Congenital CMV story

Courtesy of my daughter

Jess Markins' daughter was just a little over 24 hours old when her whole world was rocked.

The mom and content creator, who has been sharing her 2-year-old daughter Caroline's journey on TikTok, tells PEOPLE that she first learned that something might be wrong with Caroline during her pregnancy at her 20-week anatomy scan.

"Doctors noticed growth restriction and some abnormalities on the ultrasound," she explains. "We went through additional testing and very close monitoring for the rest of my pregnancy, but I was mostly told that she was just small."

Markins says that she was told Caroline would be evaluated more thoroughly once she was born, since nothing stood out strongly enough to give a clear diagnosis. And for the first 24 hours of Caroline's life, everything was relatively normal.

"After that, everything changed. A routine brain ultrasound showed calcifications, and she was diagnosed with microcephaly," says Markins. "That led to an MRI, which revealed more extensive abnormalities in her brain."

"Around the same time, she failed her newborn hearing screening. Because of [the state of] Virginia's guidelines, that meant she needed to be tested for congenital CMV — something I had never even heard of before."

According to the CDC, cytomegalovirus (CMV) is a common virus that infects people of all ages. However, when a baby is born after being infected with CMV during pregnancy, it is called congenital CMV. About 1 in 200 babies are born with congenital CMV infection, and about 1 in 5 babies with congenital CMV infection will have birth defects or other long-term health issues.

"When Caroline was one week old, we got the results: she tested positive for congenital CMV," says Markins. "My first reaction was fear — there were so many unknowns. I clung to the hope that she might be one of the children who test positive, but remain asymptomatic.

But as Markins and her partner Chris began meeting with specialists, it became clear that Caroline was symptomatic and would need significant medical support. She began antiviral medication during her first weeks of life, and early intervention began shortly after. Caroline had physical therapy at 2 months old, occupational therapy at 6 months and speech therapy by her first birthday.

"At first, I think I was in a bit of denial, hoping things might not be as serious as they seemed," she says. "But I also knew that giving Caroline every available resource could only help her. Early intervention became something I was incredibly passionate about right from the start. Even in the middle of fear and uncertainty, I knew action was something I could control."

Now two years later, Caroline's days are very structured. Markins says her daughter gets up very early — sometimes around 2 a.m. — and will watch a few TV shows while she tries to sleep a little more. They officially begin the day at 6:30 or 7 a.m., where Caroline gets her first G-tube (gastronomy tube) of the day.

"Caroline sees multiple specialists and has therapy every week, so some days are very busy and involve a lot of driving and time at clinics," says Markins. "On days we're home, we focus on movement and play. She spends time stretching, using her swing and doing floor activities like assisted sitting and rolling."

"She also uses supportive equipment like her activity chair and stander, depending on her energy level that day. Throughout the day, we incorporate her eye-gaze device so she can communicate and make choices," she continues.

Caroline is able to communicate through her eye-gaze device, which is a form of augmentative and alternative communication (AAC) that uses eye tracking. She can select words or phrases on a screen by just looking at them.

"Her communication journey has been incredible to watch. We started when she was about a year old with simple buttons, which gave her very limited ways to express herself. But the more she worked in speech therapy, the more we realized she had a lot to say," explains Markins.

"We moved to picture boards, where she began communicating with her eyes, and as she got older, she had a formal eye-gaze evaluation. She did so well that she now uses her eye-gaze device as her primary way to communicate."

Markins says that Caroline's vocabulary is "constantly growing" and that they are always adding new words and updating her device to match her growing interests and personality.

"And trust me, she has a big personality. Caroline is funny, sassy and very opinionated," says the proud mom. "If you don't understand what she's saying, she will absolutely repeat herself until you do."

Right now, Markins says some of her daughter's favorite things to say are "watch" followed by the name of a television program, and she's been asking for "drink water" because she enjoys taking small sips by mouth.

Caroline also has an About Me page on her device, where she can share her name, age and birthday. Markins says Caroline loves to tell people all about herself, and adds that her favorite button right now is "big news." She's set to become a big sister this summer.

"She tells anyone and everyone, and she is so proud and excited," says Markins.

When they don't have the eye-gaze device, Markins and her family use head taps to help her make choices. But even without any tools, she says that Caroline is incredibly expressive.

