A community in Guatemala was shocked when a teenage girl they reportedly thought was dead woke up inside her own coffin.
Fifteen-year-old Yuleidy Ixcotoyac passed out while she was in the car with her father who was driving her to a hospital, news.com.au reported Tuesday.
The teen had reportedly been having chest pains when the incident happened Saturday, and her father, Pastor Abraham Ixcotoyac, checked her pulse and breathing after he stopped their vehicle.
He claimed he could not detect any signs of life, so he believed she was dead and decided not continue the journey to the hospital. Reports said the family never received a confirmed diagnosis or death certificate for the girl and decided to proceed with her funeral which took place eight hours later, according to WION.
Burying someone soon after they die is customary in Guatemala, therefore, her family bought a coffin and placed her inside of it.
However, everyone was shocked when something incredible happened at the family’s home in El Jocote. While looking at her daughter in the casket, the girl’s mother said she saw her move and insisted that she was not dead as everyone believed.
“When I was crying on top of her casket, we opened the window, and she was moving, she was waking up, and suddenly she sat up,” the woman recalled.
Video footage showed the moment the girl was seen sitting up with friends and family around her. One person held a cup to her mouth while others clapped and shouted, “Hallelujah!”
Following the harrowing ordeal and nearly being buried alive, Yuleidy is now recovering at home.
“My heart started hurting really badly, it felt heavy and then I blacked out, like I fainted,” she told reporters.
Social media users shared their thoughts on the reports, one person writing, “And that is why it is called a ‘Wake,'” while someone else said, “There are a few steps missing here before the wake? lol.”
According to the Britannica website, the term “wake” refers to an ancient religious practice:
A wake is a religious rite that traditionally involves mourners staying awake to watch over the body of a deceased person the night before the person’s burial. The term wake has its roots in ancient customs, particularly in the British Isles. The original purpose of a wake was rooted in the belief that evil spirits might harm or even steal the body of the deceased. By staying awake and keeping watch, family and friends could protect the body from such malevolent forces. The Anglo-Saxons referred to this custom as lich-wake, with lich meaning corpse.
The teenager reportedly said she “thanks God” she is alive after the incident.
Amy Furr
https://www.breitbart.com/latin-america/2026/10/13/watch-teenager-wakes-up-inside-her-own-casket-at-funeral-in-guatemala/
Tuesday, October 13, 2026
ZNF292 mutations 2
Inspired by a patient
Shen Y, Pan R, Liu C, Zheng J, Yang X. De Novo ZNF292 Variants Cause Neurodevelopmental Disorder with Short Stature: A Clinical Case Series of Eight Individuals. Genes (Basel). 2026 Aug 13;17(8):950. doi: 10.3390/genes17080950. PMID: 42650143; PMCID: PMC13512819.
Abstract
Background: Pathogenic variants in ZNF292 cause intellectual disability type 64 (MIM#619188), characterized by intellectual impairment ranging from mild to severe, speech delay, and autism spectrum disorder. However, reports of ZNF292-related neurodevelopmental disorders remain scarce, and most published studies are based on multi-center cohorts. Methods: We performed whole-exome sequencing in eight unrelated individuals presenting with unexplained neurodevelopmental disorders, including global developmental delay and/or intellectual disability. Detailed clinical characterization, neuroimaging, and developmental assessments were conducted. Results: Seven de novo variants in ZNF292 were identified, including two nonsense and five frameshift variants, namely, c.4189C>T (p.Arg1397Ter), c.6343C>T (p.Arg2115Ter), c.1533del (p.Ile511Metfs*11), c.3094dup (p.Ser1032Phefs*18), c.3997_3998del (p.Thr1333Glnfs*8), c.6028_6031del (p.Ala2010Ter) and c.6160_6161del (p.Glu2054Lysfs*14). Among these, c.1533del (p.Ile511Metfs11), c.3094dup (p.Ser1032Phefs18) and c.3997_3998del (p.Thr1333Glnfs*8) are reported here for the first time. All variants were classified as pathogenic. All individuals exhibited global developmental delay, intellectual disability, and short stature. The majority presented with language impairment, motor delays, autism spectrum features, and dysmorphic facial features, while brain magnetic resonance imaging revealed nonspecific abnormalities such as ventriculomegaly. Conclusions: This study contributes additional cases to the expanding phenotypic and mutational spectrum of ZNF292-related neurodevelopmental disorder. Growth retardation was observed in all eight individuals, but given the limitations of a single-center referral cohort, this observation should be interpreted with caution and requires validation in larger studies.
