugar, or if low blood sugar triggered a seizure. But either way, things have been much better since the hospital. We have been feeding this guys every 1-2 hours to be on the safe side, and things have been great.
Aside from the hospital encounter, it hasn't been the most wonderful of times. I am still trying to wrap my head around the genetic diagnosis we received a few weeks ago. I have been googling my brain out, and reading some scary things. I wish that life could go on hold for a few hours (or just maybe a couple minutes?) so I could get a chance to catch my breath and focus, but there is a 2 year old and a 6 year old, and a +full time job, and laundry, and a gluten-free/dairy-free diet prep for the week, and homework. I don't know what the future will hold. Will my littlest require 24-hour care for the remainder of his life? Based on the information I have today, it's probable. Do his genetic condition predispose him to some nasties? Seemingly so. But I have a fabulous smiling face, and that's truly all I need. I will go to the ends of the earth to find options to allow him to be his personal best. And that's the next chapter...
This past week, we received information about Curren that is both hopeful and heartbreaking at the same time. My very first post touched on my anxiety over the unknown, and with this information now comes a whole new level of anxiety. Curren’s Whole Exome Sequencing genetic testing results came in, after over 4 months of (very anxiously) waiting. The test was denied by insurance, on the premise that it wasn’t medically necessary. Whole Exome Sequencing typically has about a 25% chance of providing meaningful results, and in our case, we were told it would be closer to 35%, due Curren’s severe developmental delays. Since the coverage was denied by insurance, I didn’t expect to get the results. And even if it were to be analyzed, the odds were greater than not of getting useful information back….and yet somehow we did.
We found out that Curren has a variant (D397Y) in his HIVEP2 gene that is most likely causing severe developmental delays and chronic medical problems. It is incredibly rare – according to GeneDx there are only 3 others in the world that are currently known to have a HIVEP2 variant, and each of these individuals have unique variants. The clinical features of HIVEP2 mutations are moderate to severe intellectual disability, developmental delay, autism spectrum disorder, easy fatigability, and hypotonia (low muscle tone). The HIVEP2 gene's function is very complex - it is responsible for regulating the activity of about 25 different genes that control brain growth and development. My son’s variant is predicted to be damaging to DNA structure and function, resulting in loss of function in the brain. Other functions that seem to be affected are cell immunity, brain signaling pathways, pituitary hormone production, bone remodeling, and memory. All of this from one misspelling in a series of 2446 amino acids, in one gene of over 20,000. It is just a tiny mistake in the grand context of things, but so significant to the overall function of the brain.
There have been recent lab studies on mice where the HIVEP2 gene has been made inoperative, and the results were brain inflammation, memory deficits, and hyperactivity. The mice were treated with anti-inflammatories and other trial medications and some of their neurological features improved. I have hope that therapeutic options like these may eventually become available for Curren.
Curren is now two years old, and has many severe deficits. He is not able to yet crawl, speak words, or communicate through signing, gestures, or pointing. He has been sick for more of his life than not - I tallied up the courses of antibiotics he has been on, and it has been 17 times in 25 months of life. He is in the 1st percentile for height, 3rd percentile for weight, and 7th percentile for head circumference, despite a modified high-calorie/high-fat/high-protein diet. He is in 8 hours of therapy weekly, attends an early intervention preschool part-time, and his daddy now stays home with him to do lots of one-on-one work and bring him to all his appointments.
Above all else, my most important job in life right now is to be Curren’s voice. I want the world to know just how important my son’s development is. It is heartbreaking to see him master a simple skill (like waving a month ago) and then lose it. As incredible as it was that he crawled on his hands and knees with assistance a few weeks ago (accomplishments!), he has not been able to do it again since. My hope is that our therapeutic options don't end here. With the new information we now have, I want my son to have the opportunity to see doctors and researchers that have an interest in pursuing management and treatment options tailored to his unique challenges. I know that there are (incredibly smart) people in this world that would be very interested in researching this further, we just need to find them!
If you are reading this post, could you please help Curren and share this information with the world? My biggest hope right now is that his information will somehow fall into the hands of the right person. We are willing to travel anywhere to find someone interested in helping my son overcome/manage his biological barriers. Thank you all so much from the very bottom of my heart.