"You can see what she's feeling just by watching her face. Her smile is warm and contagious, and she makes it very clear what she thinks," says Markins. "For us, communication is about giving her as much autonomy and voice as possible — and watching her personality shine through has been one of the greatest gifts."

Throughout this journey, Markins says she and her husband have been very fortunate to rely on a strong support system around them. Both of their families live within 30 minutes, and they've been leaning on their local community recently.

"We’re currently fundraising for adaptive equipment and a wheelchair-accessible van for Caroline, and the way people have rallied around her has been overwhelming in the best way," she says. "Seeing how much love and care people have for her truly blows me away."

"Day to day, my husband is my biggest teammate. He works incredibly hard — seven days a week — to support our family financially so I can stay home and be Caroline’s full-time caregiver and be present for both of our girls," she continues. "That kind of partnership makes everything we do possible."

Caroline also has a big sister named Emersynn, who is only 13 months older than her. The two sisters have grown up together, and Emersynn has never known life without medical equipment, therapy visits and extra care for Caroline.

"What amazes me most is how naturally Emersynn has adapted. From the time she was very little, we never had to constantly tell her 'don’t touch' or worry about her interfering with Caroline’s equipment," says Markins. "When Caroline had feeding tubes taped to her face, Emersynn didn’t pull at them. With her feeding pump or medical supplies, she’s always been curious but respectful. Even with Caroline’s hearing aids, she asks questions but doesn’t try to grab or remove them."

"Emersynn just wants to be involved. She watches closely, asks questions, and cheers Caroline on in the sweetest ways. When Caroline uses her eye-gaze device, takes a sip of water, or activates a toy, Emersynn is right there clapping and cheering her on. She is truly one of Caroline’s biggest supporters."

Since sharing Caroline's story on TikTok, Markins says she's found a community online from other parents who are walking the same path as her. She's also been able to advocate for her daughter and provide an example of a medically complex and disabled child.

"When Caroline was first diagnosed, I found myself searching for other parents who were living this kind of life. Watching medical moms and disability parents share their experiences made me feel less alone," Markins tells PEOPLE. "Seeing how they adapted their homes, routines, and expectations to give their children full, meaningful lives was incredibly powerful for me."

"At some point, I realized I wanted to be that person for someone else. I wanted to be the mom I wish I had been able to watch when I was newly navigating diagnoses, equipment, and a completely different version of parenthood than I had imagined," she says. "There’s also such a lack of representation for medically complex and disabled children. Our world is built for able-bodied people, and families like ours often have to fight and advocate just to access basic opportunities."

Markins says she feels a responsibility to share their family's story to help create more awareness, more understanding and more inclusion for kids like Caroline.

"I want people to see that disability is not something to hide away — it’s a part of life, and these children deserve to be seen, supported, and celebrated," she says. "I would choose Caroline in every lifetime, a hundred times over. What I would change is not her — it’s the way society views and supports people with disabilities. If sharing our story helps even one person better understand or shift their perspective, then it’s worth it."

Hannah Sacks

https://people.com/2-year-old-girl-communicates-with-eye-gaze-device-exclusive-11913019

Compassion in the UK

February 5

Dear Shmuly,

Today we attended a full-day meeting to work out the legal aspects surrounding your care. Here in England, they don’t place a high value on life that isn’t “productive.” Under UK law, if a patient is dependent on life-sustaining treatment without the prospect of significant recovery, it’s often judged to be not “in their best interests” to continue. These life-or-death decisions end up in the hands of NHS trusts and the courts. So even though every breath you took — with the help of the ventilator — meant the world to us, we knew we wouldn’t be able to fight the NHS forever.We didn’t want a court case, so Tatty and I, along with our legal team, went to many meetings as we tried to work out an agreement with the hospital administration through the courts.

Today I had to join an in-person meeting.

Last night I slept at home and noticed an empty picture frame I’d bought before Tatty and I got married. The placeholder paper read: Today is a good day. And I thought, Today is a good day, but tomorrow can’t be.

But tonight, after ten long, long hours of discussion, migraines, exhaustion, and the brick wall of a quickly-going-nowhere back-and-forth, I looked at that frame again and realized: Good is relative. Our situation isn’t great, and it looks like we’re going to have to take your case to court, but there are moments of goodness and even humor and laughter laced through all the frustration.

I’ve tried to notice the small hugs Hashem sends. That moment of sunlight on your face. The nurse who gave me a birthday card with your footprints. The friend who texts at exactly the right time.