Shen Y, Pan R, Liu C, Zheng J, Yang X. De Novo ZNF292 Variants Cause Neurodevelopmental Disorder with Short Stature: A Clinical Case Series of Eight Individuals. Genes (Basel). 2026 Aug 13;17(8):950. doi: 10.3390/genes17080950. PMID: 42650143; PMCID: PMC13512819.
Abstract
Background: Pathogenic variants in ZNF292 cause intellectual disability type 64 (MIM#619188), characterized by intellectual impairment ranging from mild to severe, speech delay, and autism spectrum disorder. However, reports of ZNF292-related neurodevelopmental disorders remain scarce, and most published studies are based on multi-center cohorts. Methods: We performed whole-exome sequencing in eight unrelated individuals presenting with unexplained neurodevelopmental disorders, including global developmental delay and/or intellectual disability. Detailed clinical characterization, neuroimaging, and developmental assessments were conducted. Results: Seven de novo variants in ZNF292 were identified, including two nonsense and five frameshift variants, namely, c.4189C>T (p.Arg1397Ter), c.6343C>T (p.Arg2115Ter), c.1533del (p.Ile511Metfs*11), c.3094dup (p.Ser1032Phefs*18), c.3997_3998del (p.Thr1333Glnfs*8), c.6028_6031del (p.Ala2010Ter) and c.6160_6161del (p.Glu2054Lysfs*14). Among these, c.1533del (p.Ile511Metfs11), c.3094dup (p.Ser1032Phefs18) and c.3997_3998del (p.Thr1333Glnfs*8) are reported here for the first time. All variants were classified as pathogenic. All individuals exhibited global developmental delay, intellectual disability, and short stature. The majority presented with language impairment, motor delays, autism spectrum features, and dysmorphic facial features, while brain magnetic resonance imaging revealed nonspecific abnormalities such as ventriculomegaly. Conclusions: This study contributes additional cases to the expanding phenotypic and mutational spectrum of ZNF292-related neurodevelopmental disorder. Growth retardation was observed in all eight individuals, but given the limitations of a single-center referral cohort, this observation should be interpreted with caution and requires validation in larger studies.
Thursday, October 8, 2026
Hao-Fountain Syndrome
Schaaf C, Sailer S. USP7-Related Hao-Fountain Syndrome. 2025 Dec 4. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2026. PMID: 41343689.cxcx/
Excerpt
Clinical characteristics: USP7-related Hao-Fountain syndrome is characterized by developmental delay in 100% of individuals, although intellectual disability is variable, with up to 50% of affected individuals having intellect in the normal range. Muscular hypotonia is also common; this tends to improve over time, but some affected individuals develop hypertonia. About two thirds of affected individuals have an abnormal/unsteady gait and about one quarter have contractures, most commonly involving large joints and joints of the lower extremities. Neuropsychiatric features can include autism, attention-deficit/hyperactivity disorder (ADHD), and behavioral issues such as stubbornness and compulsivity. Feeding difficulties are common and can require special feeding techniques, including use of a feeding tube. Gastroesophageal reflux disease, dysphagia, and hyperphagia have also been reported. Eye and vision issues (hyperopia, strabismus, nystagmus) are seen in more than 50% of affected individuals. About half of affected individuals have impaired bone mineralization, which can lead to fractures. Findings in fewer than 50% of individuals include epilepsy, sleep disturbance, hypogonadism, scoliosis, and hearing loss.
