Our family was honored to be invited as special guests to the Creighton Farms Invitational Golf Tournament in August 2019. Barbara Nicklaus, the wife of golf great Jack Nicklaus spoke about the Genomics Program at Nicklaus Children’s in Miami, which is technology that truly changes lives. We know because it changed ours dramatically.

Lilly is the sixth child of seven. Since birth, Lilly has been the sweetest, happiest baby. However, over time, she remained a baby. She didn’t hit her milestones physically or developmentally. We sought help from our pediatrician and specialists, we had a couple different types of genetic testing, but it gave us no insight into what was going on in our precious little girl.

As parents, we have a pretty big job. It’s our duty to nourish, nurture, instruct, love, and care for our children as they grow. We feel deeply responsible for these little ones entrusted to our care and our greatest desire is for them to be healthy, happy, and loved. As many of you know, when your child isn’t growing and developing, you start to panic because you know that could be a sign, a symptom of a bigger problem that could adversely affect their future. You start to seek answers from experts, from doctors, counselors, other parents, google every symptom. And when you don’t find anything that matches your situation it gets really frustrating. When a genetic counselor shakes her head and calls your child a “head scratcher”, your heart drops. There are days when you feel helpless, hopeless, and believe no one is ever going to figure out what is wrong with your precious child.

Then, the next day you get up and you start again. Because as a parent, you never give up on your child. You never stop advocating and working towards finding the right answers to give them the best life you can.

That’s where Nicklaus Children’s came into our story. Through their collaboration with RADY San Diego, they were able to give us the answers we couldn’t find anywhere else via whole genome sequencing. The relief of having a diagnosis of KAT6A, of seeing that list of characteristics that read like a checklist of Lilly’s symptoms is not easily described.

Still, once the relief of having the answers wanes, there are other emotions. There’s fear, sadness, and grieving. However, the information is invaluable as it has given us new avenues to seek assistance that weren’t open to us without a diagnosis.

Because of our involvement with The Nicklaus Children’s Health Care Foundation, Lilly was featured on the cover of their 2019/2020 issue of Fore the Children. We are honored that she was chosen to represent the thousands of children that the Foundation helps.

We are also privileged to be included as a part of the KAT6A Foundation, a group that works together, shares experiences and treatments, and truly cares about each and every person effected by KAT6A. Every milestone, every accomplishment, every discovery is celebrated not just by the individual, but by the group. And that’s what makes us all family.

Written by Christy

Bruno’s journey began in 2019. From his birth on October 11th, 2017 we already knew that something was happening but we didn’t have a final diagnosis until February 21st, 2019.

Even though the pregnancy was normal, when I was 37 weeks pregnant Bruno hadn’t turned yet. He was going to be born breech and my gynecologist convinced me to let them turn him around in my uterus to avoid a C-section. I agreed and when I was 40 weeks pregnant my labor was induced since Bruno’s heart wasn’t beating as well as doctors had hoped.

My labor was amazing and in only four hours I had my baby in my arms. I still cry when I think about that tiny beautiful face.

From there on things began to happen. Forty eight hours later we left the hospital without being able to get Bruno to breastfeed or take a bottle. He was fed 10 ml of formula with a syringe, and was diagnosed with hypotony cervical-axial and micrognathia.

From that moment on, everything has been agonizing. At only fifteen weeks he had a stomach protector and they changed his formula to a special milk without proteins from cow’s milk. It turned out he was lactose intolerant and he had almost got intestinal ulcers. Because of all of his stomach problems he wasn’t even gaining 50gr and we weren’t able to stabilize his weight in any way.

He spent every night crying and we cried with him. When we were able to correct his dose of medication from his stomach he started gaining weight. However, he was already 4 months behind in growth and we began to notice that he wasn’t doing many things that corresponded to his age as far as psychomotor movements. All of this, combined with an atrial septal defect ​in one of his many check-ups, sounded the alarm when he was only 6 months old. He already had a heart diagnosis, an appointment with the geneticist, check-ups with infant digestive specialists, and he had started with physical therapy and child psychology.

It all continued to develop and the operations started to become the new normal; heart surgery, tear duct opening, a possible knot if his esophagus. It was a nightmare that never ended and every time we went to the pediatrician it was something new.

Finally we received the feared but long awaited diagnosis; KAT6A syndrome. Although we thought that a diagnosis would give us encouragement, it was the total opposite. It erased all the hopes that we had that one day Bruno would lead a normal life. We forgot about all of the strides that he had made in the last 16 months and we thought that we would never be happy again.

At first the doctors only had bad news for us, saying that he would never be able to speak or walk because he had a severe handicap. However, little by little we have seen that with therapy and effort, great things can be achieved and we began to see the light again.

Bruno is currently going to physical therapy, a psychologist, speech therapy, and special therapeutic classes at the swimming pool and at the equestrian center with horses. He can walk and although he doesn’t speak he can make sounds and pronounce some syllables. He communicates in his own way despite his disabilities and above all, and most importantly, he is HAPPY.

On our journey we found the KAT6A Foundation on Facebook and through this group we have connected with other families in Spain. We also found the ‘Asociación KAT6A y Amigos’ which has helped us immeasurably to overcome every obstacle and has guided us to help Bruno progress as much as possible.

Thank you to all of you and to our medical team who have made something which once seemed so complicated, much easier for us now.

By Veronica

Spanish Translation:

Bruno comenzó su viaje en 2019. Desde su nacimiento el 11-10-2017, nosotros ya sabíamos que algo ocurría, pero no tuvimos un diagnóstico definitivo hasta el 21-02-2019.

Aunque el embarazo fue normal, cuando estaba de 37 semanas Bruno no se había dado la vuelta, venía de nalgas y mi ginecóloga me convenció para que les dejase darle la vuelta en el útero y evitar la cesárea. Me presté a ello y cuando cumplí las cuarenta semanas me provocaron el parto porque el corazón de Bruno no latía todo lo bien que ellos querían.

Tuve un parto buenísimo y en apenas cuatro horas tenía a mi pequeño en brazos. Aquella preciosa carita, aún se me saltan las lágrimas al pensarlo.

Y ahí empezó todo, 48 horas después salimos del hospital sin conseguir que bruno succionara el pecho ni el biberón, alimentándose de 10 ml desde una jeringuilla, y con un diagnóstico de hipotonía cérvico-axial y micrognatia.

A partir de ese momento ya todo fue un calvario, con apenas 15 días ya tomaba protector estomacal y le cambiaron a la leche especial sin proteína de leche de vaca porque era intolerante y casi había llegado a colitis ulcerosa. Debido a todos los problemas estomacales que tenía no cogía ni 50 gr con lo que no conseguíamos estabilizarlo de ninguna manera.

Se pasaba las noches llorando y nosotros llorando con él. Cuando conseguimos dar con la dosis de medicación adecuada para el estómago, empezó a ganar peso, pero ya llevaba 4 meses de retraso y empezamos a notar que había muchas cosas que por edad le correspondía hacer a nivel psicomotor y no las hacía. Eso unido a que el pediatra descubrió una CIA en una de sus múltiples revisiones, hizo que saltasen todas las alarmas y con sólo 6 meses ya tenía un diagnóstico cardiaco, una cita con genética, un control por digestivo infantil y había empezado en atención temprana con fisioterapeuta y psicólogo.

