Oligodendroglioma

Busy Philipps is “grateful to be alive” after a shocking health scare.

The 47-year-old actress revealed this week that doctors discovered a rare, slow-growing malignant tumor in her brain earlier this year, despite her having no obvious symptoms.

Philipps opened up about the ordeal in a People cover story published Wednesday, saying she underwent two surgeries as a result of her grade 2 oligodendroglioma.

The “Dawson’s Creek” alum called the past six months the “weirdest” of her life, dubbing herself “the luckiest girl in the world” after following through with a full-body MRI scan her primary physician had initially talked her out of.

She ultimately decided to schedule the scan after speaking with her cousin-in-law, Dr. Justin Donlan, an internist who told her that “knowledge is power.”

Doctors spotted the tumor during a Prenuvo scan on Feb. 12, just one day after her former co-star James Van Der Beek died of colorectal cancer at age 48. The star had actually been considering canceling her appointment when her husband suggested the health check might be “the best thing” she could do for her late friend.

So, what exactly is an oligodendroglioma — and what subtle symptoms can signal the disease? Here’s what to know.

What are oligodendrogliomas?

An oligodendroglioma is a rare type of brain tumor that can also develop in the spinal cord. It starts in oligodendrocytes, cells that help support and protect the nerve cells responsible for sending messages throughout the brain and nervous system, according to the Cleveland Clinic.

Philipps was diagnosed with a grade 2 oligodendroglioma, which is considered a “low-grade” tumor by the World Health Organization. That means it typically grows slowly and is generally easier to treat than more aggressive brain tumors.

“It is considered malignant, but it has the best prognosis of all of the malignant gliomas,” Dr. Alexandra Miller, Philipps’ neuro-oncologist at NYU Langone, told People.

“It’s sort of defined as a cancerous tumor based on the ability of the tumor to regrow over time, rather than it looking very malignant under the microscope.”

Higher-grade oligodendrogliomas are more aggressive. As they become more advanced, the tumors can grow faster, damage surrounding brain tissue and become more difficult to treat.

How common is oligodendrogliomas?

Oligodendrogliomas are relatively rare, accounting for an estimated 1.3% of all brain tumors in the US. About 1,100 Americans are diagnosed with the tumor each year, according to the American Brain Tumor Association.

They are most often diagnosed in adults between the ages of 20 and 40. The tumors are considered extremely rare in children under 15.

What are the symptoms of oligodendrogliomas?

Oligodendrogliomas can cause different symptoms depending on where the tumor is located and how big it grows. The most common warning sign is a seizure, which affects nearly 80% of patients, according to Columbia University.

When a tumor develops in the frontal lobe, it can trigger personality or behavior changes, as well as weakness or partial paralysis on one side of the body, known as hemiparesis.

Other symptoms can include headaches, partial vision loss and trouble with speech or language. Tumors in the temporal lobe, however, can be especially sneaky, sometimes causing few noticeable symptoms and going undetected for years.

Philipps said doctors caught her tumor before she developed any obvious symptoms. Still, in the years before her diagnosis, she had told her former “Dawson’s Creek” co-star and close friend Michelle Williams that she felt like her brain was “broken.”

“I’ve been saying this for the last few years,” Philipps told People. “I wasn’t consciously aware that anything was really wrong, but there was something that was misfiring. Like, I could not get a handle on it.”

How are oligodendrogliomas treated?

Oligodendrogliomas are considered one of the more treatable types of brain cancer.

Surgery is usually the first line of attack, with doctors aiming to remove as much of the tumor as possible without damaging healthy brain tissue. Depending on the results, patients may also need radiation or chemotherapy.

For Philipps, that meant a roughly five-hour surgery on March 2 to remove the 2.6-centimeter mass from her brain. Doctors identified it as an oligodendroglioma after biopsying the tumor.

Her doctors told her that waiting until she developed seizures could have allowed the tumor to grow to two or three times its size — potentially making it more difficult to remove completely.