Diagnosis/testing: The diagnosis of USP7-related Hao-Fountain syndrome is established in a proband with suggestive findings and a heterozygous pathogenic variant in USP7 identified by molecular genetic testing.
Management: Treatment of manifestations: Feeding therapy for poor weight gain / dysphagia; gastrostomy tube placement may be required for persistent feeding issues; consultation with a dietician when hyperphagia and/or obesity is present; adequate intake of Ca2+ and vitamin D for reduced bone mineral density. Standard treatment for developmental delay / intellectual disability, epilepsy, gastroesophageal reflux disease, diarrhea, constipation, eye issues, sleep disturbance, cryptorchidism, micropenis, hypothyroidism, growth hormone deficiency, adrenal insufficiency, and hearing loss.
Surveillance: At each visit, measure growth parameters; evaluate nutritional status and safety of oral intake; monitor for signs/symptoms of constipation and gastroesophageal reflux disease; monitor those with seizures; assess for new manifestations such as seizures, changes in tone, and gait abnormalities; monitor developmental progress and educational needs; monitor for scoliosis, contractures, mobility, and self-help skills; monitor for evidence of aspiration, respiratory insufficiency, and sleep disturbance (including for signs/symptoms of sleep apnea); monitor for signs and symptoms of puberty starting at about age seven years to the late teenage years. Annually, behavioral assessment for anxiety, ADHD, autism spectrum disorder, aggression, and self-injury; evaluate for hypothyroidism; audiology evaluation (in childhood). Assess bone mineral density every two years starting at age five years and then every three to five years in adulthood. Ophthalmology evaluation and endocrinologic tests for adrenal insufficiency as clinically indicated.
Genetic counseling: USP7-related Hao-Fountain syndrome is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Rarely, individuals diagnosed with USP7-related Hao-Fountain syndrome inherited a pathogenic variant from a parent. Each child of an individual with USP7-related Hao-Fountain syndrome has a 50% chance of inheriting the pathogenic variant. Once the USP7 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
Korchak EJ, Sharafi M, Jaen Maisonet I, Salazar-Chaparro A, Semenova IV, Khan H, O'Neil AL, Caro P, Schaaf CP, Buhrlage SJ, Bezsonova I. Functional spectrum of USP7 pathogenic variants in Hao-Fountain syndrome: Insights into the enzyme's activity, stability, and allosteric modulation. Proc Natl Acad Sci U S A. 2025 Sep 30;122(39):e2510252122. doi: 10.1073/pnas.2510252122. Epub 2025 Sep 22. PMID: 40982686; PMCID: PMC12501124.
Abstract
Hao-Fountain syndrome is a rare neurodevelopmental disorder caused by mutations in the deubiquitinating enzyme Ubiquitin-Specific Protease 7 (USP7). Due to the novelty of the disease and its poorly understood molecular mechanisms, treatments for the syndrome are currently lacking. This study examines the effects of 11 patient-derived variants located within the catalytic domain of USP7, focusing on their impact on the enzyme's activity, thermodynamic stability, and substrate recognition. Our findings reveal a spectrum of functional consequences, ranging from complete inactivation to hyperactivation of USP7. Notably, we identify a specific subset of pathogenic variants whose catalytic activity can be significantly boosted using an allosteric activator, MS-8. These results provide insight into USP7 malfunction in Hao-Fountain syndrome-linked variants and pave the way for improved prognostic approaches and targeted treatments in the future.
Wimmer MC, Brennenstuhl H, Hirsch S, Dötsch L, Unser S, Caro P, Schaaf CP. Hao-Fountain syndrome: 32 novel patients reveal new insights into the clinical spectrum. Clin Genet. 2024 May;105(5):499-509. doi: 10.1111/cge.14480. Epub 2024 Jan 14. PMID: 38221796.