Small hugs, but when I look for them, I find them.

Love, Mommy

June 30

Dear Shmuly,

The court process dragged on longer than we expected; hearings were postponed, and dates kept getting moved as we struggled to reach an agreementabout your long-term care — with the hospital denying that you had quality of life, and we insisting that your very existence was valuable.

First the hearing was pushed off until after Pesach. Then after Shavuos. When I heard about the latest delay, I said, “It looks like Shmuly’s going to livethrough all the Yamim Tovim!” It was another hug from Hashem, a confirmation of your life.

But I knew the end was coming, and instead of feeling robbed, I felt grateful. You could have died right away, Shmuly. Or much earlier. Every extra day was agift. And we chose to accept it.

The finalized legal decisions included one week so we could say goodbye properly. The family came. Grandparents. Siblings. Aunts. Uncles. Friends. Wecaptured those moments with you.

But the uncertainty was crushing. We didn’t know what would happen once the ventilator was removed. Would it be peaceful, or would our time together bepunctuated by alarms ringing as you struggled to breathe? Would it be minutes? Hours? How long would we have to cherish the last few moments?

Nothing was certain. But I bought you a final set of soft, cuddly pajamas, and you stayed in them until the end.

By the time Monday came, I was prepared — at least intellectually — to give you back. Nothing could prepare my emotions. The pain I carried in my heartwas excruciating, stealing my breath at the thought of losing you. But we’d been living in the shadow of this goodbye for months, and I wanted the momentto be as perfect as possible. Tatty and I were in the room with you, and everything was calm and gentle.

The hospital wanted to extubate you, but doing that could have caused you to die immediately. We needed to make sure you had a chance, so we worked tocreate a plan that would reduce your support gradually and safely. With the help of our supporters, the court honored the Torah way of doing this transition,avoiding immediate death.

The doctors switched your ventilator to a CPAP mask (a machine that gently pushes air into your lungs to help you breathe) and helped keep your airwayopen. They reduced your breathing support slowly and carefully, only when they thought you could handle it.

In the end, you surprised everyone, Shmuly. You breathed on your own for nearly ten hours.

For the first eight hours, you were perfectly calm. I held you the entire time, listening to each breath. For the first time since you were a newborn, I could seeyour whole face… no tubes or machinery covering you. And that’s the picture I remember.

One striking detail about your life is that the timing of your birth, cardiac arrest, and passing, all took place at night, the start of the new Jewish day. Every dayof your life was complete. The 16 days before the hospital and the 307 days in the hospital, 323 days in total, were all whole.

In the final two hours, you struggled for breath. I held your hand and stroked you as the sun set and the sky turned pink behind you. I whispered Shema,faltered through Hamalach, and sang softly.

And then, peacefully, you passed away.

I was there the whole time. I was always there.

We fought for you all the way, Shmuly. And in the end, you fought for yourself.

Love, Mommy

See: https://mishpacha.com/23-million-seconds/

Miracle on ice

Awesome World ·

Stuart Handel

In December 1980, a young woman named Jean Hilliard, just 19 years old, was driving home through the bitter cold of Lengby, Minnesota. The temperature that night plunged to a brutal –30°C (–22°F). When her car slid off the icy road and stalled, she decided to walk through the snow toward a friend’s house nearly two miles away.

But only 15 feet from the door, Jean’s body finally gave in to the cold. She collapsed, unconscious, and remained there for six long hours, her body completely frozen solid by the time dawn arrived.

When her friend discovered her the next morning, Jean’s skin was stiff as wood, her eyes glassy, and her body too frozen to bend. Even hospital thermometers couldn’t register her temperature. Doctors had little hope.

Yet, they refused to give up. They wrapped her in warm blankets and slowly raised her body temperature with heating pads. Hours passed — then something incredible happened. Jean’s body began to soften. Her pulse faintly returned. Against all odds, she woke up.

After 49 days in the hospital, Jean not only survived but made a full recovery — with no brain damage or amputations.

To this day, her case remains one of the most extraordinary medical recoveries ever recorded — a story that continues to remind us that even when life seems frozen beyond repair, miracles can still thaw the impossible.