Todo siguió avanzando y las operaciones empezaron a sonar en nuestra cabeza, corazón, apertura del lacrimal, testículo en resorte, posible nudo esofágico; parecía una pesadilla que no acaba nunca, cada vez que íbamos al pediatra era una cosa nueva

Y llegó el temido pero a la vez esperado diagnóstico, Mutación en KAT6A, y aunque pensamos que un diagnóstico nos daría aliento, todo lo contrario, mató todas las esperanzas que teníamos de que algún día Bruno pudiera llevar una vida normal. Todos los avances que había hecho en los 16 meses que tenía se nos olvidaron, y pensamos que nunca más volveríamos a ser felices.

Al principio nos lo pusieron todo muy mal diciéndonos que no podría hablar que tenía una discapacidad muy grande y que no sabían si llegaría tampoco a caminar, pero poco a poco vimos que con terapias y con esfuerzo se podían conseguir grandes cosas y empezamos de nuevo a ver la luz.

Hoy por hoy, Bruno acude a fisioterapeuta, psicólogo, logopeda, terapia acuática y terapia ecuestre, ya camina sólo y, no habla, pero emite sonidos y dice alguna sílaba. Se relaciona y comunica a su manera a pesar de su discapacidad y, sobre todo, lo más importante, es FELIZ.

Por el camino nos encontramos con la Kat6A Fundation en Facebook y, a través de ellos, con el resto de familias que hay en España y con la Asociacion Kat6A y Amigos, que nos han ayudado lo indecible a

superar cada obstáculo, y nos han guiado para poder ayudar a que Bruno avance todo lo que sea posible.

Gracias a todos ellos y al equipo médico por hacernos fácil lo que al principio nos pareció tan complicado.

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I was born in 1989. The birth lasted for 33 hours. I was measured to be 49 cm and 3160 grams. During birth I had swallowed amniotic fluid. I could not breathe, and my skin turned blue. The doctors took me to the next room to pump. I also had a hidden cleft palate, so I had difficulties at breastfeeding. I probably couldn’t close my lips around the nipple, so I had to get fed with baby formula. From when I was 7.5 months to when I was 10 months, I was very cold with fever up to 40 celsius. I could often cry until I turned blue and lost my breath, so the doctors diagnosed it asthma. When I was three months old, I was hospitalized for 3 weeks with left foot in a knit because of an bone cyst.(which made it so that the foot broke). I had common cold, chickenpox and otitis, so I had 10 penicillin treatments through 6 months in my early years.

In kindergarten I was a silent and calm child. I remember the other kids didn’t let me in on their play, and I, instead of using words, reacted violently. In primary school, fifth grade, PPT (the school psychiatric team) gave me an IQ test, where my score was a little over “mentally deficient”. The doctor recommended to keep it, and put the term “mild” in front of it, as it would improve my right to facilitation at school. I was granted a classroom assistant, was placed front row in the classroom, window-side. Thus, I had to turn around to see what my classmates were up to. Socially, this was a disaster. I went to a speech therapist, and measurement of hearing. I have had a lot of otitis throughout my childhood. I had many infections as a child, but it’s rare that I become sick when I was in my 20’s. I took the most of it with a smile.

My adulthood has been kind of better. I have some struggles, because I got detected with ADD/ADHD Inattentive type back in 2014 during the autumn, so I’m struggling with some of the symptoms that comes with it as well. I got driver license in 2011, and I love to drive. I would like to expand my social life, but since I’m a calm and silent person(at times) I think it’s a little difficult to get to know more people, specially in occasions where there are many people. I can then seem shy or that I’m not interested, but I easily get distracted when there are alot of people around.

Now that I am an adult, I work in a protected company which is a permanently adapted job for people who for various reasons can’t be in ordinary work. I have great colleagues and it’s a great place to work. We are also good at taking care of health, environment and safety requirements I have two friends that I work with and since they don’t have a driver license, I pick them up in the morning and bring them to work. We use to meet after work and on weekends.

I’m happy that I found and can be a part of the KAT6A support group.

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18 years and 31 days after he took his first labored breath, we have a diagnosis for my boy.

The genetics department called a couple of days after Christmas to share the news, and I have been reeling since. For 30 days now, I have been down the rabbit hole of investigating KAT6A Syndrome. I waited 16 years for this news. And now that I have it, I’m a mixed mess of emotion. Relieved to finally have an answer. Shocked to finally have an answer, when I was resigned to not ever having one. I’m overwhelmed by the news and the information I’ve been devouring. Gratified to see that I have been providing Braeden with the best options for addressing the symptoms and pieces of this syndrome, with the exception of a supplement cocktail that may help.

I joined a Facebook support group that is nothing short of amazing. For the first time in Braeden’s 18 years and 31 days of life, I am reading story after story about fellow KAT6A parents and children and with tears in my eyes exclaiming “us too!” The camaraderie is uplifting and so much more helpful than I can adequately express. I’m seeing photos of kiddos that could be Braeden at that same age. That hold their hands in the same unique position that he does. There are only 180 or so diagnosed cases of KAT6A Syndrome, worldwide. In a month, that number jumped up from 166 known cases. Braeden is one of the older diagnosed patients. Most of the parents in the support group have younger children. Braeden appears to have a *middle of the road* case. This syndrome affects everyone differently. The severity of symptoms ranges from very profound disabilities, to very mild. I’ve said over and over that I’m an open book because I don’t want other special needs parents to feel the pain of isolation. So far, Everything that Braeden has dealt with, appears to be KAT6A related. The ACM1, apraxia, orchiopexy repair, sensory issues, failure to thrive, low muscle tone, acid reflux…….all of it. KAT6A Syndrome. Within this support group I’ve been able to give parents of younger patients hope that their kids will outgrow some of the symptoms they are dealing with now. I’d forgotten several things Braeden outgrew. Ankle braces, acid reflux, severe feeding difficulties among a few. From parents of the few patients who are older than Braeden, I’ve gotten similar comfort. The main thing being that this doesn’t appear to be degenerative.

The slightly unnerving part of that, is that we don’t know for certain. This Syndrome was only discovered a few short years ago. 2015, I believe.

I’ve chirped about this on Facebook incessantly over the last month. Today I needed to write about it here, to unburden myself of how overwhelmed I am. There are so many moving parts to Braeden turning 18, and this diagnosis is so profound right in the middle of all of those things….today I’m feeling the weight of it all. Today I’m exhausted. And hell, for shits and giggles, my body decided to throw another health crisis for me into the mix. Hello kidney stones, my old nemesis. I passed one during Braeden’s birthday week, and there are 4 more waiting in the wings. Today I have low back pain again, and I am in a cold sweat that another meteor is ready to bust loose.

Today the weight of all of it is heavy.

Today I’m allowing myself some tears, some escape TV watching, and grace for not accomplishing anything on my to-do list.

Tomorrow, I will fill out the research questionnaire online, and register Braeden so that his medical history can be used to further the medical community’s knowledge about KAT6A Syndrome.

Next month, I was gifted airline tickets so I can attend the second annual KAT6A clinic. I’m so looking forward to meeting other people with this syndrome, and their parents who truly understand what this life is like. I think it will be very emotional and uplifting. I’m excited to learn more from the researchers and doctors who are working hard to learn more about it.