Abstract
Hao-Fountain syndrome (HAFOUS, OMIM: #616863) is a neurodevelopmental disorder caused by pathogenic variants in the gene USP7 coding for USP7, a protein involved in several crucial cellular homeostatic mechanisms and the recently described MUST complex. The phenotype of HAFOUS is insufficiently understood, yet there is a great need to better understand the spectrum of disease, genotype-phenotype correlations, and disease trajectories. We now present a larger cohort of 32 additional individuals and provide further clinical information about six previously reported individuals. A questionnaire-based study was performed to characterize the phenotype of Hao-Fountain syndrome more clearly, to highlight new traits, and to better distinguish the disease from related neurodevelopmental disorders. In addition to confirming previously described features, we report hyperphagia and increased body weight in a subset of individuals. HAFOUS patients present an increased rate of birth complications, congenital anomalies, and abnormal pain thresholds. Speech impairment emerges as a potential hallmark of Hao-Fountain syndrome. Cognitive testing reports reveal borderline intellectual functioning on average, although some individuals score in the range of intellectual disability. Finally, we created a syndrome-specific severity score. This score neither indicates a sex- nor age-specific difference of clinical severity, yet highlights a more severe outcome when amino acid changes colocalize to the catalytic domain of the USP7 protein.
Rafeienejad F, Keyhani E, Akbarfahimi N, Nouri N. Neurodevelopmental disorder: Hao-Fountain syndrome with USP7 mutation-a case report. J Med Case Rep. 2025 Jul 24;19(1):363. doi: 10.1186/s13256-025-05403-y. PMID: 40707997; PMCID: PMC12291276.
Abstract
Background: Hao-Fountain syndrome (HAFOUS) is a rare neurodevelopmental disorder manifesting as several known symptoms, including speech and language delay, behavioral abnormalities, and intellectual disability. This rare condition is usually diagnosed by heterozygous deletion or mutation in the ubiquitin-specific protease 7 gene in conjunction with phenotype features.
Case presentation: We report the case of a 5-year-old Persian girl with this rare syndrome. The process of diagnosis, from perinatal examinations to the latest laboratory and clinical tests, is described for the first time in Iran.
Conclusion: Reporting all the symptoms of such a rare genetic case in detail emphasizes the importance of interdisciplinary teamwork and the necessity of raising awareness among therapists about probable upcoming problems; sharing such evident information with parents would help them manage the complexity of raising children with rare syndromes.
Excerpt
Clinical characteristics: USP7-related Hao-Fountain syndrome is characterized by developmental delay in 100% of individuals, although intellectual disability is variable, with up to 50% of affected individuals having intellect in the normal range. Muscular hypotonia is also common; this tends to improve over time, but some affected individuals develop hypertonia. About two thirds of affected individuals have an abnormal/unsteady gait and about one quarter have contractures, most commonly involving large joints and joints of the lower extremities. Neuropsychiatric features can include autism, attention-deficit/hyperactivity disorder (ADHD), and behavioral issues such as stubbornness and compulsivity. Feeding difficulties are common and can require special feeding techniques, including use of a feeding tube. Gastroesophageal reflux disease, dysphagia, and hyperphagia have also been reported. Eye and vision issues (hyperopia, strabismus, nystagmus) are seen in more than 50% of affected individuals. About half of affected individuals have impaired bone mineralization, which can lead to fractures. Findings in fewer than 50% of individuals include epilepsy, sleep disturbance, hypogonadism, scoliosis, and hearing loss.
Diagnosis/testing: The diagnosis of USP7-related Hao-Fountain syndrome is established in a proband with suggestive findings and a heterozygous pathogenic variant in USP7 identified by molecular genetic testing.
Management: Treatment of manifestations: Feeding therapy for poor weight gain / dysphagia; gastrostomy tube placement may be required for persistent feeding issues; consultation with a dietician when hyperphagia and/or obesity is present; adequate intake of Ca2+ and vitamin D for reduced bone mineral density. Standard treatment for developmental delay / intellectual disability, epilepsy, gastroesophageal reflux disease, diarrhea, constipation, eye issues, sleep disturbance, cryptorchidism, micropenis, hypothyroidism, growth hormone deficiency, adrenal insufficiency, and hearing loss.