Philipps initially made it through the operation without incident, but later developed a staphylococcus infection in her incision. She needed a second surgery to clean out the infected area and remove one of the tiny titanium tacks doctors had used to hold her skull bone in place.

Are oligodendrogliomas deadly?

Many patients have a good chance of living for years after diagnosis.

The outlook is typically better when the tumor is caught early. Between 69% and 90% of people with low-grade oligodendrogliomas are still alive five years after diagnosis, according to the Cleveland Clinic, with survival rates potentially even higher among younger adults.

For people with high-grade oligodendrogliomas, the five-year survival rate ranges from 45% to 76%.

Philipps told People she feels grateful for going through with the Prenuvo scan that caught her tumor, saying she hopes she can inspire other people to listen to their gut.

“We are frequently told by doctors that there is nothing to worry about [when] you kind of know that there’s something to worry about,” she said. “There’s nothing to be afraid of in having information. It’s only empowering.” 

McKenzie Beard

https://nypost.com/health/what-is-oligodendroglioma/

Epiwatch for tonic-clonic seizure detection in children and adults

Krauss GL, Elizebath R, Shah S, et al. Phase III trial of epiwatch for tonic-clonic seizure detection in children and adults https://www.neurology.org/doi/10.1212/WN9.0000000000000111. Neurol Open Access. 2026; Epub 2026 May 27.

Abstract

Background and Objectives

Risks of sudden unexpected death in epilepsy are high in individuals with uncontrolled tonic-clonic seizures (TCSs), particularly in those who sleep alone. Wearable seizure detection devices can alert caregivers to provide timely intervention; however, current devices risk stigma and have high false alarm rates (FARs) that discourage consistent use and caregiver responses. EpiWatch is a seizure detection application (app) developed for the Apple Watch, designed to minimize FAR without compromising detection sensitivity or latency. We evaluated the sensitivity and FAR of EpiWatch for detecting TCSs in children and adults undergoing video-EEG monitoring.

Methods

We conducted a prospective, multicenter Phase III diagnostic accuracy study at 6 epilepsy monitoring units (EMUs) from September 2021 to October 2023. Children and adults aged 5 years and older with a history of TCSs or clinical potential for TCSs and who underwent video-EEG monitoring were eligible. Participants wore the EpiWatch device on the wrist contralateral to their seizure focus. EpiWatch detections were compared with TCS events classified by an independent Central Reader Panel of epileptologists blinded to device output. Co-primary end points were sensitivity and FAR per 24 hours. Secondary end points included detection latency and performance during sleep. Enrollment was slowed during COVID-19 restrictions, which extended the recruitment period.

Results

A total of 242 participants were enrolled (mean age 22.7 years; 54.1% female; 60.7% aged 5–21). EpiWatch detected 46 of 47 panel-verified TCSs; 1 seizure was missed when a caregiver restrained the participant's arm. The overall sensitivity was 98% (95% CI 95%–100%). There were 56 false alarms during 16,189 hours of monitoring, with a FAR of 0.08 per 24 hours (95% CI 0.02–0.12), equivalent to 1 false alarm every 12.4 days. All age groups had similarly low FARs. The median detection latency was 31.5 seconds. During sleep, all TCSs were detected, and all false alarms from sleep were associated with seizure activity. No adverse events occurred.

Discussion

EpiWatch detected TCSs with high sensitivity and a FAR approximately one-tenth that of other published devices. These findings were obtained in a controlled EMU environment; real-world performance may differ.

Classification of Evidence
This study provides Class I evidence that, in patients with a history of TCSs, the EpiWatch accurately detects TCSs, with a low FAR. EPW001.

Cerebellitis

When your child gets a cold, you expect they’ll probably have a runny nose, cough and maybe sneeze sometimes. You don’t expect to find them in bed one morning limp and unresponsive. Unfortunately, that’s how Britta and Ross found their then 2-year-old daughter Sydney in November 2024.

Symptoms and diagnosis of rare brain condition

Sydney had been showing signs of a slight cold for about a week. But when Britta went to check on her that morning in November, she knew something was wrong the moment she turned on the lights.