For the rest of today…..grace. Giving Braeden a bath. Reading to him for awhile before bed time. Packing his bag to take him to work with me tomorrow. Tonight I will read something that isn’t geared toward finishing the guardianship process, or healing my kidney stones and thyroid and skin cancer. Tonight I will spray my pillow with lavender, and meditate. Tonight I will turn off my brain and sleep. Tonight I will be *brave* enough to *believe* that things are always working out for us.

by Sonia

Read more from Sonia at her personal blog https://andhecallsmemommomm.wordpress.com/

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It feels funny even writing this title, Special Needs Child, what does that mean? All children are special and have different needs. It might be easier to use the other “label” we have recently received medically fragile/technology dependent to describe my son, Toby.

Growing up in a small urban community of 30,000 during the 70’s and 80’s, you knew most people and while there were some kids that needed a little extra, there weren’t many. Unfortunately it wasn’t till I got married and started coaching swimming with Special Olympics that I became involved with the disabled/handicapped community. Over the 15 years that I spent with the team I learned a lot and made some great friends (some of whom now call my son their friend as well) but I will get into that latter.

Zachary my older son was born healthy and only spent the minimum time in hospital. Even to this day he is overall healthy and has developed normally hitting the developmental milestones by which the doctors measure a child. Almost 2 years later my son Toby was born. This was a very different experience.

Toby was born 8 days early on a Friday the 13th. I had to travel for business and was flying home when the doctors delivered him by emergency c-section. My wife had labored part of the night and my parents had come down to take her to the hospital and look after Zachary. When my wife arrived at the hospital she was already dilated but her water hadn’t broken. The doctors discovered that Toby was sideways and tried to turn him before delivery. The doctors discovered that Toby was in distress so decided to do a c-section with epidural. After they broke her water, the doctor’s lost Toby’s heartbeat and decided that they needed to do an emergency c-section with a general anesthesia. When delivered, Toby was without vital signs and had to be resuscitated. The pediatrician was on the phone with the doctors who did the delivery rushing to the hospital in his car so the anesthesiologist and the delivery room nurse resuscitated him. As the doctors weren’t sure how long he was without vital signs and he was having difficulty breathing, they put him on oxygen and rushed him into the special care nursery.

When I landed at the hospital, I called home expecting my wife to be there only to be told that my mother had taken her to the hospital a few hours before. I then called the hospital and spoke to one of the nurses who had just come on shift. All she would tell me on the phone was that it was a boy and he had been delivered by c-section and I should try to get to the hospital as soon as possible. When I arrived at the hospital, I headed right to the maternity ward expecting to find my wife, my mom and my son there. I was told that my son was in the nursery and I could see him but my wife was still recovering from the c-section. I visited with Toby for a few minutes and then went to see my wife who was just coming out of anesthesia. It was different seeing him, all hooked up to various monitors and on oxygen to help him breath. Later that day the doctors came to see us and discuss some of what had gone on during the delivery and they continued to monitor him in the nursery. My wife wasn’t able to get into see him till later the next day as they didn’t want her tearing the stitches. I made sure that Zachary came in to see his mom and new little brother.

Over the next few days, the doctors continued to monitor him and run various tests including head ultrasounds, CT scans, x-rays and bloodwork. Most times the nurses were really good and would let us know when the tests results were received, but the CT results seemed to take forever to be received. Eventually they said that the doctor was coming up to discuss with us. Shortly before the meeting, an unknown individual showed up in the nursery. She spoke with the nurses in hushed tones and this is when I started to suspect that something might be seriously wrong. The doctor arrived and as there were other parents in the nursery asked us if we would like to step across the hall to discuss the results. As we were leaving the nursery, the unknown woman followed and picked up a box of Kleenex on the way out the door. At this point, I knew we were starting a difficult journey. The doctor and social worker discussed the test results. They showed that Toby wasn’t developing as expected. They indicated that they could do further testing here at this hospital but would have to send the results to a children’s hospital about 15 mins away to have them interpreted or they could see about transferring him to the children’s hospital where all the testing could be done and we would have all the pediatric specialists we might need at our finger tips. This was day 5 after delivery. They suggested that we go home that evening (first time my wife had slept away from the hospital since Toby was delivered) and let them know in the morning.

The next morning we went back and met with the doctors. We felt that it was best to transfer Toby to the children’s hospital and so our 5 week journey there began. During his time there, more tests were done, specialists consulted and he continued to monitor for what the doctors called “failure to thrive”. During this time, my wife lived at the hospital and I tried to work, manage home and spend time with Toby. Zachary got to spend quality time with both sets of grandparents and also got to see his brother. Everyone said that he was continuing to grow but not at the rate which they hoped/expected him too. After a total of about 6 weeks in hospital we were finally able to bring him home. His first official trip out was to attend my swim team’s annual pool party and BBQ. The second was to visit with his great-great Auntie who was visiting from the east coast. Over the next year, he continued to be followed by multiple specialists and at a developmental pediatrician. There were a few minor medical issues which were dealt which including club feet surgery (Tendon transfer bilaterally) at 18 months old and strabismus in both eyes at ?. We were told that genetically there was nothing found on the tests done and that they believed the developmental delays he was experiencing were a result of his traumatic birth.

Toby struggled when he started in school because he didn’t speak. We were able to get him additional resources but the education system was recommending that we put him into a communication program which would help him develop functional communication. At age 6 we did this thinking that this would help him and still believed that it was in his best interests to help him grow and develop into the person he was and be able to communicate with those around him. After 3 years in this program, he was making little progress and we were becoming frustrated with some of the “professionals” who were supposed to be working with him. He had not progressed to using assistive communication devices such as his Ipad to communicate and instead preferred to try to verbalize and attempt to speak. At this point while he was able to function at home he was so far behind his peers at school academically that he wasn’t going to be able to return to a regular classroom and we made the decision to integrate him into a lifeskills class. We met with the teachers, school board professionals and made this difficult decision. Since entering this class he has begun to flourish and began to speak more because he was now with classmates who while they all had limitations, most of them did speak and he picked up on this and did start speaking more and his speech began to improve. This improvement continues till today and he is now able to make himself understood verbally in most situations. We see that while his expressive language continues to lag behind, he does understand (receptive language) is much better. We aren’t sure how much of his surroundings he actually understands but it does appear more than he is able to tell us in words.

About 2 ½ years ago we had a number of bouts of pneumonia and our new journey began. Initially they couldn’t understand why he would get so sick from the pneumonia and eventually determined that he had an immunodeficiency. They began treating this and we noticed some improvement. The doctors at our local children’s hospital tried to do a pulmonary function test to determine what if any damage had been done by the recurrent bouts of pneumonia. Unfortunately he wasn’t able to perform the testing at their location due to equipment issues so he was referred to another specialist at a nearby children’s hospital who gathered information, looked at his chest x-rays, did some further testing and came back to us with the question “Is the PFT really the most important thing here or do we need to find out what is going on and work from there?” We agreed that it was more important to determine underlying cause of the lung issues. We went in for what we thought was a bronchoscopy and CT of his lungs to see if they could identify the cause of what they were seeing in the chest x-rays of his lungs. After reviewing the CT the doctors indicated that he appeared sicker than they had expected and admitted him and wanted to run further testing. Over the next 2 weeks he underwent a double bone marrow biopsy, lymph node biopsy and lung resection as well as the bronchoscopy and bronchial lavage (washing of the lungs). All of these came back inconclusive or not clear. No bacteria or viruses grew in the material from his lungs and there wasn’t any evidence of malignancy so they continued to test and coordinate with multiple specialist. After a month as an inpatient they said, that they didn’t know exactly what was going on but we could take him, they would continue to follow him and sent us home with oxygen to used at night and a high dose of prednisone which they hoped would help clear up his lungs, shrink his spleen which was enlarged and hope to see an overall improvement in his health. They also did some genetic testing as they indicated it had come a long way in the years since had testing done at birth.