Surveillance: At each visit, measure growth parameters; evaluate nutritional status and safety of oral intake; monitor for signs/symptoms of constipation and gastroesophageal reflux disease; monitor those with seizures; assess for new manifestations such as seizures, changes in tone, and gait abnormalities; monitor developmental progress and educational needs; monitor for scoliosis, contractures, mobility, and self-help skills; monitor for evidence of aspiration, respiratory insufficiency, and sleep disturbance (including for signs/symptoms of sleep apnea); monitor for signs and symptoms of puberty starting at about age seven years to the late teenage years. Annually, behavioral assessment for anxiety, ADHD, autism spectrum disorder, aggression, and self-injury; evaluate for hypothyroidism; audiology evaluation (in childhood). Assess bone mineral density every two years starting at age five years and then every three to five years in adulthood. Ophthalmology evaluation and endocrinologic tests for adrenal insufficiency as clinically indicated.
Genetic counseling: USP7-related Hao-Fountain syndrome is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Rarely, individuals diagnosed with USP7-related Hao-Fountain syndrome inherited a pathogenic variant from a parent. Each child of an individual with USP7-related Hao-Fountain syndrome has a 50% chance of inheriting the pathogenic variant. Once the USP7 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
Korchak EJ, Sharafi M, Jaen Maisonet I, Salazar-Chaparro A, Semenova IV, Khan H, O'Neil AL, Caro P, Schaaf CP, Buhrlage SJ, Bezsonova I. Functional spectrum of USP7 pathogenic variants in Hao-Fountain syndrome: Insights into the enzyme's activity, stability, and allosteric modulation. Proc Natl Acad Sci U S A. 2025 Sep 30;122(39):e2510252122. doi: 10.1073/pnas.2510252122. Epub 2025 Sep 22. PMID: 40982686; PMCID: PMC12501124.
Abstract
Hao-Fountain syndrome is a rare neurodevelopmental disorder caused by mutations in the deubiquitinating enzyme Ubiquitin-Specific Protease 7 (USP7). Due to the novelty of the disease and its poorly understood molecular mechanisms, treatments for the syndrome are currently lacking. This study examines the effects of 11 patient-derived variants located within the catalytic domain of USP7, focusing on their impact on the enzyme's activity, thermodynamic stability, and substrate recognition. Our findings reveal a spectrum of functional consequences, ranging from complete inactivation to hyperactivation of USP7. Notably, we identify a specific subset of pathogenic variants whose catalytic activity can be significantly boosted using an allosteric activator, MS-8. These results provide insight into USP7 malfunction in Hao-Fountain syndrome-linked variants and pave the way for improved prognostic approaches and targeted treatments in the future.
Wimmer MC, Brennenstuhl H, Hirsch S, Dötsch L, Unser S, Caro P, Schaaf CP. Hao-Fountain syndrome: 32 novel patients reveal new insights into the clinical spectrum. Clin Genet. 2024 May;105(5):499-509. doi: 10.1111/cge.14480. Epub 2024 Jan 14. PMID: 38221796.
Abstract
Hao-Fountain syndrome (HAFOUS, OMIM: #616863) is a neurodevelopmental disorder caused by pathogenic variants in the gene USP7 coding for USP7, a protein involved in several crucial cellular homeostatic mechanisms and the recently described MUST complex. The phenotype of HAFOUS is insufficiently understood, yet there is a great need to better understand the spectrum of disease, genotype-phenotype correlations, and disease trajectories. We now present a larger cohort of 32 additional individuals and provide further clinical information about six previously reported individuals. A questionnaire-based study was performed to characterize the phenotype of Hao-Fountain syndrome more clearly, to highlight new traits, and to better distinguish the disease from related neurodevelopmental disorders. In addition to confirming previously described features, we report hyperphagia and increased body weight in a subset of individuals. HAFOUS patients present an increased rate of birth complications, congenital anomalies, and abnormal pain thresholds. Speech impairment emerges as a potential hallmark of Hao-Fountain syndrome. Cognitive testing reports reveal borderline intellectual functioning on average, although some individuals score in the range of intellectual disability. Finally, we created a syndrome-specific severity score. This score neither indicates a sex- nor age-specific difference of clinical severity, yet highlights a more severe outcome when amino acid changes colocalize to the catalytic domain of the USP7 protein.