I have been living with anxiety off and on over the past year and a half. I am not an "anxious" person, aside from the occasional butterflies in my stomach when I speak to a crowd. And I don't know that anyone that sees me on a regular basis would believe me if I told them that I've got some pretty extreme anxiety right now. This is the keeps-you-from-sleeping, feels-like-you're-hanging-on-by-a thread, body-is-aching-from-being-tense type of anxiety. It has been slowly building and comes and goes, but has pretty much culminated into the perfect storm over the past few weeks. My mind does not really ever rest. As a mother of a young child with undiagnosed medical and developmental complications, I can't stop searching for information in hopes of improving my son's situation, to the point of obsession. This has absolutely nothing to do with anything in my life, other than the helplessness I feel about our lack of medical progress over the past year and a half. It is a pretty awful downward spiral of a place to be.
We are 4 months into our wait for Whole Exome Sequencing genetic test results. The Whole Exome Sequencing is basically the mac daddy of genetic testing - it looks at over 20,000 genes within the human genome, where 85% of mutations known to cause diseases reside. I would be slightly less anxious had Cigna not denied the claim, on the premise that it is not medically necessary (separate rant...) I was told by a very unhappy and pretty uncertain-sounding woman from the genetics lab a few months back that as far as she knew, they were still moving forward with the analysis despite the insurance denial. The original anticipated wait time was 3-4 months, so I have been rather obsessively checking my email hoping to receive some type of news about the results or coverage. My fear is that we are losing months and months of time, under the assumption that the test is moving forward, when in fact is isn't.
We are also recently receiving piece-meal lab results ordered from a new biomedical doctor that saw Curren about 3 weeks ago. Some of the results indicate the possibility of specific abnormal metabolic conditions, which I of coarse googled and shouldn't have, as these specific abnormal metabolic conditions sometimes result in premature death. I know that the remainder of the outstanding lab results were reported to the doctor last Thursday (I called Quest) and so now I am rationalizing in my head the various reasons why the doctor hasn't given us the results yet. This, too, is adding to my anxiety.
And back in July, we had two EEG tests performed, both with abnormal results. Unfortunately Nemours did not give me much information about the results or what they might mean, so I have turned to Dr Google after requesting the written copies of the reports, which describes potential epileptogenic activity, possibility of underlying structural or metabolic abnormality, suggested lowered seizure threshold in left occipital, field spreading into right occipital and left posterior temporal area, careful clinical correlation is recommended, etc. I was hoping last week to gain more insight as to what these reports may mean at our routine follow up with one of Curren's Neourologists who's niche is epilepsy ("Epilepsy Center" is in the practice's name), but unfortunately he didn't offer anything remotely helpful. I have been anxious about what this doctor may say about the EEG reports for weeks now, and him providing no insight has added to my anxiety.
After getting nowhere with the local Neurologist, I called Nemours to schedule another appointment with Neurology so I can talk directly to the doctors who analyzed the EEGs and discuss the things in the reports that were never conveyed to me. It has been 5 days now since I left my message to request an appointment (at which point they reminded me that we weren't due for another appointment until January) and I have nothing. I emailed them asking to expedite the schedule request due to my concerns about my son's recent regressions and I have nothing. This is adding to my anxiety.
As we start to hone in on possible causes of my son's difficulties, I wonder if we really should be pushing so hard for these answers. What if it's not something I want to hear? What if this journey consumes me and I lose sight of the present? I wouldn't be able to live with myself if there were interventions that could make a difference and I didn't push hard enough to find them, but what if the road to get there honestly compromises our quality of life?
My current experience is applicable to all parents, and all life situations. Don't let your fear of the unknown rob you of your joy of the present. Enjoy each beautiful moment of life that you are blessed with, and savor those moments. Soak your babies up and don't let your fears shadow their triumphs.
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I am a mother, architect, wife, and a lover (not a fighter) - with a thirst for knowledge. My journey been recently refocused, as my family navigates through the world of medical and developmental uncertainty in hopes of providing every opportunity for my son to be his personal best in life.