Months later the results of his genetic testing came back. It showed that he had a “de novo” genetic mutation. It was called KAT6A and had only been identified in the last 3-5 years. No one seemed to know much about, there was not currently any curative treatment and all they could offer was to treat the symptoms caused by it. Through doing research and getting to know others with this rare genetic diagnosis we have discovered that some of the issues he has had at birth are likely related to this misspelling of his genetic makeup but it doesn’t explain his immunological issues. He continues to be treated regularly for the immunology issues and overall his health has improved. He is getting sick less and we are seeing gradual improvement.

At this time, Toby is the oldest of 8 youth in Canada who have been identified and one of approximately 170 in the world, who have this variation in his KAT6A gene. This is still a very rare condition and while we believe that there are likely more people with variant it is a costly and lengthy process to undergo the whole genome sequencing required to identify it.

While it has had its challenges over the years, I wouldn’t trade the experiences and people we have meet over the years for anything. Toby is a happy, loving young man who is growing up and takes his challenges in stride. When he meets a new doctor and they ask if they can poke or prod him to see what an enlarged spleen feels like or listen to his chest, he is more than willing. Just because the doctors say your child is unique or a conundrum, don’t look at this negatively and think maybe by learning about my child they can help someone else.

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Christmas has always been a big deal in our house. All of us, kids and parents, enjoy the feeling of Christmas. We especially love the glittery, sparkly decorations that come along with it. We always have lots of garland, lights, and decorations in our house—you know—all the sparkly fun things kids love!

When you have a special needs child, those things can be either wonderful or horrific. For Holden, who is three and a half years old, it depends on his mood of the day. This year, when we pulled the Christmas tree out of the bag for the first time, we thought poor Holden was going to have a heart attack! A big, green, prickly, scary thing in the house! Holden must have thought it was a big green monster. But we got it set up with all the decorations and lights and he began to be curious about it. Pretty soon he was pulling ornaments off the tree. As the mom of three boys, I will be the first to tell you that the last thing you want is a child pulling ornaments and decorations off your beautiful tree. But when Holden began to do that instead of showing fear or aggravation I was happy! We were all relieved he was no longer scared of the tree and was enjoying having it in the house. We let him explore and figure out that the Christmas tree was harmless and was not going to hurt him.

Like many kids with special needs, Holden does not do well with change, and he has become much more observant of his surroundings over the last year. So many different things can upset him and cause him to be very unhappy. Now that it is the Christmas season, our house is not looking the same as it always does. The first few days with the decorations, he was really confused and upset about the changes. With a lot of patience and some time, Holden has become used to all the new things in the house and is actually starting to enjoy some of them.

Since we never know what simple thing might be the one thing that he just doesn’t agree with, we were worried about what his reaction to Sant Claus would be. Surprisingly, Holden was perfectly fine seeing Santa and sitting on his lap! His older brothers were sitting next to him, so that made him feel safe and secure.

We hope everyone has a blessed Christmas season.

Love,

The Green Family

It has been an exciting few months in our household. We welcomed our daughter, Emma, on July1st, 2018. Jack has been a wonderful big brother thus far. He is beginning to notice Emma more and more each day; there are even times when he seems annoyed by his little sister (as a typical three-year-old might)!

Even though life has been quite hectic since our newest addition arrived, we have made sure to continue with all of Jack’s weekly therapies. One therapy in particular that has made an impact is Aquatic Therapy. Jack works with a PT in the water one on one every Wednesday morning for 45 minutes. Not only does Jack truly enjoy swimming, but the benefits are clearly evident. Each session provides Jack with the opportunity to improve core strength, mobility, balance reactions and range of motion. He is happy and motivated to move in the water. The therapeutic properties of the water allow Jack to move more freely and independently. He tolerates handling, stretching, and active exercises, in conjunction with lots of sensory input. Jack often smiles throughout his sessions and happily kicks and splashes his way around the pool. It goes without saying that physical therapy is so important for our KAT6A kids, but we can honestly say that Jack would not be making all the progress that he is without his weekly time in the water!

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Hello everyone,

I got naturally pregnant in 2013. During pregnancy, the diagnosis of hydronephrosis in two kidneys was reported in the 23rd week at the baby and then issue was followed by doctors.

A caesarean operation was performed at the 38th week due to a decrease in the water in the uterus and an increase in hydronephrosis in the infant’s kidneys.

On February 18 . 2014, Our little boy Rüzgar was born. When we saw him the first time , The doctors told us that Rüzgar was trapped in my abdomen and that he had an uncut testis.

Rüzgar was circumcised with the diagnosis of hydronephrosis in the first week after his birth. Circumcision regulated the left kidney function of Rüzgar and a month later , it was decided by the doctors to undergo surgery for left inguinal hernia.

When Rüzgar was three months old, we noticed that he did not make any eye contact with us and did not follow us. We decided to go to a doctor about this. The doctor said this was not a big problem and they would follow this issue. They also advised us let Rüzgar to watch the cartoons on the television. Doing this, still did not make any progress but we followed the instructions.

In all these processes, Rüzgar was fed with my breast milk. As his sucking reflex was not so good, we fed him my milk with glassess.

When Rüzgar was six months old, he had epileptic seizures. After the result of EEG, we started to use a drug called Sabril and the result of the brain MR was clean. The EEG results in later processes were clean. In the meantime, a serious problem of constipation did not leave us. He was fed with breast milk for approximately 7 months.

During this process, the kidneys were examined frequently . The functions of the left kidney were stabilized but the doctors decided to operate for the right kidney . Hydronephrosis was rapidly enlarged, and kidney stones were made, and the stone pain began to be serious.

On the other hand, Rüzgar started physiotherapy training and an intensive training was going on. We changed the drug Sabril with Convulex syrup for Rüzgar ‘s epilepsy seizures ,because of the serious side effects for eyes . We are still using Convulex Syrup as 75 cc in the evenings – 75 cc in the mornings.

Our neurologist thought that different medicines would be good for Rüzgar . For this reason , we used three curing Cortexin needles. Later, we used following drug, which is used by homeopaths in the name Cerebrum, for three months. In fact, we tried a diet called GAPS, but we decided that it was not suitable for us because of the kidneys. But I think this diet was good.

In the meantime, a diagnosis could not be found, Doctors told us that he was more close to autism.

When Rüzgar was three years old , we went to the genetic doctor. We did some test given by the doctors , but due to lack of technology in Turkey in that time , the prognosis could not be make . The doctors also informed us that the heart of Rüzgar should be checked. We quickly went to a doctor about the heart and learned that there was a hole in the heart that was not serious, but which had to be followed up. This process is still followed up by doctors.