“She didn’t sit up. She was very lethargic. It was clear she was very sick,” she described.

The family rushed her to urgent care. The staff quickly called an ambulance to take Sydney to the Children’s Minnesota hospital in Minneapolis. When they arrived, the care team ran a series of tests, including a CT scan, an MRI, a spinal tap and an

Results showed she had a very rare case of cerebellitis, which is an inflammatory condition that affects the cerebellum, a part of the brain responsible for coordination and balance. That’s why she wasn’t moving or responding. The care team suspected it was caused by a combination of common cold viruses in her body at the same time and her brain just reacted.

Britta and Ross remembered the care team telling them the odds of this happening to their daughter were, “probably one in a million.”

As a result of the cerebellitis, Sydney’s cerebellum swelled, blocking the flow of fluid in her brain. As the fluid built up, it put pressure on her brain, a condition known as hydrocephalus.

Emergency brain surgery

Sydney’s condition was serious. She was moved to the pediatric intensive care unit (PICU) so she could be closely monitored. The hope was the brain swelling would eventually peak and begin to go down over five days. But on the fifth day, in the middle of the night, her breathing stopped. The care team rushed in, put in a breathing tube and told the family she needed emergency brain surgery.

During the emergency surgery, Kyle Halvorson, MD, pediatric neurosurgeon at Children’s Minnesota, put a device in Sydney’s skull to help drain the fluid that was building up. He also did a procedure to relieve pressure on the cerebellum and spinal cord.

“The first thing Dr. Halvorson told us after surgery was, ‘Everything went as planned.’ I began crying and hugging him. So many people saved her life,” said Britta.

And after being up all night, Britta and Ross fell asleep for a couple hours. They were woken up by the care team. Sydney needed another brain surgery.

“I just felt like my heart had been shattered and put back together so many times during all this,” Britta described. “You just keep digging for strength.”

Second brain surgery then slow recovery

The neurosurgery team explained that Sydney needed more invasive brain surgery because there was still a lot of fluid and swelling in her brain. The second brain surgery was with Meysam Kebriaei, MD, medical director of neurosurgery at Children’s Minnesota. During the second brain surgery, the drain in Sydney’s skull was adjusted to better release the extra fluid. The protective covering of her brain was also opened, and a small part of her cerebellum was removed.

After the second brain surgery, everything suggested Sydney had a great chance to get back to being the bubbly little girl her family loved. However, her road to get there was going to be slow.

Sydney spent the next four weeks in the PICU. Day by day she slowly got better. Her eye movements became more natural. After a week she gave a big smile. Eventually she was responding to requests to move her fingers and toes.

“This condition is incredibly rare, and not all patients survive,” said Dr. Kebriaei. “Our neurosurgery team, along with the teams from PICU, neurology, infectious disease, rehabilitation and so many others, joined together to do everything we knew how to care for Sydney and get her on the path to recovery. She is a very resilient girl.”

Rehabilitation for the effects of cerebellitis

While Sydney was getting better, the cerebellitis left her with significant challenges. She lost so much muscle tone she couldn’t hold her head up. She didn’t know how to swallow, had speech issues and needed help doing almost anything. The team at Children’s Minnesota recommended she go to the inpatient rehabilitation program at Gillette Children’s.

In mid-December, Sydney moved to Gillette Children’s where she received about two months of rehabilitation including daily physical therapy (PT), occupational therapy (OT), and speech therapy. She continues her PT and OT as an outpatient at the Children’s Minnesota rehabilitation clinic in Minnetonka. Her progress has been impressive. She’s once again walking, talking, running and trying to keep up with her two big sisters.

A family's gratitude

As Sydney continues to recover, the family is thankful for the team of experts who cared for her every step of the way.

“Truly how incredibly talented and collaborative the team was at Children’s [Minnesota] and how they worked together to come up with her next steps. It consistently exceeded our expectations,” said Britta. “That was the one thing that struck us the most was all of the different areas of deep expertise and how they really came together.”

