I’ve read this story many times. Each time a different part stops me. Cold. When I spoke to Ayrana, I was awestruck by what she has been through, grateful that she is willing to share, humbled by her grace, and brokenhearted by her suffering. My analytical mind sought to analyze what went wrong, but the truth is that there is no one answer. It is a cacophony of errors. Mistakes made by numerous individuals in our medical & educational systems that do not have the experience or perspective to serve rare--medically complex--patients. The point of sharing this story is not to blame anyone, but to provide this perspective so that families, clinicians, and educators can prevent it from continuing to happen.
There are at least five stories here, packed into the first 15 years of one hard life and the lives of those who care for her.
This story is not easy to read. It is not a tale of triumph so much as a testament of survival -- but the line is blurry. It is also not over, but very much in progress: Melissa will turn 15 later this year.
Read it. A few times. Then give it to your doctors, teachers, researchers, and family. Share it out. We have to do better, and that won't happen until we look clear-eyed at what a mess our families face today.
If there is one message for parents to take away from this story, it is this quote from mom: “Some drugs have the opposite effect, some drugs barely affect her, and some she is really sensitive to… but the doctors don’t always listen.” It is true, our medically complex kids have sometimes peculiar reactions with many drugs. If you feel like your doctor isn’t listening to you, find one that does. (If they are, thank them.)
Ayrana Frazier is from Brazil, and came to the US when she was 16. She lives in New Jersey with her mother, Melissa, 4 cats and 2 dogs. She has a Masters degree in Criminology and is currently an employee of the Department of Homeland Security.
Let me start by saying this: as dark as it sounds, for the past 12 years, I have cried and prayed every day that Melissa goes a day before I do because I cannot fathom what will happen to her when I am no longer here. I do not know if that will happen. As long as I am here, I continue to work as hard as I can to ensure that she can be as independent as possible for the day when I am no longer here with her. I don't want to fail her as a parent. I cannot imagine my little girl suffering more than she has already.
Almost 15 years ago, my Melissa was born via scheduled C-section. She was born at full term and weighed almost 9 lbs. She passed all her newborn tests with flying colors before leaving the hospital. Melissa hit all of her baby milestones until 9 months old, then she stagnated. She was not making attempts to walk and she was not saying "mama" or "dada". Eventually, Melissa began walking at 18 months old, but she was still not talking. Her pediatrician insisted that everything was fine; that she was on pace with all of the other milestones, and all kids develop differently. They commented that bilingual children start talking later than monolingual children, as an explanation for her speech delay.
Our pediatrician became concerned when Melissa was 34 months. She advised that Melissa receive Early Intervention for the two months left before her 3rd birthday. Besides her delayed speech and her occasional hand tremor, there was no hint that my child had any other issues. Melissa was like a typical child—she was lovable and friendly, she would play, follow commands, make great eye contact. I was naïve. I believed, I hoped that everything was great. Or, perhaps at the time, I did not want to label my child. I could not yet consider she had a disability, so I carried on until I could not deny it any more.
Melissa was 3 when, as I was getting her out of the car, I saw her eyes begin to flicker. When I said her name, she didn't answer me. It took three times before I took her to the ER. This was the beginning of my world being turned upside down by Epilepsy.
After a few hours and many tests, I learned that these episodes were seizures. I had always been under the impression that seizures were convulsions—I never realized that there were so many different seizure types. She also had a 1 cm benign cyst on the right temporal lobe. We stayed in the hospital for about 5 days to ensure seizures were controlled before discharge.
After being discharged, we had a follow-up visit with a neurologist. Melissa was prescribed Depakote and Lamictal, both first-line anti-epileptic drugs. After a week of taking both medications, Melissa developed rashes all over her body and began vomiting, known side effects from Lamictal. The doctors replaced Lamictal with Topamax. A side effect of Topamax is cognitive delay, but nobody told me this until she was 10 (7 years later).
For the next 6 years, we had to see a neurologist every 3 months, do blood work and have an EEG every 6 months, VEEG (Video EEG) annually, as well as MRIs every 2 years. Four different neurologists tried to pinpoint what she had, but they could not identify the cause or triggers of the seizures. They could not identify an underlying disorder. All they knew was she was somewhat delayed. At one point, they even suggested that maybe I dropped her when she was little and was not being truthful. When the doctors could not figure it out, they blamed me. I felt horrible.