Comment

Bangsar Fan

Grok Fact Check: Fact Check: Jean Hilliard’s Hypothermia Survival
The story of Jean Hilliard’s 1980 survival in Lengby, Minnesota, is mostly true. On December 20, 19-year-old Jean’s car skidded into a ditch in –30°C (–22°F) weather. She walked ~2 miles toward a friend’s house, collapsing 15 feet from the door. Found after ~6 hours, her body was rigid, pale, with a core temperature (~27°C) too low for standard thermometers. Doctors at Fosston Hospital used blankets and heating pads; she awoke hours later, defying grim odds. After 49 days in hospital, she fully recovered with no brain damage or amputations.
Accuracy: 95%. “Frozen solid” is slightly exaggerated (faint pulse remained), and distance is approximate. Verified by Montreal Gazette (1980), MPR (2018), Snopes (2015). A rare hypothermia survival case.

https://www.facebook.com/groups/988897155023132/posts/1914787879100717/

Sameer Karthik

Kind hearted psychopath9y

What are some weird facts?

In 1980, a woman named Jean Hilliard in rural north western Minnesota, was involved in a car accident which resulted in car failure in sub-zero temperatures. She walked to a friend's house 2 miles away and collapsed 15 feet outside of the door. Temperatures dropped to −22 °F (−30 °C) and she was found "frozen stiff" at 7 a.m. after six hours in the cold. She was transported to Fosston Hospital where doctors said her skin was too hard to pierce with a hypodermic needle and her body temperature was too low to register on a thermometer. Her face was ashen and her eyes were solid with no response to light. Her pulse was slowed to approximately 12 beats per minute.

She was wrapped in an electric blanket.

The miraculous thing that happened was, 49 days after she was admitted, she was discharged from the hospital with no permanent damage to the brain or body besides frostbite.

Some people might be wondering how this was possible, but scientists explained this :

There's at least one possible scientific explanation.

In the article "Is Human Hibernation Possible," published in 2008 by the Annual Review of Medicine, Dr. Cheng Chi Lee of the University of Texas' Department of Biochemistry and Molecular Biology notes that

"Some mammals can enter a severe hypothermic state during hibernation in which metabolic activity is extremely low, and yet full viability is restored when the animal arouses from such a state."

In a search for therapeutic uses of induced-hypothermia, Dr. Lee found a "natural biomolecule," 5' AMP, that "allows rapid initiation of hypometabolism in mammals" and that

"may eventually result in clinical applications where hypothermia has been shown to have tremendous lifesaving potential, such as trauma, heart attacks, strokes, and many major surgeries."

It is possible that Hilliard froze so quickly that her body skipped the phase where lasting tissue damage could be done and her body entered a hypometabolic state that allowed her basic life functions to continue until she was successfully thawed out.

https://www.quora.com/topic/Jean-Hilliard-1?q=jean%20hilliard

Lee CC. Is human hibernation possible? Annu Rev Med. 2008;59:177-86. doi: 10.1146/annurev.med.59.061506.110403. PMID: 18186703.

Abstract

The induction of hypometabolism in cells and organs to reduce ischemia damage holds enormous clinical promise in diverse fields, including treatment of stroke and heart attack. However, the thought that humans can undergo a severe hypometabolic state analogous to hibernation borders on science fiction. Some mammals can enter a severe hypothermic state during hibernation in which metabolic activity is extremely low, and yet full viability is restored when the animal arouses from such a state. To date, the underlying mechanism for hibernation or similar behaviors remains an enigma. The beneficial effect of hypothermia, which reduces cellular metabolic demands, has many well-established clinical applications. However, severe hypothermia induced by clinical drugs is extremely difficult and is associated with dramatically increased rates of cardiac arrest for nonhibernators. The recent discovery of a biomolecule, 5'-AMP, which allows nonhibernating mammals to rapidly and safely enter severe hypothermia could remove this impediment and enable the wide adoption of hypothermia as a routine clinical tool.

Service above and beyond the call of duty

 My name is Jessica, and I’m the mother of two amazing girls, an eight year old and my youngest, Madelynn, who is five. Madelynn is a true warrior. She has a bravery far beyond her years and the purest love for rollercoasters, Disney, and stuffed animals. As a family, we love spending time together, swimming, skiing, and playing board games. But behind our happiness is a daily battle that quietly shapes our lives. 