In addition, we have started physical therapy, pool therapies, sensory integration training, and physical therapy using the Anat Baniel Method. With the help of these lessons / trainings, Rüzgar began to sit and crawl. Those days he didn’t make a lot of noise, now he’s turned into a kid who always shouts and tries to make sounds. Now he is standing on his own by the window and started to walk side by side. He still can’t stand up alone, but he can stand up, with support.

Controls of the kidneys is still continuing . In addition, we are in constantly checked because the kidney is still an issue .Besides all this he drools alot, we call it honey mouth

We went to a doctor in Uster city in Switzerland, which is recommended to us about eye focus. He gave us some lights and sounds. Rüzgar can be a good musician in the future , he has a good ear for music and rhythm.

He is the happiest and the most peaceful child of the world When i look at him i thank God for the moments i spent with him . Everyone’s story is different, I know every child is special, but when you look at Rüzgar, especially when your eyes meets his eyes , you will get overfloated with
magic .

Unfortunately we have no idea how to reach him and how to get in his world.

I hope you can be a light and hope for Rüzgar and us.

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Important Safety Tips You Must Teach Your Child if Lost

IIt’s a parent’s worst nightmare and can happen so quickly. You are in a public place and your little one is right next to you, but you look away for one second, and he is gone.

Why teach young kids what to do if they get lost?
Because it can happen to the best of us. I arrogantly used to think that good parents like myself don’t lose track of their children. My two older boys (10 years apart in age) had never gotten lost or separated from me on an outing. But then the twins came along. And humbled me to my core!

The twins have always found great pleasure in going in opposite directions and wreaking havoc at home. So taking them out by myself when they were smaller required keeping them contained in the double stroller. They didn’t like being confined, but it was necessary to prevent one from getting lost or separated from me.

But one day, I foolishly attempted to take them both into the store without the stroller. I only needed one thing, how hard could it be? One toddler on each side of me holding my hand. Easy enough. Until I had to release a kid’s hand so I could pay. One twin took off and when I let go of the other to catch the run-away, he thought it was all really funny, so he darted off too! I somehow grabbed them both, restrained one kid between my knees and the other with one hand while I clumsily used my free hand to finish paying.

PRO TIP:
To make my life easier, I shop for EVERYTHING possible online and use grocery store pickup services and pharmacy drive throughs. I go to great lengths to NOT take the twins out by myself! While it seems the simple solution is to minimize our outings, the reality is that I needed to start teaching the twins what to do if they became separated from me or got lost. And obviously I needed to teach the little turkeys to obey and not run from mommy….but that’s a whole ‘nother blog post!

What if your child is non verbal?
One of the twin boys, Beckem,was born with an extremely rare disorder called KAT6A. One of his struggles is that he is non verbal, yet he comprehends everything that is being said to him. Although he lacks the motor planning to speak with his voice, he communicates with us quite well with some sign language, some word approximations, and gestures, but a stranger wouldn’t be able to understand. Beckem also does well with his AAC device, but he’s still too young to be expected to keep up with it. Before we went to Disney, I brainstormed and researched for months for ways to keep track of the twins in case one got separated from us. At 5 years of age, I knew that Adler would be able to articulate to a grown up the information needed to reconnect with us, but there was no way Beckem would be able to. I looked at those kid gps gadgets but that just didn’t seem practical for us. There are also temporary tattoos you can personalize with your info, but Beckem’s skin is so sensitive that I wasn’t sure if that would work. The identification bracelets seem to be a nifty solution, but Beckem refused to leave his bracelet on when we went to the water park last summer, so I knew that wouldn’t be an effective option.

After all of that searching, I finally thought of the perfect solution and it cost less than $5!

A pet ID tag!

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I decided I would attach the tag to Beckem’s shoe.  I ordered several of the yellow star tags so I could place one on different shoes he might wear and also put one on his backpack that he carried in the airport.  I also put tags on Adler’s shoes since he hasn’t memorized our phone numbers yet.  However, even if he had learned our number, if Adler were separated from us, he would likely be so upset that he wouldn’t be able to recall it.  The tag has a little key ring and I simply attached that the the shoe string of his tennis shoe.  For his Crocs, I used a piece of yarn and tied it through the holes in the shoe.  To secure the ID tag to his boots, I use a twist tie.

So that’s it…put a dog tag on my kid? I wish it were that easy! But, you will also need to teach and prepare your kids for what they should do if they get lost.

What parents can do
There are several things parents need to do to prepare for the possibility of this situation.

Let’s Talk
First, you want to talk to your children about the importance of NOT wandering off from you, and what they should do if it does happen. Don’t make it a scary conversation and reassure them that they WILL be reunited with you.

What to Teach
Now, you want to explain to your kids that if they become lost, you will be looking for them and teach them to stay put. If they are also frantically running around or standing in a corner crying, it will take longer for you to find them.

Have them practice what standing tall and still looks like.

Say my name
Teach your child that he should stay put and shout for mom or dad as loudly as possible over and over.

Beckem does say “mama” and “da-da”, but his voice is very quiet. We practice at home periodically how to say “mama!!” loudly, and he thinks it’s great fun! You also should teach your kids their own first and last name asap and mom and dad’s first and last name as soon as they are old enough so you won’t be paged over the intercom as “mommy”. (I taught Beckem to spell and type his name as soon as he was able since he’s unable to verbalize it.)

It’s also a good idea to have kids memorize your phone number, although, I’m not going to rely on their ability to recall it if they are lost and terrified.

If yelling doesn’t work…
I’ve taught my kids to look for a mommy. Chances are, a mom has already intervened though, since every mom within earshot instinctively reacts when hearing a small child yelling “MOMMY!!!!!!” I’ve instructed Adler to find a mommy and speak big and clearly saying: “My name is Adler and I’m lost. Can you help me call my mommy? Here is her phone number on my shoe.” We’ve taught Beckem to find a mommy and say: “Mama!” and point to his tag on his shoe.

Some other things parents should do
Make sure you have a current photo of your child just in case. During our week at Disney, I took a photo of the boys with my cell phone each morning at the park entrance, in the event that I needed to know what they were wearing. I like to think I would remember what I dressed the kids in, but I know that if one of my boys wandered off, I would be so shaken that it would probably be a struggle to remember my own name!

Practice and review
Periodic reminders and practice can help our kids remember what to do if they become separated when in a public place. Being prepared can minimize a potentially scary situation and reunite parent and child quickly.

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Parents and caregivers of children or adults with KAT6 disorders are the first to recognize whether the person they care for is in distress.  Those continually looking after the person’s needs are the best ones to intervene and advocate for medical care when it appears that a problem is present and getting worse.  But what are we looking for and when might it call for emergency care?

INTESTINAL BLOCKAGE

Gastrointestinal issues are common with KAT6 disorders.  Low muscle tone throughout the body may mean low motility in the gut — weak contraction of the muscles that mix and propel contents in the gastrointestinal tract.  When there is a temporary lack of normal muscle contractions of the intestines this is known as ileus — not a blockage, but a stoppage.  (Think of a blockage as a train wreck, preventing any other train from passing through, and think of a stoppage as merely a train sitting on the tracks and failing to move along.)

When the contents of the upper or lower bowel cease to move, the resulting mass can become enlarged and can harden as it dries out, stretching the part of the intestine where the mass occurs.  Regular contractions can return and eventually move it along, but if the contents sit too long they can begin to ferment and decay, with potentially serious results.  Vomiting and diarrhea, for example, are normal consequences once the body applies its other resources to the obstruction.