Melissa started school in a modified program that was 50% special education and 50% general education. We were hopeful she would catch up with these accommodations.
When Melissa was 6, her doctor gave her a diagnosis of Pervasive Developmental Disorder (PDD) so she could receive services. At this time, Melissa was not talking or making developmental progress. She was learning at her own pace, but this pace was extremely slow. She knew her ABCs, simple math, and could write her name. She could understand words in English, Portuguese, Spanish, and Italian. By third grade, Melissa's speech had improved a little. She could say a few words, but she was still not using sentences.
Melissa had always loved school, but halfway through in 4th grade, at age 10 I noticed that she started to seem somewhat reluctant to go to school. One afternoon, I received a call from her school. I was shocked to learn that Melissa was having a full-blown meltdown. When I arrived to pick her up, I was even more shocked to learn that she had been restrained by untrained personnel for about 3 hours. My child had bruises all over her body. Child Protective Services dismissed my case because I did not take her to the ER to get checked out.
She had lasting marks on her skin from the time she was forcibly restrained and I now had marks on my heart from what happened to her. These marks instilled so many emotions in Melissa and me: pain, sadness, fear, anger. I knew I had to act for her, but it would take time for me to realize the full scope of these marks on Melissa.
After this episode, I successfully advocated to have Melissa moved out of district school and have her placed in a specialized school. I believed that was the appropriate place for her. Things were good, until they were not. It would take time, but I would learn no school would be appropriate for Melissa.
At age 10, Melissa started having more challenges. She started refusing to eat and she would throw up every time we attempted to feed her. Sleep also became difficult for her. She would wake up hourly at night and sometimes she would not go back to sleep. Her behavior worsened. She had full blown melt-downs daily. At this point, we began seeing a new neurologist who referred us to a GI specialist. The GI doctor offered to enroll her in feeding therapy--but she knew how to eat, she just did not want to. We concluded her feeding problems were behavioral and Melissa's neurologist changed her medications. Topamax was replaced with Risperidone, a behavioral medication, and there was a change in Melissa.
The resulting change was like the lifting of a dark cloud. In the next year, Melissa started to flourish again. She learned how to ride a bike, swim, cook, and began to talk in full-blown sentences. And, we stayed like this for about 3 years.
At age 11, the neurologist was still puzzled by Melissa's lack of a diagnosis and ordered genetic testing. I was told that the test came back positive for a mutation in a gene called TSC2, which causes Tuberous Sclerosis. Tuberous Sclerosis is a rare disease associated with epilepsy, development delay, and benign tumors. It seemed like we had an answer. At the time I felt happy because we finally knew what was causing her problems, or at least we thought we did. At the same time I was upset because the tubers associated with TSC that I was now expecting are scary. After we learned her diagnosis, Melissa had an EKG, MRI, and an ultrasound of her lungs, kidneys, and liver looking for tumors, which all came back normal—they did not find anything.
Editors note: This was not a mistake by GeneDx, they clearly labeled this a VUS. Somewhere a clinician decided that the patient had TSC.
We kept Melissa on the same medications, which worked well until age 13 when Melissa started to eat compulsively. She gained weight. The Risperdone and Depakote together felt like a ticking bomb. She started to eat more and more, compulsively and it started affecting her health. It became so bad that we had to hide food from her. She developed high cholesterol. Also, due to the high doses of drugs, she had very high prolactin and was not not getting her period. Something had to change.
At this point, her neurologist believed that Melissa should be placed on Afinitor -- a cancer drug used to stop tumors developing in TSC patients -- and referred us to a specialist in Tuberous Sclerosis. Interestingly, the specialist was adamant about not placing Melissa on Afinitor, as she believed Melissa did not need it. (I should have listened to her.) Instead, she prescribed Zonisamide, another AED, and started to decrease the Depakote.
The Zonisamide caused vomiting and Melissa’s appetite went from voracious to non-existent. Then, in the last week of the Depakote, for the first time, she had a Grand Mal seizure. I had never felt so helpless. The neurologist concluded that this seizure was caused by the cessation of the Depakote. We went back to Depakote and replaced the Zonisamide with another AED, Trileptal. It was somewhat effective, but Depakote was essential—as soon as we tried to lower the dosage, Melissa had absence seizures again.