Rafeienejad F, Keyhani E, Akbarfahimi N, Nouri N. Neurodevelopmental disorder: Hao-Fountain syndrome with USP7 mutation-a case report. J Med Case Rep. 2025 Jul 24;19(1):363. doi: 10.1186/s13256-025-05403-y. PMID: 40707997; PMCID: PMC12291276.
Abstract
Background: Hao-Fountain syndrome (HAFOUS) is a rare neurodevelopmental disorder manifesting as several known symptoms, including speech and language delay, behavioral abnormalities, and intellectual disability. This rare condition is usually diagnosed by heterozygous deletion or mutation in the ubiquitin-specific protease 7 gene in conjunction with phenotype features.
Case presentation: We report the case of a 5-year-old Persian girl with this rare syndrome. The process of diagnosis, from perinatal examinations to the latest laboratory and clinical tests, is described for the first time in Iran.
Conclusion: Reporting all the symptoms of such a rare genetic case in detail emphasizes the importance of interdisciplinary teamwork and the necessity of raising awareness among therapists about probable upcoming problems; sharing such evident information with parents would help them manage the complexity of raising children with rare syndromes.
Thursday, October 1, 2026
TUBGCP6 mutations
Inspired by a patient
Abstract
Purpose: To describe a case of microcephaly, unilateral retinal fold, and familial exudative vitreoretinopathy (FEVR)-like phenotype in the context of 2 TUBGCP6 variants. Methods: A case and its findings were analyzed. Results: A 4-month-old boy with no family history of eye disease presented by referral for management of presumed persistent fetal vasculature in the left eye. An external examination showed microcephaly. The patient grimaced to light in both eyes, and the anterior segments were unremarkable. On dilated fundus examination, diffuse chorioretinal atrophy was present bilaterally. In the left eye, a retinal fold emanated from the optic nerve head. There was early termination of retinal vasculature, especially in zone 3 in the left eye, resembling a FEVR-like phenotype. Panel-based genetic testing was performed and found 2 mutations in TUBGCP6. Conclusions: Microcephaly, chorioretinopathy, and retinal folds may be associated with TUBGCP6 mutations and masquerade as PFV.
Shurygina MF, Simonett JM, Parker MA, Mitchell A, Grigorian F, Lifton J, Nagiel A, Shpak AA, Dadali EL, Mishina IA, Weleber RG, Yang P, Pennesi ME. Genotype Phenotype Correlation and Variability in Microcephaly Associated With Chorioretinopathy or Familial Exudative Vitreoretinopathy. Invest Ophthalmol Vis Sci. 2020 Nov 2;61(13):2. doi: 10.1167/iovs.61.13.2. PMID: 33137195; PMCID: PMC7645200.
Abstract
Purpose: The purpose of this study was to analyze the natural history and phenotypic overlap of patients with microcephaly and a chorioretinopathy or familial exudative vitreoretinopathy (FEVR) ocular phenotype caused by mutations in KIF11, TUBGCP4, or TUBGCP6.
Methods: Patients diagnosed with congenital microcephaly and chorioretinopathy or FEVR were included. Molecular investigations consisted of targeted genetic sequencing. Data from medical records, ophthalmologic examination and imaging, electroretinography, and visual fields were analyzed for systemic and ophthalmic features and evidence of posterior segment disease progression.