If it does not eventually start moving on its own it may respond to non-invasive treatments such as stimulants taken orally or a rectal enema, depending on proper assessment of the location of the problem.  But if there is a physical barrier to continued movement of intestinal contents, the problem can quickly become life-threatening.

MALROTATION AND VOLVULUS

Around the tenth week of gestation, as the intestinal tract is developing, it normally moves from the base of the umbilical cord into the abdominal cavity.  As the intestine descends into the abdomen, it makes two rotations and settles into its normal position.  When a portion of the intestine, or even the entire intestinal tract, fails to lie properly in this space, it ls known as a malrotation.

A malrotation may cause immediate symptoms and problems after a baby is born or may lead only to intermittent trouble, or it may cause no problems at all.  In some people it is not discovered until well into adulthood or perhaps never discovered at all.  In others, it can be the source of repeated obstructions.  The point is, a malrotation is an anatomical defect and one that must be suspected if problems arise, especially in early childhood.  It can lead either to continuous or intermittent problems but is not necessarily dangerous.

When a loop of intestine and the membrane that holds it in place twist around each other like sausage links or a kinked garden hose, this causes a bowel obstruction called a volvulus.  A certain kind of volvulus in a horse is commonly called a torsion.  It is not going to clear and open back up on its own, and normal muscle contractions in the gut are not going to force a trapped mass of intestinal contents to move past it.

The trapped material, already partially digested, continues to break down, though, and some contents may be ejected as diarrhea or gas, while most of it will remain and swell the gut.  A person suffering a volvulus, who enters emergency surgery soon enough, may still lose part of the intestinal tract in surgery.  Without emergency surgery a volvulus is almost certain to be fatal.

If a volvulus is suspected in an emergency room, a buildup of gas in the intestine may show up on a series of x-rays, which must be taken at intervals long enough for changes to appear but no so long that surgery comes too late.

OTHER GI ISSUES

The esophageal sphincter is the valve between the esophagus and the stomach.  When the muscle that keeps this valve closed is weak, a blast of burning stomach acid may rise as far as the throat.  This is acid reflux.  A baby with KAT6A or KAT6B can be resting quietly in a baby seat, alert and cheerful, and suddenly scream in pain and terror.  If this happens with any frequency, reflux should be suspected when nothing else is likely.

Dumping syndrome is a group of symptoms, such as diarrhea, nausea, and feeling light-headed or tired after a meal, that are caused by rapid gastric emptying, a condition in which food moves too quickly from the stomach to the duodenum.  This can become an issue after a person has undergone GI surgery.  Adjustments in diet or medicine can resolve things, and, if surgery was involved, time may be the best healer.

OUR NEED TO REMAIN VIGILANT

Communication problems are common with the KAT6 population as well as an apparent high tolerance for pain.  Children and adults with KAT6 disorders, especially those who can’t tell us that something hurts or where it hurts, need to be monitored continually for lack of gut movement.  Constipation, (a general term for any disruption of intestinal activity that leads to pain and irregularity of bowel movements), can make a normally cheerful person irritable.

A volvulus is a rare occurrence in the general population, but among the KAT6 population it seems common enough to be of serious concern.  Although we are still studying the matter and don’t have statistics, it appears that untreated bowel obstructions are the leading cause of death among children affected by KAT6 disorders.

Many of those with KAT6 disorders are tube-fed through a gastrostomy.  For some, this is their only source of nutrition, and so variations in gastrointestinal activity are less likely to be caused by daily changes in diet.

What is the person’s normal frequency of bowel movements?  Has it been a day longer than normal?  Two days?  Is she also becoming irritable, combative, unable to sleep?  Does this happen in repeating cycles?  What does her blood work show?  What does a gastroenterologist say?  Do cycles of irritability correlate with cycles of unusual toilet contents?  Someone close to the patient needs to be asking these questions and insisting on answers.

People with KAT6 disorders may show no signs of a bowel obstruction until it has progressed to a serious degree.  They may quietly tolerate the increasing pain until it has become severe.  An obstruction can go from bad to dangerous quickly.  It is hard to differentiate an obstruction from other gastro-intestinal issues.  Obstructions can happen again and again and can strike at any age.

While it is probably more likely to become an issue early in a child’s life, an affected person who has a KAT6 disorder can seem to be OK for years, perhaps irritable at times for no apparent reason.  Just because it hasn’t been diagnosed at an early age it could be that a complete obstruction simply hasn’t happened yet.  The best prevention of complications is be on top of it all of the time.  Not all doctors understand that, with a bowel blockage, you can still pass diarrhea — the assumption seems to be that if they’re passing anything at all then there’s no obstruction.

Medical services vary from country to country, and while another country may have excellent hospitals and perfectly competent doctors, they may also have different approaches to parent involvement, different protocols for intervention, and different standards for what can and should be treated.

Compounding the danger, a doctor may not consider an intestinal obstruction if a parent or caregiver hasn’t suggested it, and so a doctor wants to ascribe a change in behavior to anxiety, a virus, a food allergy, and so on.  Meanwhile the child has mere hours to get the problem resolved or else irreversible damage has been done with a high potential for fatal results.

LIVING WITH IT

We aren’t supposed to tell people about our poop or ask others about theirs.  With KAT6 in a family we could save a life if we get beyond that taboo.  In our own experience, Beth and I share in all phases of the care of our son, Sam, who is now 32 years old.  He is one of the more severely disabled individuals with KAT6A syndrome, and so we must pay constant attention to all the signs he gives us.  We “read” his behavior, we both examine his bowel movements daily or at least describe to each other what he has done.  (He even has an “I POOPED TODAY” T-shirt.)

Sam has had a gastrostomy and feeding tube since he was a baby and receives all medicine and sustenance through the tube.  He had a nissen fundoplication during his first surgery as a baby, so he cannot burp or vomit.  He had a malrotation of the duodenum at birth (corrected by surgery), reflux as a baby, a volvulus before he was two (indicated by changes in a gas pocket on successive x-rays), a second near-fatal obstruction due to adhesions, and numerous instances of ileus and other partial obstructions requiring hospital stays.  As an adult he is now treated for ulcerative colitis.  He does not walk and can’t speak.  But he is engaging and even mischievous, affectionate, enthusiastic, and popular.  When he hurts, his only ways to show it are in withdrawal, resistance, and restlessness.

We are fortunate that Sam has had doctors who care about him as a person and who listen to us, his parents.  His doctors, though, need to trust what we are telling them, and so our information must be reliable.  By educating ourselves, paying close attention to the signs that Sam gives us, and making sure we communicate consistently and accurately with medical providers, we have been Sam’s best advocates.

Many parents have observed GI benefits from a mitochondrial cocktail and other supplements, such as Cytra-3. Learn more about these supplements by watching Dr. Richard Kelley’s presentation from our 2022 Conference. It is essential to consult your child’s physician before starting anything new.