Puberty began. Her period was extremely painful, heavy, and long. I found a gynecologist who specializes in treating patients with special needs. After the consultation, we decided to place Melissa on birth control to lessen the intensity of her periods. I was presented with several options including the pill, patch, shot, and an IUD.
I chose the Depo-Provera shot, a long lasting hormonal birth control injection. It seemed at the time to have the least amount of side effects. Unlike the IUD, it did not require an invasive procedure nor require sedation. I was told the Depo-Provera shot could cause depression, but at the time I did not think this was likely.
Three days after the injection, Melissa became psychotic. Melissa had never needed a behavior plan, so the school staff did not know what to do with her. They restrained her to the point of almost breaking her hands. This was the second time she had been harmed at school. I immediately pulled her out and placed her in a new school.
She was expelled for behaviour after three weeks. It was almost the end of the school year and putting her in a new one so close to summer didn’t make sense. I decided to homeschool her. In 6 weeks she made great progress but started to ask why she wasn’t going to school. I put her in a summer school for 2 weeks. She was always excited to go to school, but as soon as she entered the classroom and I left, she would go full-blown psychotic for hours.
We went to a psychiatrist who helped me understand what had happened. She explained that when children with special needs have depression, it typically manifests as aggression. The Depo shot had likely caused the behaviours at school. The psychiatrist diagnosed Melissa with an anxiety disorder and Post-traumatic stress disorder (PTSD) . I learned that she had been traumatized when she was inappropriately restrained at school. The resulting PTSD led to increasing anxiety and then more aggression in the school setting. To help with her anxiety, the psychiatrist prescribed an anti-anxiety medication called Lexapro.
In September, she started as a special school where she remains now.
In September, Melissa's neurologist referred us to another epileptologist who specialized in Tuberous Sclerosis. This neuro recommended that we place Melissa on Afinitor to prevent lung tumors, which was a risk for teenage patients with TSC in their teenage years. We gave her Afinitor to be proactive, even though an earlier doctor had advised against it. How is a parent supposed to navigate when all these doctors have different opinions?
After a month of taking Afinitor, Melissa behaved in a way that felt suicidal. Just before Christmas, Melissa and her grandmother were out shopping. Without warning, Melissa ran out towards the street and laid face up, all while screaming, laughing, and trying to take her clothes off. When people tried to help her, she hit them away. Melissa went to the ER in an ambulance.
At Overlook Hospital, they put restraints on Melissa’s arms and legs. I started arguing with the doctors, I told them that she was not a criminal. They had security remove me from the room and they threatened to call the police. I remember that day as the day I almost went to jail.
Since that Christmas day, I've lost count of how many times Melissa has been taken to the ER by ambulance, restrained and sedated. One time, they took her in the back of a police car, in handcuffs.
This became our horrible new normal. I stopped arguing. I would tell the paramedics that it needed to happen, and then leave the room. As much as it hurt me, I knew it was necessary. During these manic episodes, Melissa went in and out of her normal self. She would respond normally to a question and then, a moment later, be manic again. Doctors would attempt to sedate her, but it would not work.
This pattern of ER, drugs, and manic episodes had to stop. The drugs were not working. At my request, the specialist agreed to place her on Epidiolex, but we needed insurance approval. In February 2020, after a VEEG, Melissa came home with a new medication plan: Onfi (epilepsy medication, a benzodiazepine), Lexapro (anxiety medication), Risperidone (behavior modifying medication), and Abilify (mood modifying medication for depression). The plan was to remove the Risperidone and Onfi when the Epidiolex was approved.
When COVID-19 hit, we were just beginning to remove the Risperidone and increase the Abilify. My state was mandated to quarantine. For two months, I isolated Melissa and my mother from everyone. She was not allowed to go out, and no one allowed in. Melissa began to regress cognitively
Melissa's personality shifted, almost split, in the isolation. She started to talk to herself as if there was someone else with her, or better yet, another Melissa. I would hear her say, I’m going to break the TV. Melissa don’t do it, Mommy will be mad. Yes, do it. No, don’t do it, bad girl. And then she would hit herself. Or she would hit herself and scream at herself to stop.