Results: Twelve patients from 9 families were included and had a median of 8 years of follow-up. Nine patients had KIF11 variants, two had heterozygous TUBGCP6 variants, and one had heterozygous variants in TUBGCP4. All patients had reduced visual function and multiple individuals and families showed features of both chorioretinopathy and FEVR. Progression of posterior segment disease was highly variable, with some degree of increased atrophy of the macula or peripheral retina or increased vitreoretinal traction observed in 9 of 12 patients.
Conclusions: Microcephaly due to mutations in KIF11, TUBGCP4, or TUBGCP6 can be associated with retinal disease on a spectrum from chorioretinal atrophy to FEVR-like posterior segment changes. Visually significant disease progression can occur and patients should be monitored closely by a team experienced in ophthalmic genetics.
Hull S, Arno G, Ostergaard P, Pontikos N, Robson AG, Webster AR, Hogg CR, Wright GA, Henderson RHH, Martin CA, Jackson AP, Mansour S, Moore AT, Michaelides M. Clinical and Molecular Characterization of Familial Exudative Vitreoretinopathy Associated With Microcephaly. Am J Ophthalmol. 2019 Nov;207:87-98. doi: 10.1016/j.ajo.2019.05.001. Epub 2019 May 8. PMID: 31077665.
Abstract
Purpose: Familial exudative vitreoretinopathy (FEVR) is a rare finding in patients with genetic forms of microcephaly. This study documents the detailed phenotype and expands the range of genetic heterogeneity.
Design: Retrospective case series.
Methods: Twelve patients (10 families) with a diagnosis of FEVR and microcephaly were ascertained from pediatric genetic eye clinics and underwent full clinical assessment including retinal imaging. Molecular investigations included candidate gene Sanger sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS).
Results: All patients had reduced vision and nystagmus. Six were legally blind. Two probands carried bi-allelic LRP5 variants, both presenting with bilateral retinal folds. A novel homozygous splice variant, and 2 missense variants were identified. Subsequent bone density measurement identified osteoporosis in one proband. Four families had heterozygous KIF11 variants. Two probands had a retinal fold in one eye and chorioretinal atrophy in the other; the other 2 had bilateral retinal folds. Four heterozygous variants were found, including 2 large deletions not identified on Sanger sequencing or WES. Finally, a family of 2 children with learning difficulties, abnormal peripheral retinal vasculogenesis, and rod-cone dystrophy were investigated. They were found to have bi-allelic splicing variants in TUBGCP6. Three families remain unsolved following WES and WGS.
Conclusions: Molecular diagnosis has been achieved in 7 of 10 families investigated, including a previously unrecognized association with LRP5. WGS enabled molecular diagnosis in 3 families after prior negative Sanger sequencing of the causative gene. This has enabled patient-specific care with targeted investigations and accurate family counseling.
Wednesday, September 30, 2026
Epilepsy surgery
By the time Charlotte “Charli” Hilz’s family drove from Dallas to Austin, they had tried nearly everything they had been offered to control her seizures: Seven medications, dietary changes and steroids had failed. Some treatments helped briefly, while others brought difficult side effects. All the while, two-year-old Charli was losing abilities she had already developed.
Her parents knew the situation was worsening. What they did not have was a clear path forward.
“My trust began to waver,” says Charli’s father, Trevor Hilz. “But I also didn’t know where to go.”
A family connection led them to Dave Clarke, M.D., chief of the Comprehensive Pediatric Epilepsy Program within the neurology clinic at Dell Children’s, a clinical partnership with Dell Medical School that is now ranked No. 21 in the country. Within a week, they had made the trip to Austin and begun a new evaluation — one designed not simply to try another medication, but to understand why the treatments had failed and whether a more definitive option was possible.