Sydney with her parents and sisters

Nick Petersen

https://www.childrensmn.org/blog/sydneys-incredible-recovery-from-rare-brain-condition-likely-caused-by-common-cold-viruses/

Baby Gabriel

The surrogate who refused to have an abortion despite the wishes of the baby’s biological parents vowed Thursday to take the legal fight all the way to the Supreme Court — with her lawyer declaring, “She is the mother.”

Lincoln Wilson, an attorney for surrogate McKenna West, told The Post she’s planning a full-throttle court battle to become the legal parent of baby “Gabriel,” who was born in the Dallas area Wednesday.

“She is seeking parentage of the child because she gave birth in Texas, and in Texas, if you give birth to a child, it’s your child,” Wilson said.

Wilson said the reason the baby’s LA-based biological parents, Nausheen Gilkar and Omar Ahmed, currently have custody is because of a California order he considers “void.”

“We think that once that California judgment is removed … that basically she is the mother under Texas law,” Wilson said.

“We are taking that challenge up through the California courts, and we’ll take it up to the US Supreme Court if we have to.”

The biological parents had asked that their unborn child be aborted after he was diagnosed with a severe but treatable heart condition earlier this year.

The surrogacy contract between West, a nurse from Alaska, and the biological parents contained a clause that allowed terminations if there was an “anomaly” during the pregnancy.

But after the couple asked West to abort the fetus, she refused and instead traveled to Texas, where she would be recognized as the birth mother under state law.

Wilson said Thursday surrogacy contracts like the one in West’s case are common — but likened them to a “hitman contract.”

“These forced abortion clauses that demand that women have to be required to abort a child at the late term are quite common in surrogacy contracts,” he said.

“There’s some contracts the law doesn’t enforce. Like the law doesn’t enforce a hitman contract,” he said.

“This is basically a hitman contract, and we think that even if you accept a liberal view of abortion rights, the right to get an abortion also entails the right to not get an abortion.”

West currently has no legal authority over the baby to whom she gave birth, under a temporary restraining order filed by the couple.

The restraining order reportedly strips her of any decision-making about the infant’s care, including on medical decisions, and bars her from representing herself as a parent.

Wilson said the baby will soon undergo a series of heart surgeries at a hospital with an excellent track record.

“Within a few days, the first of three surgeries will be performed. It’s called the Norwood procedure,” Wilson said.

“But thankfully, we are at a hospital that has a 100% success rate in giving that procedure, so we know that she and well, at this point, baby Gabriel are in good hands.”

The fierce legal battle first began in April after the unborn child was diagnosed with the severe heart condition, hypoplastic left heart syndrome, at 20 weeks.

West, who named the baby Gabriel, was not allowed to see or hold the baby due to the court order.

Ahmed and Gilkar have reportedly picked a different name for the boy.

Kyra Breslin and Natalie O'Neill

https://nypost.com/2026/08/13/us-news/surrogate-mckenna-west-vows-legal-fight-against-bio-parents-she-is-the-mother/

Brain death determination controversy

Courtesy of my son

Annelise Camp, a 2-year-old girl whose parents sued to stop Texas Children’s Hospital from testing if she’s brain dead, died Monday after her breathing tube was removed.

In social media posts, Annelise’s family confirmed her death, ending a months-long legal dispute over whether hospitals need a family’s consent to test a patient for brain death. The New York Times first reported her death.

“Annelise is now with Jesus,” wrote her parents, Johnston Camp and Joy Camp, on the family’s GoFundMe page. “We pray that her legacy continues to inspire compassion, encourage meaningful change, and bring hope to families for years to come.”

                                   https://www.instagram.com/p/Dby1T05HxBT/

Rep. Steve Toth, R-The Woodlands, who has been in contact with Annelise’s father, said the family just told Annelise’s two siblings of her death.

“It’s been traumatic for the family,” said Toth in an interview with the Texas Tribune.