She became hyperactive as well and her meltdowns were worsening. She would not stand still for more than a minute at a time, she could no longer watch a movie, or play on her iPad. She would sit and then a minute later, she would jump out and run. Melissa’s meltdowns, which she would typically get around the time of her period, were increasing in intensity and length.
After hearing about all of the changes that Melissa was experiencing, her psychiatrist advised me to keep her on the Risperidone until things got somewhat back to normal. It would be safer to not reduce the Risperidone while in isolation due to these dramatic personality changes. We didn’t know if her behavior was related to side effects of her medications or all the changes brought about by the pandemic. Despite keeping her on the Risperidone, Melissa’s behaviors worsened and became mania. Every time we got in the car, she would get anxious and try to open the car door, sometimes trying to jump out in front of cars in an attempt to escape the confined space. In response, her psychiatrist increased her medication.
At one point, Melissa was on 6 mg of Abilify once a day and 2 mg Risperidone 3 times a day. Yet, her behavior was getting worse and worse. How were we giving this child all these medications and they weren’t helping? I was so consumed managing the crisis, I didn’t have the time to articulate these questions. For two months we were just in damage control mode, day and night. We were zombies.
Melissa’s care team and I were all puzzled on how my child could be on such heavy doses of two powerful antipsychotic medications, one anxiety medication, and a benzodiazepine- but was still having all of these behavior issues. One day, she tried to escape again, and I took her to the ER. Melissa was given a dose of a different benzodiazepine this time called Lorazepam. The Lorazepam made her even more anxious and agitated. She needed a dose of an antipsychotic called Haldol and that is when we discovered that benzodiazepines did not work for Melissa. That’s when I learned that, for some patients, including Melissa, Benzodiazepines have “paradoxical reactions.” Instead of calming the patient, they could actually cause anxiety or psychosis. Onfi, one of her daily medications at the time, is a benzodiazepine.
One of Melissa’s doctors expressed some skepticism about her diagnosis of Tuberous Sclerosis (TSC). Melissa didn’t have any of the typical symptoms of TSC, like tubers, angiofibroma, or tumors. He requested another genetic test. We thought little of it, our focus was on meds. But this is how genetic tests are, you give a sample and move on to help your medically complex child, never stopping to think about what results might come and what they might mean.
While we were in isolation due to COVID-19, we were fighting for insurance approval for Epidiolex. After 4 insurance denials and five long months of fighting to get it approved, we finally won. We were supposed to start slowly. During the first week, we started at 1.1 ml, with no issues. The second week coincided with the week of her period, and we increased to 3.3 ml. Things were touch and go, but meltdowns were expected. In the fifth week, we increased to 5 ml. All hell broke loose.
Melissa became a new type of psychotic. This was worse than the Depo-Provera triggered episode. For the first time, she became violent and destructive. She started hitting my mother. She started hitting me. She would throw and break furniture. She would throw chairs at us. This happened every day, from 2 pm to 8 pm, like clockwork, nonstop. There was nothing that triggered her. One second she was calm and then the next, she would throw her iPad across the room and then she would come after one of us. Anything and everything she could put her hands on she would throw.
After an entire month of enduring this behavior, we became desperate. I spoke to her psychiatrist begging her to give us another medication. She refused. She wanted Melissa to get another VEEG in July 2020 and then revisit the discussion on medication. The day of the VEEG could not come soon enough.
In mid-July, four days before Melissa’s long anticipated VEEG, I received a phone call about her recent genetic test--the Invitae Epilepsy Panel. The panel had come back with unexpected results: a pathogenic diagnosis for SYNGAP1.
It was at that time I realized that the original genetic test from GeneDx said she has a variant of unknown significance (VUS) for TSC. But for some reason our clinicians treated it as if it were certain, and as if she had TSC. That ultimately led us to put Melissa on unnecessary medications such as the Afinitor, a tumor medication. So, while I felt relieved that we had a diagnosis that fit everything, I was extremely frustrated that the original misdiagnosis of TSC had led us to take measures that we now know were unnecessary.
Four days later, we were admitted to the Hackensack Hospital in order to get the VEEG. The first day went well, Melissa was happy and calm, but she was also adamant that it was time to go home. Usually, Melissa loves staying in hospitals, going to doctors, and getting blood work done. This time she tried to escape.