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On March 24, 2022, The KAT6A Foundation hosted the second KAT6A and KAT6B Virtual Symposium.  The event was designed to solidify the KAT6A and KAT6B research network of clinicians and researchers through identification of research gaps, opportunities and collaborations. The symposium series aims to drive patient- centered and collaborative research to improve outcomes for individuals with KAT6A and KAT6B syndromes. The symposium series also aims to spark new collaborations among the KAT6A and KAT6B research groups and healthcare communities.The first KAT6A and KAT6B symposium, conducted in 2021, discussed a range of neurodevelopmental challenges faced by children with KAT6A and KAT6B gene variations. The second symposium expanded on the stakeholder representation to include parents of children with KAT6A and KAT6B gene variations along with health care professionals, clinicians, and researchers. This symposium focused on understanding the impact of KAT6A and KAT6B gene variations on speech and language development, a domain that is most commonly affected in this population of children.10 speakers and nearly 60 members of the KAT6 community attended the the symposium. The symposium ran for three hours and was organized in two sessions: the first session provided an overview of the KAT6A Foundation’s goal to empower patient-centered research and initiatives led by the Foundation to support research. The second session focused on understanding the pathophysiology of KAT6A and KAT6B related speech and language disorders.

Please read the symposium recap pdf for a complete summary of each presentation. The next virtual symposium is tentatively scheduled in September 2022. This symposium will focus on unraveling the range of gastrointestinal difficulties faced by individuals diagnosed with KAT6A and KAT6B syndromes.

The KAT6 Foundation is honored to receive a third year of funding from the Chan Zuckerberg Initiative (CZI), in the amount of US$150,000. The grant supports the expansion of the KAT6A/KAT6B Research Network and accelerates our work to find treatments or a cure for KAT6A and KAT6B syndromes.

“We are so grateful to the Chan Zuckerberg Initiative for their continued support of the KAT6 Foundation and the rare disease community. Their continued support recognizes the great progress our foundation has made in developing and organizing the community of researchers seeking to understand and treat KAT6A and KAT6B syndromes. We look forward to continuing to develop new research opportunities and collaborations as we seek future sustaining funding opportunities,” shared Jordan Muller, chairperson of the KAT6 Foundation.

In February 2020, The KAT6 Foundation was selected as one of thirty patient-led organizations for CZI’s Rare as One Project and was awarded a grant of US$450,000 to be used over 30 months. This grant has enabled the foundation to expand its Research Network by funding a science director, research coordinator, and patient registry coordinator, which helped facilitate the first KAT6A & KAT6B Virtual Symposium in 2021. This was the first collaborative research event organized by the KAT6 Foundation in which 16 speakers presented their research related to KAT6A or KAT6B genes. This conference provided researchers an opportunity to discuss their findings, ask questions and receive feedback while strengthening collaboration. In June 2022, these funds will allow us to host the 3^rd International KAT6A & KAT6B Conference so that we can bring families, researchers, and medical doctors together for the first time since 2019. Furthermore, the CZI grant has been critical in helping us improve fundraising and awareness initiatives by supporting marketing and communications costs.

As we move forward, we will continue CZI’s mentorship program, which has provided us with the valuable opportunity to collaborate and learn from other rare disease organizations. This additional funding will foster greater collaboration between all the researchers currently working or interested in KAT6 through subsequent meetings in the KAT6A and KAT6B Virtual Symposium series. The opportunity CZI has provided us to strengthen our Research Network has allowed us to be a driving force in international KAT6A and KAT6B research. It is an honor to serve the KAT6 patient community as we move forward in our mission to ensure equity in access to testing, knowledge, and therapies for KAT6 patients around the world. Thank you for your continued support.

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KAT6A Families,On March 1, 2018, Dr. Francis Collins, the Director of the National Institutes of Health (NIH) dedicated his blog posting to Dr. Valerie Arboleda’s research on KAT6A.  This blog post provides great visibility for our community and the KAT6A Foundation, and is a very good summary of her research plan. https://directorsblog.nih.gov/…/creative-minds-looking-fo…/…

I also wanted to recognize and thank all of the families who supported the Children’s National Race For Every Child over the past several years. It was funds you raised for those events that supported her initial research. This research provided the early findings that helped her win the NIH grant that will help sustain this research going forward. So congratulations to all of you for helping further KAT6A research. And thank you for your continued support of our new KAT6A Foundation as we continue to raise funds to support future research.

Jordan Muller

Chairperson of the KAT6A Foundation

On February 3, 2018, the first KAT6A clinic was held in Baltimore, Maryland, at the Kennedy Krieger Institute. Nineteen families attended and several more followed the clinic by livestream.

We were pleased to have in attendance and as speakers Jacqueline Harris, M.D., Ph.D., Pediatric Neurologist from the Kennedy Krieger Institute in Baltimore, Hans Thomas Bjornsson, M.D., Ph.D., Director of Epigenetic and Chromatin Clinic and Assistant Professor of Pediatrics at Johns Hopkins Hospital in Baltimore, Jill Fahrner, M.D., Ph.D., Assistant Residency Program Director at Johns Hopkins Genetic Medicine Residency Program and Assistant Professor of Pediatrics at Johns Hopkins Hospital in Baltimore, and Richard Kelley, M.D., Ph.D., former Director of Division of Metabolism at Kennedy Krieger Institute in Baltimore and current researcher at the Division of Genetics and Boston Children’s Hospital.

After a welcome by KAT6A Communications Director Brittany Green, Dr. Jacqueline Harris presented an overview of the KAT6A clinical syndrome. She explained that KAT6A is a histone modifier epigenetic disorder. This means that the gene function is changed, not the gene sequence, and it is influenced by the histone machinery. It is most often de novo, which means that the genetic change happens in the child and is not inherited from either parent. She reported that there are only a few documented cases, so not much is known about KAT6A syndrome. Researchers need more cases to study. However, there seem to be some features that are nearly universal and some features that seem to be related. Some of the universal features include hypotonia, feeding problems, congenital heart disease, eye or vision problems, skull abnormalities, distinctive facial features, and global developmental delay. Less common but probably associated features are small birth size, perinatal complications, seizures, specific behavioral features, sleep disturbances, immune system irregularities, dental abnormalities, hand abnormalities, and brain MRI abnormalities. She concluded by stating that current researchers learn most from the patients and their families and by drawing from information from other similar epigenetic syndromes.

Next, Dr. Kelley spoke about mitochondrial dysfunction in KAT6A. KAT6A affects metabolic protein absorption, and children with this disorder often have abnormal levels of certain plasma amino acids. Some that he mentioned were citrate, asparagine, and phenylalanine. Using common lab standards, amino acid levels often seem within normal range but a doctor who specializes in mitochondrial disorders uses a conversion scale to determine whether there is a mitochondrial disorder. Dr. Kelley has been working with several families to analyze plasma amino acid levels and then recommending parts or all of a mitochondrial cocktail that he has developed as treatment. Carnitine has been shown to potentiate chromatin opening, and Vitamin B5 helps the body break down carnitine, so these are often helpful to children with KAT6A. Several parents have documented developmental progress in their children who are taking carnitine and vitamin B5. Dr. Kelley is quite confident that carnitine is very beneficial to individuals with KAT6A.