Madelynn was born with Tuberous Sclerosis Complex (TSC), a rare disease that causes benign tumors to grow in her brain, heart, kidneys, face, and eyes. We didn’t receive her formal diagnosis until she was 15 months old. Shortly after, her EEG showed sharp waves, an early warning sign that seizures were likely. Madelynn had her first seizure at age two. It was so severe that she had to be medevacked to the hospital. I remember every second of those 12 minutes, 12 minutes where we didn’t know if she would wake up. It was the worst day of my life. 

Since then, Madelynn has been on two anticonvulsion medications, including one we receive from PANTHERx, and she has been seizurefree for three and a half years. But missing even one dose could trigger another medical emergency. Status epilepticus, when a seizure lasts longer than five minutes or when seizures happen back-to-back it can be life threatening. There is nothing more terrifying than not knowing if your child will be okay. 

That fear became very real during a recent fun family ski trip. 

Madelynn takes six medications every day. Packing for travel is a meticulous process, syringes, pills, liquids, powders, and always her rescue medication. Despite  double and triple checking, one of her medications was left at home on the kitchen counter. And of course, it was the one medication we can only get from PANTHERx. I didn’t discover the mistake until Friday night when I went to give her evening dose. 

Upon discovering the missing medication, I knew immediately that we would have to end our trip and drive home, there was no way I could risk her missing that dose. 

Out of desperation, I called PANTHERx in a panic, barely able to speak through my tears. The woman on the phone was incredibly kind. She told me she would do everything in her power to help. 

We tried every possible option. Overnight delivery wasn’t possible—FedEx had stopped taking shipments. A friend back home couldn’t ship it because the FedEx location wouldn’t accept medication. And with FedEx closed on Sundays, nothing could get out the next day. PANTHERx even called local hospitals for alternatives. 

Then, when I was running out of hope, I got a call back.

They told me they had secured a courier who would drive six hours through the snow to deliver the medication directly to us. 

I cried. I couldn’t believe they were willing to do that for my family. I even offered to pay, but they told me they were simply happy to help a mom in need. That courier drove for hours on a weekend, in the snow to make sure my child didn’t miss a dose. 

As a mom of a child with complex medical needs, I live with constant worry. You never sleep the same way. But in that moment when I was scared, PANTHERx stepped in without hesitation. They’ve always been incredible. When Madelynn first needed medication and insurance hadn’t approved it yet, they sent it at no cost because she needed it immediately. 

If I could say anything to the team that helped us that weekend, it would be this: Thank you for helping me when you didn’t have to. Your kindness was above and beyond, and I will never forget it. 

To other families, I want you to know that there truly are good people in the world. I’m so grateful I made that phone call. I only wish I could get all of my daughter’s medications from PANTHERx. 

They didn’t just deliver medicine. They delivered peace of mind when I needed it most! 

https://pantherxrare.com/rarestories/a-vacation-saved/

AAV9 gene therapy in Type II GM1 gangliosidosis - A phase 1-2 trial

Lewis CJ, D'Souza P, Johnston JM, Acosta MT, Farmer C, Baker EH, Crowell A, Mojica Y, Ashraf S, Joseph L, Vézina G, Quezado Z, Yousef MH, Vardar Z, Shazeeb MS, Corti M, Blackwood M, Coleman K, Batista R, Thurm A, De Boever E, Gahl WA, Byrne BJ, Flotte TR, Jiang X, Gross AL, Keeler AM, Gray-Edwards H, Martin DR, Sena-Esteves M, Tifft CJ. AAV9 Gene Therapy in Type II GM1 Gangliosidosis - A Phase 1-2 Trial. N Engl J Med. 2026 Feb 6. doi: 10.1056/NEJMoa2510935. Epub ahead of print. PMID: 41665410.

Abstract


Background: GM1 gangliosidosis, caused by biallelic variants in GLB1, results from deficiency of lysosomal β-galactosidase, which degrades GM1 ganglioside. This fatal neurodegenerative disease currently has no effective therapy.

Methods: In a phase 1-2, open-label, dose-escalation study, we assessed immunosuppression and a single intravenous infusion of adeno-associated virus serotype 9 (AAV9) encoding β-galactosidase in children with type II GM1 gangliosidosis with late-infantile or juvenile onset. The primary end point was safety. Secondary end points included changes from baseline in the cerebrospinal fluid (CSF) GM1 ganglioside concentration and β-galactosidase activity, clinical assessments (including the Clinical Global Impression-Improvement [CGI-I] score, assessed on a scale from 1 [very much improved] to 7 [very much worse]), and neuroimaging patterns.