It took six hospital security officers to stop her; she was restrained and sedated. But the sedative drug was ineffective, to the amazement of the hospital staff. They tried for three days. Then I learned that the medication they had been giving her was Ativan, which is just another name for Lorazepam, a benzodiazepine. If they had studied her records they would have known the negative effect this would have on her. They switched to Haldol, but after 4 days, of restraint, sedation or both, the damage had been done.
Then, to add insult to injury, the resident doctor informed me that his floor was not equipped to handle Melissa. She was cleared by the neurologists and the pediatrician, but not by the hospital psychiatrists--who had given her a drug we knew didn’t work, which caused psychosis. I then received a phone call from a psychiatric facility two hours away from my house, informing me that Melissa`s bed was ready.
I have never felt the terrible desperation caused by that call before.
I knew I had to be strong; I had to find a way to get her home. I begged the psychiatrists to let me take her home, but they refused. I tried to explain that her behavior was because she just wanted to be in a familiar place. They told me they would give me 24 hours, and that only if she was calm could she go home. I prayed, and I prayed. We kept telling her she was going home & they sedated her. This did the trick. She calmed and the next day we were allowed to go home.
Melissa was discharged with half of the dosage of Onfi and Lexapro that she was taking before, and the psychiatrists also prescribed Geodone, a new antipsychotic medication, and Depakote. I was under the impression that when we got home, everything was going to be fine. I was wrong. After 10 minutes in the car, Melissa kicked the seat, tried to open the door, and attacked my mom. I was on a mission to bring this girl home. I don’t know how, but we got there.
From that day onward, until 10 days before I wrote this, my life consisted of Melissa hitting my mom and me, hitting the animals, attempting to start the stove, throwing things everywhere, and breaking things. She cut my mother's face open and dislocated my toe. We are covered with bite marks and bruises.
As much as Melissa is fighting us and herself, I am determined to fight for her. She is not only going through all of the side effects of the anti-epilepsy medications, but she is also dealing with psychosis, anxiety, and cold-turkey withdrawal from Risperidone, Abilify & Epidiolex as well as decreases to her other meds: Lexapro & Onfi. They also added Geodone and Depakote. In the long run, these were good choices, but doing them all at once was tough.
I kept asking the doctor for an “as needed” dose of Risperidone, but she refused. The doctor told me that if Melissa had another meltdown, I would have to admit her into a psychiatric facility.
We blocked off the majority of the house, only allowing her to go to the bathroom, her room, kitchen, and my mother’s room. We removed everything that could hurt her—the TVs, silverware, furniture—we kept only our beds. I stopped working, but this was not sustainable.
The two months of fighting her every waking moment pushed me to a point where I had nothing left. Things were not changing or getting better. I started to question if I was the right thing for her -- she needed more than I could give. I called Emergency Medical Services and they took her. The paramedics already knew her, they had been there the day before. I called and told our doctor my fear that, if we continued like this, my child would hurt me or I would hurt her. I could not allow this to happen. My home was not the right place for her now.
A social worker got involved and started to try to find a facility to place her for medication management. Melissa needed a one-on-one caregiver, and none of the facilities close to my home had the capacity to care for her needs. The only facility that could accept her was the place two hours away from my house. The facility staff told me that they would have her picked up and transported to the location, and I would be unable to ride with her in the ambulance or follow behind to see the facility. Melissa would have to stay for a minimum of 20 days. She would have a one-on-one caregiver most of the time, but she would also have a roommate. I almost died that day as I imagined Melissa going away.
All I had in mind was my little girl, surrounded by strangers, asking “Where is Mommy?” Sometimes Melissa does not remember what happens during her meltdowns; one day, after she broke our door, she asked me “What happened?” I also worried that if I sent Melissa away, the experience might traumatize her further, and I might never have my baby back.
I decided that I was willing to endure the aggression, as long as she was home. I was going to find a way.
I begged the doctor to prescribe Haldol, telling him that she was experiencing withdrawal and that I was certain she would be fine in a few days. He was a Godsend and gave me the medication for 5 days. I also got an additional 15 days from her psychiatrist. I did have to give her Haldol a few days—mostly giving her a quarter or a half pill, and only twice a whole pill. I also gave her Benadryl, to calm her down.