The Camps’ lawsuit, filed at the end of May, was part of a larger debate supported by anti-abortion advocates that challenged the use of brain death testing. The Camps had hoped that by preventing brain death testing and a determination of whether their daughter was brain dead, hospitals would be forced to keep Annelise on life-supporting services for as long as possible.

Under Texas law, brain death is the irreversible cessation of all brain function and hospitals are not required to obtain family consent before conducting the tests. Once a patient is declared brain dead, hospitals can withdraw life sustaining measures.

It is unclear why Annelise was extubated. According to a Facebook post from Steven Camp, her grandfather, Annelise passed shortly after the breathing tube was removed. The Camp family has not responded to requests for comment.

The family said in court filings that the testing conflicted with their religious beliefs. Texas Right to Life, who worked with the family, argued that a patient is alive as long as their heart is beating, even when breathing is sustained by a ventilator.

On Memorial Day, Annelise was pulled from a hotel swimming pool and taken to Texas Children’s Hospital, where she was placed on a ventilator. After three days, doctors said they had exhausted treatment options and recommended evaluating her for brain death to which her parents began legal action to block testing.

Annelise was transferred from Texas Children’s Hospital in Houston to Ochsner Medical Center in New Orleans, but was transferred back to a Texas hospital, Christus Mother Frances Hospital in Tyler, about a week ago, Toth said.

Toth hopes Annelise’s story will influence change by giving families in Texas and across the country more time on life-support services.

“Life is fragile, it shouldn’t be disposable,” Toth said.

Disclosure: Texas Children’s Hospital and The New York Times have been financial supporters of The Texas Tribune, a nonprofit, nonpartisan news organization that is funded in part by donations from members, foundations and corporate sponsors. Financial supporters play no role in The Texas Tribune’s journalism. Find a complete list of them here.

Katlyn Ma

https://www.texastribune.org/2026/08/07/texas-brain-death-testing-annelise-camp/

What happens when medical students rely on AI

Courtesy of my son

What happens when medical students rely on AI – and never develop their own judgment?

AI’s danger isn’t just in experts losing the ability to reason. It’s that trainees may never learn how to do so in the first place

In healthcare, there’s growing concern over doctors becoming less clinically adept as they increasingly rely on AI tools. But what about the trainees – medical students, residents and fellows – who are using these tools before they have built their own clinical judgment? The idea of deskilling implies that someone possessed an ability and then lost it. Here, the danger is not just deskilling but never-skilling. Although a doctor who has forgotten how to reason is recoverable, one who never learned how may not be.

OpenEvidence, essentially an AI chatbot for clinicians, has given this concern its most concrete form. About two-thirds of US doctors actively use OpenEvidence, asking about puzzling symptoms, drug interactions and clinical guidelines, getting responses within seconds, anchored in the latest research. Trainees, unsurprisingly, have also begun to use this AI tool in many of the same ways – but at a far more formative stage.

For example, trainees once asked to build a list of potential diagnoses might struggle and offer an incomplete set, learning what they missed, sometimes painfully. Now, trainees can simply ask OpenEvidence and get a nearly perfect answer, complete with possibilities they might have never considered and none of the embarrassment of having overlooked them. Repeating this answer on the wards may make the trainee look prepared and even impress the supervising doctor.

However, this performance can also conceal the very deficit that training is meant to reveal: that the struggle is the point. Medical training, more than most professions, is an apprenticeship. A student becomes a resident, a resident becomes a fellow, and a fellow becomes an attending – every step shaped by failure, uncertainty and increasing responsibility. With years of repetition and watchful supervision, the habits of clinical reasoning slowly become part of the physician’s inner architecture.

Technology has long shifted how people learn medicine, from advanced imaging to electronic medical records. But AI is different, not just expanding what doctors can see but inserting itself into the cognitive machinery that training is meant to build. As these tools become more capable and the physician’s role increasingly involves supervising them, experienced clinicians may have enough intuition and independent judgment to critically evaluate the machine’s answers. But for trainees whose understanding of medicine is being formed alongside AI, the relationship is more fraught. Can they really question the reasoning that shaped their own? What happens when the generation trained by AI becomes the generation responsible for catching its mistakes? With unchecked use among trainees, we risk creating supervisors of reasoning before we create reasoners.