Dr. Bjornsson was the last speaker and he spoke about mendelian disorders of the epigenetic machinery and therapeutic possibilities. He has been studying a disorder very similar to KAT6A called Kabuki Syndrome. They are both epigenetic disorders of the histone machinery. Dr. Bjornsson is studying a mouse model of Kabuki syndrome and has been able to gain much needed information, including some effects that can be reversed using drugs targeting the epigenetic machinery. He also feels that carnitine is likely a good therapeutic treatment for KAT6A. He would like to be able to build KAT6A related data based on seeing more patients with KAT6A. He summarized by emphasizing how rare KAT6A is and that in order to assist in further research, the KAT6A Foundation needs to participate in research by donating results, samples and joining studies, as well as promote research by raising funds to help any interested lab get preliminary data to attract NIH funding. We can also continue to organize meetings and clinics such as this one and continue to increase awareness about KAT6A in the world.

The meeting concluded with some time for the families to meet, share information, and speak individually with the doctors. For those present as well as those families who were listening to the live feed, this first get-together was stimulating, rejuvenating, and gave us hope for our children’s future.

You can view the full presentations by the medical specialist on our KAT6A Foundation Youtube channel.

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Biomarker discovery in KAT6A for translation into clinical trials

For KAT6A syndrome and other neurodevelopmental disorders, researchers are starting to understand the dysregulated cellular processes affecting neurons and their supporting cells. The Chromatin Disorders Research Team at Murdoch Children’s Research Institute is currently using a mouse model, alongside human cortical neurons to study gene expression and metabolomics KAT6A syndrome, in collaboration with Professor Anne Voss at the Walter and Eliza Hall Institute of Medical Research. This work is being led by PhD student Dr Sarah Donoghue and supervised by Professor David Amor and Professor Paul Lockhart. The goal of this project is to understand the differences in brain development that occur in KAT6A syndrome, and to identify biomarkers that may show response to treatment in clinical trials.  

The team is looking to extend their work on blood biomarkers in KAT6A mice to children and adults with KAT6A syndrome. In this project, they will measure a range of molecular compounds in blood samples from human participants with KAT6A syndrome, using untargeted metabolomic and proteomic analyses. They will compare the plasma profile of 50 KAT6A syndrome participants to the plasma samples of 20 participants without KAT6A syndrome. The aim is to identify biomarkers that are detectable in the plasma of participants with KAT6A syndrome, with the hope that these can be translated for use in clinical trials, as an objective measure of treatment efficacy as the community proceeds to clinical trials.

For more information about this research, please contact Sarah Donoghue at sarah.donoghue@mcri.edu.au.

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ATTENTION RESEARCHERS:

The KAT6 Foundation is addressing a critical research priority raised by families—gastrointestinal challenges faced by children with KAT6A and KAT6B. This population experiences a concerning increase in mortality due to poor GI motility and perforation. Tragically, we recently lost another child to GI perforation, which has heightened anxiety and urgency within the community.

We are keen to better understand the factors that contribute to susceptibility to poor motility, bowel obstruction, and the risk of perforation in children with KAT6A and KAT6B. Equally important is identifying effective treatment strategies to address these serious issues.If you are interested in collaborating on this important challenge, please email the KAT6 Foundation at support@kat6a.org.

Learn more about Bowel Obstructions in the KAT6 Population.

We are proud to report that research led by Dr. José A. Sánchez-Alcázar and his team was published by Genes on November 15, 2022 in an article titled Pantothenate and L-carnitine Supplementation Corrects Pathological Alterations in Cellular Models of KAT6A Syndrome. This is an important milestone for our Foundation as it is the first research project that we directly funded to reach publication, and is an important step forward on the path to finding a treatment for KAT6 individuals. Development of surrogate models simulating KAT6A gene variation is the first step towards understanding the pathophysiological alterations caused by this gene variation. By outlining pathophysiological pathways, treatment model(s) addressing alterations in these pathways can be developed for testing.

Three individuals with KAT6A gene variation participated in the study conducted at Universidad Pablo de Olavide in Spain. An initial series of experiments generated evidence supporting the use of patient-derived fibroblast to study KAT6A gene variation. The team identified four critical pathophysiological processes altered by KAT6A gene variation: 1) Coenzyme A (CoA) metabolism, 2) Iron metabolism, 3) Enzymatic antioxidant system and 4) Mitochondrial function. Two compounds were identified to have a positive impact on the altered physiological pathways. These compounds are: 1) Pantothenate and 2) L-carnitine. Pantothenate is a CoA metabolism activator and L-carnitine is a mitochondrial boosting agent. Supplementation with pantothenate and L-carnitine supported the survival of the KAT6A fibroblast in a stress inducing medium. The concentration of pantothenate and L-carnitine varied in all three KAT6A cell lines suggesting that different type of mutations respond differently to these positive compounds. The KAT6A gene plays a significant role in histone acetylation which is a key process involved in cell progression and differentiation. Supplementation with pantothenate and L-carnitine resulted in significant increase in histone acetylation, recovery of gene expression patterns and expression levels of proteins affected due to the KAT6A gene variation.

We want to extend our sincere thanks to Dr. José A. Sánchez-Alcázar and his entire team for their professionalism and commitment to rare disease research and the KAT6 community. We look forward to building upon this partnership in the future.

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The Gastrointestinal Health and Beyond in Children with Rare Genetic Variations was a 2-hour long, patient-centered, collaborative event organized by the KAT6 Foundation. It was designed to fuel conversation about the gastrointestinal challenges faced by children with KAT6A and KAT6B gene variations and enable open dialogue between families, clinicians, and researchers. The webinar provided a platform for the KAT6 community to expand its network and build connections with new researchers and experts working on tackling GI and GI related issues. More than 90 individuals registered for this event. On the day of the webinar, 20 families and 35 scientists attended the event. With some international representation, the majority of the families and researchers were based in the USA.

Dr. Tanya Tripathi, research coordinator of the KAT6 Foundation moderated three scientific presentations by renowned scientists – Dr. Sarkis Mazmanian, Dr. Gustavo Mostoslavsky and Dr. Richard I Kelley. Please read the summary of the presentations here.

On March 24, 2022, The KAT6A Foundation hosted the second KAT6A and KAT6B Virtual Symposium.  The event was designed to solidify the KAT6A and KAT6B research network of clinicians and researchers through identification of research gaps, opportunities and collaborations. The symposium series aims to drive patient- centered and collaborative research to improve outcomes for individuals with KAT6A and KAT6B syndromes. The symposium series also aims to spark new collaborations among the KAT6A and KAT6B research groups and healthcare communities.The first KAT6A and KAT6B symposium, conducted in 2021, discussed a range of neurodevelopmental challenges faced by children with KAT6A and KAT6B gene variations. The second symposium expanded on the stakeholder representation to include parents of children with KAT6A and KAT6B gene variations along with health care professionals, clinicians, and researchers. This symposium focused on understanding the impact of KAT6A and KAT6B gene variations on speech and language development, a domain that is most commonly affected in this population of children.10 speakers and nearly 60 members of the KAT6 community attended the the symposium. The symposium ran for three hours and was organized in two sessions: the first session provided an overview of the KAT6A Foundation’s goal to empower patient-centered research and initiatives led by the Foundation to support research. The second session focused on understanding the pathophysiology of KAT6A and KAT6B related speech and language disorders.

Please read the symposium recap pdf for a complete summary of each presentation. The next virtual symposium is tentatively scheduled in September 2022. This symposium will focus on unraveling the range of gastrointestinal difficulties faced by individuals diagnosed with KAT6A and KAT6B syndromes.