About PPP2CA Pathways

Our son, Jude, had his first seizures in the Spring of 2023 when he was just three years old.  It started out as a regular day.  I was about to go to work, and Jude was about to go to daycare.  He wanted to cuddle with Mom on the couch for a few minutes before we left.  All of a sudden, he just started shaking.  It wasn't a violent thrashing.  It was more like an intense, full-body shiver.  It lasted for a minute - maybe a minute and a half.  Afterwards, he was really sleepy.  We bundled him up and took him to the hospital to get checked out.  The ER doctor ordered some tests and performed her exam.  She explained that it is actually fairly common for people to have seizures at some time in their lives.  Many people never have another one ever again.  She recommended we follow up with a pediatric neurologist on an outpatient basis.  Just as she was about to cut us loose, it happened again.  Jude started shaking right there in front of the doctor.  But something was different.  Jude turned gray over his whole body.  I was gripped by fear.  Fear that something was seriously wrong with our little boy, and I didn't know why.  It was the most frightening thing that has happened since I became a parent.  Thankfully, the physician was right there, and I put my trust in her.  Needless to say, we did not go home.  We ended up spending two days in the hospital.  During that time, Jude had dozens of electrodes stuck to his head for a video EEG.  He had to stay in the hospital bed so the camera could pick him up.  We were in a position where we didn't want him to have a seizure, but we kind of needed him to have one if the test was going to show us anything.  The day went by and we went to sleep - my wife in the recliner and me in the rollaway cot.  I don't think I slept very well that night.  Perhaps I slept lightly because we were on alert trying to catch a seizure.  I awoke in the middle of the night to my son convulsing again.  I ran to get the nurse, but all we could do was ride it out.  Three.  He had three unprovoked seizures within twenty-four hours.  This shows a predilection for cluster seizures.  We saw the pediatric neurologist in the morning.  She ordered a strong anti-convulsant called Keppra.  It knocked him out for most of the rest of our hospital stay, but at least he didn't have any more seizures.  The doctor explained that he would go home with a prescription for Keppra, and that he would have to take it for a minimum of two years.  

Over the next few months, we did more tests including an MRI and genetic testing.  The genetic testing did the trick.  We learned that Jude has a deletion in a gene designated PPP2CA that is likely pathogenic.  That's the cause of the seizures.  

Daisy’s Story: Living with a Rare Genetic Mutation – PPP2CA Daisy was born in June 2016, our beautiful second child, via planned C-section at 39 weeks. From the very beginning, she was different — though, like many parents in our position, we didn’t realize just how different right away. She was small and floppy, struggled to feed, and was re-admitted to hospital just five days after birth with failure to thrive. We were told she’d be fine, prescribed medication for reflux, and discharged. No further investigations were done. Looking back, there were signs even then: Daisy had distinct facial features — a flat nasal bridge, a thin upper lip, elfin ears, and large corneas (later diagnosed as mild megalocornea). She was quiet and didn’t make the normal baby cooing noises, cried a lot and didn’t meet typical developmental milestones. But life was moving fast — we were newly married, had just moved house, and were focused on doing the best we could. As the months passed, Daisy continued to fall behind. She didn’t sit, crawl, or walk on time. By age two, she was still completely non-verbal. When we raised concerns, we were often dismissed as anxious parents. It took persistence to be heard. Speech therapy was started, then stopped when she “wasn’t ready.” She finally walked at 26 months, with a wobbly gait and poor coordination. At three, Daisy began nursery with only a few words, much of her speech echoing scripts she had memorized (echolalia). If you asked her, “What sound does a cow make?” she’d respond, “Cows go moo,” instead of just “moo.” Her speech had a distinct, high-pitched tone and was very hard to understand. Eventually, we were referred to community paediatrics. She was diagnosed with a global developmental delay, and there was talk of possible autism. Then in February 2020, we were referred to genetics. Two years later, we received an answer: Daisy has a de novo mutation in the PPP2CA gene on Chromosome 5 — which was so rare that at that time there were only 23 cases worldwide. We only had a condition name in May 2024 when it was renamed Houge-Janssens Syndrome Type 3 (HJS3). The diagnosis was both a relief and a heartbreak. It gave us a name, but little direction. There were no roadmaps, no treatment plans, no idea of what Daisy’s future might look like. Who Daisy Is Today Today, Daisy is a spirited, imaginative and loving child. She adores her siblings and unicorns, loves anything pink and has a quirky sense of humour.  She speaks now — constantly — but her speech remains unclear to those that don’t know her and very repetitive.  She struggles to express herself clearly and becomes frustrated when others don’t understand her.  She still has significant developmental challenges. She needs help with all aspects of self-care. She has been continent since age six but still needs adult help with toileting. Her fine and gross motor skills are delayed. She has a speech impediment and is unable to make some speech sounds, and she has poor vision (she wears a strong prescription and has been under ophthalmology care for years). New Challenges: Investigating Low Blood Sugar Episodes Recently, we've encountered a new and concerning issue: Daisy has been experiencing episodes of low blood sugar (hypoglycemia). These episodes have prompted further medical investigations to determine their cause. Interestingly, emerging research suggests that the PPP2CA gene plays a role in glucose metabolism. Specifically, studies have shown that the catalytic subunit of protein phosphatase 2A (PP2A), encoded by PPP2CA, is involved in regulating insulin signaling pathways and glucose homeostasis. While the exact connection between PPP2CA mutations and hypoglycemia is still being explored, this potential link underscores the complexity of Daisy's condition and the need for comprehensive research to understand the full spectrum of symptoms associated with HJS3. Why We’re Telling Daisy’s Story We share Daisy’s story not just to raise awareness, but to call for action. Although more and more children are being diagnosed with HJS3, it is still incredibly rare.  With so few documented cases globally, the medical literature is sparse. This makes it nearly impossible to predict what Daisy’s life will look like as she grows older. We are calling on geneticists, researchers, and clinicians: we need your curiosity, your insight, and your dedication. Every child like Daisy deserves a future where their condition is better understood — not just a name in a file, but a path toward real support, therapies and hope! If research can illuminate how HJS3 affects brain development, communication, motor function, behaviour, and metabolic processes, it could change the lives of children like Daisy — and maybe others with related genetic conditions. Daisy Is So Much More Than Her Diagnosis Despite all her challenges, Daisy is vibrant and unique. She makes up silly songs. She gives the biggest hugs. She lights up when she talks about animals or fairy tales. Her condition may shape how she experiences the world, but it does not define her spirit.  She has so much to say — and we believe, with time and support, she and others with HJS3 will find their voice. We just need the world of genetics to listen.