Results: Nine participants were enrolled. Over a 3-year period, 124 adverse events occurred, 30 of which (8 gastrointestinal events, 21 laboratory abnormalities associated with inflammation, and 1 tachycardia event) were deemed by the investigator as being possibly, probably, or definitely related to the gene therapy. Five serious adverse events occurred, including vomiting that led to hospitalization in one participant, which was attributed to the gene therapy. Serum aspartate and alanine aminotransferase levels increased in all participants and returned to baseline levels by 18 months. In all participants, the CSF β-galactosidase level increased and CSF GM1 ganglioside level decreased. Expressive communication and gross motor scores appeared stable, but fine motor and receptive communication scores decreased. The median CGI-I score was 3 (indicating minimal improvement) at 2 years and 4 (indicating no change) at 3 years; in historical controls, scores have been shown to increase (indicating worsening) over time. Neuroimaging showed patterns consistent with reduced rates of cerebral atrophy and favorable changes in myelination as compared with baseline.

Conclusions: In this study involving nine participants with type II GM1 gangliosidosis, a single infusion of AAV9 encoding β-galactosidase was associated with adverse events, including severe vomiting in one participant and elevated liver-enzyme levels in all participants. Secondary end-point results suggested improvements in biochemical markers and neuroimaging patterns and stable or reduced rates of developmental deterioration in some measures.

Grieving parents of a 26-year-old man against Canada’s medical assistance in dying laws

Mother sounds alarm on social media addiction after losing teen son to suicide

Maurine Molak shares her story after her 16-year-old son, David, died by suicide in 2016 and argues safeguards 'don't work' as tech giants face trial over the alleged addictive and harmful nature of social media platforms.

The grieving parents of a 26-year-old man are speaking out against Canada’s medical assistance in dying (MAID) laws, arguing the system failed to protect their "vulnerable" son from being euthanized, despite a history of mental illness.

Kiano Vafaeian was euthanized on Dec. 30, 2025, in British Columbia. His family says he was diagnosed with Type 1 diabetes at age 4 and began struggling with mental health after a car accident at 17. 

His mother, Margaret Marsilla of Ontario, said his depression was often seasonal, yet he became "obsessed" with MAID after losing vision in one eye in 2022.

"He kept on emphasizing about how he could get approved," Marsilla told Fox News Digital. "We never thought there would be a chance that any doctor would approve a 22- or 23-year-old at that time for MAID because of diabetes or blindness."

MAID was legalized in Canada in June 2016. The law allows patients with "grievous and irremediable" medical conditions to request a lethal drug that is either physician or self-administered, to end their lives.

In 2022, after a Toronto doctor initially approved Vafaeian’s request, the family launched a public pressure campaign on social media to voice their opposition. The outcry led the doctor to withdraw approval. While Vafaeian was initially angry, his family said he showed signs of improvement over the following year, even moving in with them in 2024.

"He tried his best when he was in one of those good highs of life," Marsilla said. "Then winter, fall started coming around, he started changing and then everything that we had worked for from spring and summertime just disappeared… he would start talking about MAID again."

The family said Vafaeian was rejected by multiple doctors in Ontario before he sought out Dr. Ellen Wiebe, a prominent MAID provider, in British Columbia. Marsilla believes Wiebe "coached" her son on what to say to meet the criteria for "Track 2" patients — those whose natural deaths are not reasonably imminent.

"We believe that she was coaching him... on how to deteriorate his body and what she can possibly approve him for and what she can get away with approving him for," Marsilla said. "Because if he had spoken back in 2024, and he was a good candidate for approving MAID, she would have done it right away, but she didn't."

Vafaeian’s parents say they were not notified of the approval and only learned of his death days after it occurred. They noted his medical records did not substantiate the "severe peripheral neuropathy" listed on his death certificate as a qualifying factor.

"This whole process came to us as a shock," said Joseph Caprara, Vafaeian’s stepfather.

In 2021, eligibility for MAID was expanded to include applicants with "grievous and irremediable conditions" whose deaths are not reasonably foreseeable. The family is now advocating for the repeal of this "Track 2" provision and the passage of Bill C-218, a legislative effort to restrict MAID for patients whose underlying issue is solely mental illness.