The stakes of that question are growing: a recent study in Nature Medicine found that tools pulling from the latest medical literature, like OpenEvidence does, can be less reliable than they appear and, in some cases, less accurate than general-purpose AI chatbots. The problem of misplaced trust is already embedded in the AI that trainees are using today.

To be clear, many trainees sense the trap, telling us they know that tools such as OpenEvidence can become a crutch. But these trainees also feel stuck in an arms race: if everyone else is using AI to sound more prepared, opting out feels like unilateral disarmament. The solution, then, cannot rest on individual restraint. It has to be structural.

That is why medical schools and residency programs need to shape not just whether trainees use AI, but when. No one can police every search on every phone, nor should they. But supervising doctors can build a simple expectation – reason first, consult AI second – and assess accordingly. Trainees should have to make their unaided first pass visible, committing to a leading diagnosis, naming the dangerous possibilities to rule out, and explaining what to do next. In practice, that might mean a resident who admits a patient overnight first writes a brief “pre-AI assessment” after the history and physical exam. On rounds, when a new lab result or symptom changes the case, the attending might need to pause the team – before anyone can consult AI – to ask how this changes the diagnosis or treatment plan.

As AI becomes more deeply integrated into medicine, this will feel cumbersome and inefficient. But such friction is purposeful: the learning scientists Elizabeth and Robert Bjork describe how “desirable difficulties” slow performance in the moment but improve retention and transfer of skills over time. In fact, used after an independent attempt, AI could actually serve as a powerful tutor, showing trainees what they missed and what they overemphasized.

Sequencing, however, may not be enough on its own. Aviation thus offers a useful precedent: pilots in training are not taught to avoid autopilot but to preserve their manual competence. The Federal Aviation Administration even advises pilots to maintain manual flying skills by periodically disengaging automation and hand-flying. Medicine needs similar discipline, with trainees required to periodically work through no-AI cases and assessed on their unaided reasoning to reveal potential drift.

Finally, trainees should be taught to interrogate AI itself. Programs could run the medical equivalent of flight simulator drills, built from real clinical cases: for example, a polished AI-generated assessment with a subtle flaw. Afterward, attendings could debrief not only whether the trainee reached the right answer but also when they trusted the tool, when they questioned it, and when they found the flaw. Just as important, attendings should mix in AI outputs that are perfectly accurate, so students learn not reflexive skepticism but disciplined judgment.

None of this is an argument for making medical training harder for its own sake or romanticizing humiliation as pedagogy. In every generation of medicine, there is a temptation to confuse difficulty with virtue, but the struggle to independently reason through a patient’s case is not hazing but a core competency.

AI is here to stay, and patients stand to benefit from its speed and reach. But patients will also need doctors who can stand apart from the machine long enough to know when it is wrong, incomplete, or right for the wrong reason – doctors whose reasoning is not subordinated to it. Although AI can reason over the facts it is given, a trainee who has seen pneumonia that looks like pneumonia, then pneumonia that looks like heart failure, then heart failure that looks like pneumonia, develops a richer bedside judgment: what to notice, what to question, and when a familiar pattern should be distrusted. That is what medical training is trying to produce. AI should help augment this, not replace it.