This brings us to the present day. Now she is only on 5 mg of Lexapro (which is half of what she was taking before), Depakote and Geodone twice a day. The aggression from before has been replaced by calm and focus. As long as we don’t leave her alone, because it only takes a moment for her to turn, and if she turns, it’s impossible to get her back. Ever since the Depo shot she does this thing where her pupils get huge and it is as if we are dealing with another person. This is what I mean by “turning” it is so hard.
We are constantly redirecting her, reminding her of things she likes, as a result fewer things get broken. She has started to have seizures again since she is only on Depakote, but this time they are different: a combination of paralysis and jerking movements, with an eye twitch.
Melissa’s anxiety is extreme. She is fearful of many new things now such as the rain. The rain induces an anxiety attack now. Showers too have become anxiety inducing for Melissa. There are days that we try for hours to get her to shower without success. My mother gets frustrated, but I tell her to pick and choose our battles. Some days, we make do with baby wipes in lieu of a shower. At least she is home, where she belongs, and not trying to hurt us or herself.
Melissa continues to have problems sleeping and she has developed new compulsive behaviors. We give her melatonin every night, but she wakes up throughout the night multiple times. She will seek out my room or my mother’s where she can relax and go back to sleep. She has some compulsive behavior: right shoe on first, wash left armpit first, light switch off then on then off. If you ask her to get something, and somebody else brings it, she will take it back to its original place and then bring it to you. She also has tics, which started a few years ago.
These days I need to be careful with texting. It has become a trigger for her when I pick up my phone. She’s afraid I’m going to call 911.
Melissa can understand and speak (within her limits) three languages: Portuguese, Spanish, and English. You can prompt her on all three and she will answer or act upon it. Her verbal skills have come a long way, but she struggles to read. I’ve noticed that her seizures can be brought on by her attempts to read, even when normally controlled by medication.
Some of Melissa’s quirks and affections have not changed. Melissa continues to be picky when it comes to food. She will eat the same thing for 6 months and then she changes to something else. She is still fascinated by electronics and enjoys certain TV episodes that she can watch over and over again.
When she speaks, she makes strong eye contact and she loves hugs, kisses, and any sort of physical contact from her loved ones. I’ve even seen her blow kisses to boys. Before the onset of her psychotic episodes, Melissa, her grandmother and I, would go to museums, restaurants, parks, or Chuck E. Cheese weekly. We would travel at least twice a year, and during the summer, we would go to Six Flags with my mother. I hope that we can do these things again some day soon.
I know there will be a day where I will have to place her somewhere. But I would like to place her in residential living, not into a psychiatric facility, and on our terms. It is my mission that this day will not come anytime soon. Right now, all I want is for her to have some peace. I need her to have the same peace she had when she was younger, because my poor girl is lost right now and I don’t know how to help her.
Once we had the SynGAP diagnosis, I reached out to an online SynGAP support group. It was July when I connected with SRF. Peter put me in touch with the SRF ambassador for my state. She spent hours with me. She connected me to a leading NY Epileptologist who sees SynGAPians. She was a support when I was desperate. She is a Godsend. I am very grateful for all her help.
The first 15 years of Melissa’s life have been hard. The reason SRF exists is so that the rest of it doesn’t have to be.
Science is moving fast and we are hopeful that the labs and companies looking at SynGAP will bring therapies to the market in a few years. Indeed, we are standing up a digital natural history study right now in order to make sure these treatments can move through clinical trials as fast as possible. But trusting the existing efforts to “cure” patients is nor enough.
As parents who love their children diagnosed with SynGAP, we are doing everything we can to accelerate translational science towards precision therapies. This is why SRF funds leading scientists, both those who are established in the gene and newcomers with expertise in areas that we need.
When will our work be done? Only when there are precision therapies for our loved ones, so we don’t have to subject them to litany of side effects, titration challenges, and medication errors that Melissa’s story makes so clear. Only when the thousands of girls and boys, men and women, with undiagnosed SynGAP, just like Melissa, are identified and treated. Only when this disease (and its treatments) stops sapping savings, testing marriages, exhausting parents, and traumatizing, limiting, and holding back those whom it affects.
Until then, at SRF—those of us who have a loved one with SynGAP—don’t have a choice: we know our children are mighty and this disease is horrid. We will keep working with scientists, mobilizing resources and telling our stories until our kids get better.