"Realistically, safeguards for patients would be reaching out to their family members, giving them a whole bunch of different treatment options," Marsilla said. Instead, she claims the current system allows doctors to approve and euthanize patients within 90 days on Track 2. 

"How is that safe for patients?" she asked.

Marsilla has shared her son's story on social media, describing the situation as "disgusting on every level."

On Facebook, she wrote, "No parent should ever have to bury their child because a system—and a doctor—chose death over care, help, or love."

Caprara said their family hopes sharing their story will expose the risks these laws pose to the "vulnerable and disabled" and give states and other countries pause before implementing similar legislation.

"We don't want to see any other family member suffer, or any country introduce a piece of legislation that kills their disabled or vulnerable without appropriate proper treatment plans that could save their lives," he said.

In a statement to Fox News Digital, Dr. Wiebe said, "Like my colleagues, every patient I approve for Track 2 has unbearable suffering from a grievous and irremediable medical condition (not psychiatric) with an advanced state of decline in capability and consents to MAID fully informed about treatments to reduce the suffering."

New York Gov. Kathy Hochul signed an assisted suicide bill into law on Monday, making New York the 13th state, plus the District of Columbia, to legalize allowing physicians to aid terminally ill adults in dying by suicide. The law will go into effect in six months.

Kristine Parks 

https://www.foxnews.com/media/grieving-parents-demand-changes-after-26-year-old-son-euthanized-under-controversial-law

Truncating variants of TRIM8 and atypical neuro-renal syndrome:

Inspired by a colleague's patient

Weng PL, Majmundar AJ, Khan K, Lim TY, Shril S, Jin G, Musgrove J, Wang M, Ahram DF, Aggarwal VS, Bier LE, Heinzen EL, Onuchic-Whitford AC, Mann N, Buerger F, Schneider R, Deutsch K, Kitzler TM, Klämbt V, Kolb A, Mao Y, Moufawad El Achkar C, Mitrotti A, Martino J, Beck BB, Altmüller J, Benz MR, Yano S, Mikati MA, Gunduz T, Cope H, Shashi V; Undiagnosed Diseases Network; Trachtman H, Bodria M, Caridi G, Pisani I, Fiaccadori E, AbuMaziad AS, Martinez-Agosto JA, Yadin O, Zuckerman J, Kim A; UCLA Clinical Genomics Center; John-Kroegel U, Tyndall AV, Parboosingh JS, Innes AM, Bierzynska A, Koziell AB, Muorah M, Saleem MA, Hoefele J, Riedhammer KM, Gharavi AG, Jobanputra V, Pierce-Hoffman E, Seaby EG, O'Donnell-Luria A, Rehm HL, Mane S, D'Agati VD, Pollak MR, Ghiggeri GM, Lifton RP, Goldstein DB, Davis EE, Hildebrandt F, Sanna-Cherchi S. De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis. Am J Hum Genet. 2021 Feb 4;108(2):357-367. doi: 10.1016/j.ajhg.2021.01.008. Epub 2021 Jan 27. PMID: 33508234; PMCID: PMC7895901.

Abstract

Focal segmental glomerulosclerosis (FSGS) is the main pathology underlying steroid-resistant nephrotic syndrome (SRNS) and a leading cause of chronic kidney disease. Monogenic forms of pediatric SRNS are predominantly caused by recessive mutations, while the contribution of de novo variants (DNVs) to this trait is poorly understood. Using exome sequencing (ES) in a proband with FSGS/SRNS, developmental delay, and epilepsy, we discovered a nonsense DNV in TRIM8, which encodes the E3 ubiquitin ligase tripartite motif containing 8. To establish whether TRIM8 variants represent a cause of FSGS, we aggregated exome/genome-sequencing data for 2,501 pediatric FSGS/SRNS-affected individuals and 48,556 control subjects, detecting eight heterozygous TRIM8 truncating variants in affected subjects but none in control subjects (p = 3.28 × 10-11). In all six cases with available parental DNA, we demonstrated de novo inheritance (p = 2.21 × 10-15). Reverse phenotyping revealed neurodevelopmental disease in all eight families. We next analyzed ES from 9,067 individuals with epilepsy, yielding three additional families with truncating TRIM8 variants. Clinical review revealed FSGS in all. All TRIM8 variants cause protein truncation clustering within the last exon between residues 390 and 487 of the 551 amino acid protein, indicating a correlation between this syndrome and loss of the TRIM8 C-terminal region. Wild-type TRIM8 overexpressed in immortalized human podocytes and neuronal cells localized to nuclear bodies, while constructs harboring patient-specific variants mislocalized diffusely to the nucleoplasm. Co-localization studies demonstrated that Gemini and Cajal bodies frequently abut a TRIM8 nuclear body. Truncating TRIM8 DNVs cause a neuro-renal syndrome via aberrant TRIM8 localization, implicating nuclear bodies in FSGS and developmental brain disease.