Simar Bajaj and Joseph Sakran

Simar Bajaj is a medical student and Knight-Hennessy Scholar at Stanford University School of Medicine, as well as an award-winning journalist

Dr Joseph V Sakran is a trauma surgeon and public health expert who serves as executive vice-chair of surgery at Johns Hopkins Medicine

https://www.theguardian.com/commentisfree/2026/aug/10/ai-medical-students-judgment

Xia-Gibbs syndrome

Inspired by a patient

Shirai H, Oitani Y, Nishi E, Haraguchi K, Nakamura T, Ichinose F, Sanefuji M, Hattori A, Yanagi K, Shimojima Yamamoto K, Okamoto N, Matsuo M, Saitoh S, Yoshiura KI, Kaname T, Yamamoto T. Clinical and molecular profiles of patients with Xia-Gibbs syndrome: a cohort in Japan. Brain Dev. 2026 Apr;48(2):104509. doi: 10.1016/j.braindev.2026.104509. Epub 2026 Feb 6. PMID: 41653504.

Abstract

Background: Xia-Gibbs syndrome (XGS) is a rare neurodevelopmental disorder caused by pathogenic variants in the AT-hook DNA binding motif containing 1 (AHDC1) gene. More than 100 patients with XGS have been reported. In this study, we describe the findings from a Japanese cohort of patients with XGS. To enhance understanding, we also conducted a systematic literature review of XGS.

Methods: We collected clinical and genetic information from seven new Japanese patients with XGS which were diagnosed through comprehensive genetic analysis. A systematic literature review was also conducted using PubMed.

Results: All Japanese patients carried premature truncation variants or deletions. The core clinical features were global developmental delay and hypotonia, which were consistent with those observed in the 106 previously reported patients identified in our literature review. In one patient with a frameshift variant, escape from nonsense-mediated mRNA decay was confirmed using the patient's sample.

Conclusion: The clinical and molecular profiles of Japanese patients with XGS were analyzed and compared with those of previously reported patients from other countries, confirming the consistent characteristics of XGS. This study provides direct evidence of nonsense-mediated mRNA decay escape. A comprehensive understanding of this expanding phenotype is crucial for accurate diagnosis and management.

Jiang N, Zhang L, Zheng Z, Du H, Chen S, Pan H. Phenotypic subtypes of Xia-Gibbs syndrome: a latent class analysis. Eur J Hum Genet. 2025 Dec;33(12):1558-1566. doi: 10.1038/s41431-024-01754-0. Epub 2024 Dec 9. Erratum in: Eur J Hum Genet. 2026 Jun;34(6):886-892. doi: 10.1038/s41431-025-01825-w. PMID: 39648204; PMCID: PMC12669642.

Abstract

Xia-Gibbs syndrome (XGS) is a rare neurodevelopmental disorder with considerable clinical heterogeneity. To further characterize the syndrome's heterogeneity, we applied latent class analysis (LCA) on reported cases to identify phenotypic subtypes. By searching PubMed, Embase, China National Knowledge Infrastructure and Wanfang databases from inception to February 2024, we enrolled 97 cases with nonsense, frameshift or missense variants in the AHDC1 gene. LCA was based on the following 6 phenotypes with moderate occurrence and low missingness: ataxia, seizure, autism, sleep apnea, short stature and scoliosis. After excluding cases with missing data on all LCA variables or with unmatched phenotype-genotype information, a total of 85 cases were selected for LCA. Models with 1-5 classes were compared based on Akaike Information Criterion, Bayesian Information Criterion, Sample-Size Adjusted BIC and entropy. We used multinomial logistic regression (MLR) analyses to investigate the phenotype-genotype association and potential predictors for class membership. LCA revealed 3 distinct classes labeled as Ataxia subtype (n = 11 [12.9%]), Sleep apnea & short stature subtype (n = 23 [27.1%]) and Neuropsychological subtype (n = 51 [60.0%]). The commonest Neuropsychological subtype was characterized by high estimated probabilities of seizure, ataxia and autism. By adjusting for sex, age and variant type, MLR showed no significant association between phenotypic subtype and variant position. Age and variant type were identified as predictors of class membership. The findings of this review offer novel insights for different presentations of XGS. It is possible to deliver targeted monitoring and treatment for each subtype in the early stage.