Sakai Y, Fukai R, Matsushita Y, Miyake N, Saitsu H, Akamine S, Torio M, Sasazuki M, Ishizaki Y, Sanefuji M, Torisu H, Shaw CA, Matsumoto N, Hara T. De Novo Truncating Mutation of TRIM8 Causes Early-Onset Epileptic Encephalopathy. Ann Hum Genet. 2016 Jul;80(4):235-40. doi: 10.1111/ahg.12157. PMID: 27346735.

Abstract

Background: Early-onset epileptic encephalopathy (EOEE) is a heterogeneous group of neurodevelopmental disorders characterised by infantile-onset intractable epilepsy and unfavourable developmental outcomes. Hundreds of mutations have been reported to cause EOEE; however, little is known about the clinical features of individuals with rare variants.

Case report and methods: We present a 10-year-old boy with severe developmental delay. He started experiencing recurrent focal seizures at 2 months old. Serial electroencephalograms persistently detected epileptiform discharges from the left hemisphere. Whole-exome sequencing and array-comparative genome hybridization were performed to search for de novo variations. Two-week-old C57Bl/6 mice were used for immunofluorescence studies.

Results: This case had a paternally inherited, 0.2-Mb duplication at chromosome 22q11.22. The whole-exome sequencing identified a de novo truncating mutation of tripartite motif containing 8 (TRIM8) (NM_030912:c.1099_1100insG:p.C367fs), one of the epileptic encephalopathy-associated genes. We verified that the murine homologues of these genes are expressed in the postnatal mouse brain.

Conclusion: This is the second case of EOEE caused by a de novo truncating mutation of TRIM8. Further studies are required to determine the functional roles of TRIM8 in the postnatal development of the human brain and its functional relationships with other EOEE-associated genes.

Li W, Guo H. De novo truncating variants of TRIM8 and atypical neuro-renal syndrome: a case report and literature review. Ital J Pediatr. 2023 Apr 15;49(1):46. doi: 10.1186/s13052-023-01453-4. PMID: 37061734; PMCID: PMC10105407.

Abstract

Background: The TRIM8 gene encodes a protein that participates in various biological processes. TRIM8 variants can lead to early termination of protein translation, which can cause a rare disease called neuro-renal syndrome. This syndrome is characterized by epilepsy, psychomotor retardation, and focal segmental glomerulosclerosis. However, we found that some patients may not present the above typical triad, and the reason may be related to their variant sites.

Case presentation: We report a case of a 6-year-old boy with nephrotic-range proteinuria as the first prominent manifestation of TRIM8 variant. He had stage 3 chronic kidney disease at the time of presentation, specific facial features, and a neurogenic bladder. He had not experienced seizures previously. There were no apparent abnormalities in his growth, intelligence, or motor development. The results of whole exome sequencing showed a TRIM8 variant. Renal biopsy revealed focal segmental glomerulosclerosis and renal tubular cystic dilatation. He did not respond to hormone and angiotensin-converting enzyme inhibitor treatment; however, the symptoms of neurogenic bladder were relieved after treatment with Solifenacin.

Conclusion: In this case, renal disease was the prominent manifestation; the patient had no other obvious neurological symptoms except a neurogenic bladder. Notably, the variant site is the closest to the C-terminal to date. Based on the analysis of previously reported cases, we found that as the TRIM8 variant became closer to the C-terminal, the renal lesions became more prominent, and there were fewer neurologic lesions. Our findings provide a new understanding of neuro-renal syndrome caused by TRIM8 variant. Patients may only have kidney disease as a prominent manifestation. At the same time, we found that we should also pay attention to the eye lesions of these patients. Therefore, gene analysis is helpful in identifying the etiology and guiding the prognosis of patients with hormone-resistant proteinuria. We suggest that TRIM8 should be included in gene panels designed for the genetic evaluation of hormone-resistant proteinuria.