Romano F, Falco M, Cappuccio G, Brunetti-Pierri N, Lonardo F, Torella A, Digilio MC, Dentici ML, Alfieri P, Agolini E, Novelli A, Garavelli L, Accogli A; TUDP; Striano P, Scarano G, Nigro V, Scala M, Capra V. Genotype-phenotype spectrum and correlations in Xia-Gibbs syndrome: Report of five novel cases and literature review. Birth Defects Res. 2022 Aug 1;114(13):759-767. doi: 10.1002/bdr2.2058. Epub 2022 Jun 18. PMID: 35716097; PMCID: PMC9545659.

Abstract

Background: Xia-Gibbs syndrome (XGS) is a rare neurodevelopmental disorder caused by pathogenic variants in the AT-hook DNA-binding motif-containing 1 gene (AHDC1), encoding a protein with a crucial role in transcription and epigenetic regulation, axonogenesis, brain function, and neurodevelopment. AHDC1 variants possibly act through a dominant-negative mechanism and may interfere with DNA repair processes, leading to genome instability and impaired DNA translesion repair. Variants affecting residues closer to the N-terminal are thought to determine a milder phenotype with better cognitive performances. However, clean-cut genotype-phenotype correlations are still lacking.

Cases: In this study, we investigated five subjects with XGS in whom exome sequencing led to the identification of five novel de novo pathogenic variants in AHDC1. All variants were extremely rare and predicted to cause a loss of protein function. The phenotype of the reported patients included developmental delay, hypotonia, and distinctive facial dysmorphisms. Additionally, uncommon clinical features were observed, including congenital hypothyroidism and peculiar skeletal abnormalities.

Conclusions: In this study, we report uncommon XGS features associated with five novel truncating variants in AHDC, thus expanding the genotype and phenotypic spectrum of this complex condition. We also compared our cases to previously reported cases, discussing the current status of genotype-phenotype correlations in XGS.

Cinelli G, Della Vecchia S, Bergonzini P, Caramaschi E, Spezia E, Parenti C, Madeo SF, Lucaccioni L, Francesca C, Pugliese M, Raviglione F, Colonna C, Calabrese O, Stanghellini I, Marongiu MC, Biagioni E, Ferrari AR, Battini R, Iughetti L. Clinical, Behavioral and Neuroradiological Phenotype in an Italian Cohort of Patients With Xia Gibbs Syndrome: A Multicenter Cross-Sectional Study and Systematic Literature Review. Am J Med Genet A. 2026 Sep;200(9):2067-2079. doi: 10.1002/ajmg.a.70163. Epub 2026 Apr 30. PMID: 42059486.

Abstract

Heterozygous variants in the AHDC1 gene are associated with Xia Gibbs Syndrome (XGS), a genetic disorder with a highly variable phenotype. Cognitive impairment, motor delay, language delay, neonatal hypotonia, and sleep apnea are considered "cardinal" signs of the disease. In a multicenter cross-sectional study, we analyzed the genetic, epileptological, behavioral, and neuroradiological features of 15 patients with XGS harboring heterozygous variants in AHDC1. The phenotype of our patient cohort is almost overlapping with that already reported in the literature. Seizures begin between 2 and 9 years, while EEG is generally characterized by normal background activity with paroxysmal abnormalities in the posterior areas increased by sleep. We systematically analyzed brain imaging findings as the most frequent brain alteration: the thinning of the corpus callosum, followed by posterior fossa malformation and lateral ventricle morphology abnormalities. Regarding psychiatric disorders, we observed neurodevelopmental disorders such as ID, language disorders, Autism spectrum disorders (ASD), and ADHD in preschoolers, followed by a prevalence of externalizing problems during childhood and adolescence. Our study showed that epilepsy and brain anomalies are very common among XGS individuals. MRI changes are nonspecific, but their association with other clinical features of the syndrome can guide early diagnosis. EEG abnormalities are present in all epileptic patients in the temporal-occipital regions with the same characteristics, so we could hypothesize that these abnormalities could represent a recognizable EEG pattern of XGS. Behavioral disorders represent an important problem, and longitudinal evaluations are needed to improve the classification of the psychopathological spectrum in XGS.