“Our program is designed to engage closely with families and across our disciplines to get to the root of the problem,” says Clarke, professor of pediatrics and neurology at Dell Medical School at The University of Texas at Austin. “Highly trained epileptologists, neurosurgeons who are able to take on high-risk procedures if needed, neuropsychologists, social workers, advanced practice providers and nurses — we all collaborate with the child and family at the center. That’s what makes the difference here: We are both capable and willing to go the extra mile for each child.”
National recognition for Austin pediatric programs
Charli’s journey points to a larger shift in the Central Texas medical landscape. For years, families in Austin routinely traveled to Dallas, Houston and elsewhere for highly specialized pediatric care. Charli’s family came in the opposite direction, seeking capabilities that an emerging academic pediatric neuroscience program had assembled here.
Created in 2019, the program brought pediatric neurology, neurosurgery, neuropsychology, neuro-ophthalmology, rehabilitation and related specialties into a more integrated model. It earned its first national recognition from U.S. News & World Report three years later. By 2025, the program had reached No. 25 in the country for pediatric neurology and neurosurgery. Today, it is tied for No. 21, one of a handful of programs led by Dell Med faculty now climbing in national recognition.
“The power of academic medicine is that patient care, research and education continually strengthen one another,” says Claudia Lucchinetti, M.D., senior vice president for medical affairs and dean of Dell Medical School at The University of Texas at Austin. “The needs of patients shape research, new discoveries create better outcomes, and education prepares more physicians to deliver the most advanced care. At Dell Children’s, Dell Med faculty bring that model together with outstanding clinical teams and the broader capabilities of UT to take on complex cases and find a path forward when standard answers fall short.
“These rankings reflect what matters for children and families: deeper expertise, more options, and access to nationally recognized care here in Central Texas.”
Charli’s journey from uncertainty to recovery
Other leading pediatric epilepsy centers around the country have access to many of the same advanced tools. But what Charli and her family needed — and had not yet found — was a team of advanced specialists prepared to put them together around her particular case.
“When advanced specialists come together, we can look at complex cases from every angle,” says Adam Messer, president of Dell Children’s Medical Center. “This collaboration helps us understand each child’s unique needs so we can provide comprehensive care that supports the entire family.”
Charli’s epilepsy began in one area of the brain but spread so rapidly that it could resemble a different type of seizure disorder. At the same time, abnormal electrical activity was disrupting more than half of her sleep, interfering with her brain’s ability to rest, learn and develop. She was having as many as 20 seizures a day, struggling to walk and speak clearly, and losing the use of her left hand.
At Dell Children’s, the team began again with inpatient monitoring, capturing Charli’s seizures and studying the electrical activity in her brain. Advanced imaging helped narrow the suspected source. Epileptologists, neurosurgeons and neuropsychologists then used stereo-EEG, placing small electrodes in and around the target area to determine precisely where her seizures began and how closely that area bordered functions that needed to be preserved.
The evaluation located a small area of atypical cells near Charli’s sensory cortex. The target was so tightly surrounded by functional tissue that conventional surgical removal could have caused harm.
Instead, the team guided a needle-sized probe between two folds of her brain and used laser energy to deactivate the cells driving the seizures while protecting the surrounding tissue.
Today, Charli is six years old and remains seizure-free. Her overnight epileptic episodes have largely disappeared. She is using both sides of her body more fully, taking fewer medications and rapidly regaining function her family once feared had been permanently lost.
“For the first time, we felt heard,” says Charli’s mother, Mackenzie Hilz. “Dr. Clarke believed us. He looked at her and us and said, ‘I have a plan.’ We hadn’t heard that from anyone before. We took the leap, and it saved her life.”
https://news.utexas.edu/2026/09/17/academic-medicine-raises-the-bar-for-pediatric-neuroscience-care-in-austin/
Her parents knew the situation was worsening. What they did not have was a clear path forward.
“My trust began to waver,” says Charli’s father, Trevor Hilz. “But I also didn’t know where to go.”
A family connection led them to Dave Clarke, M.D., chief of the Comprehensive Pediatric Epilepsy Program within the neurology clinic at Dell Children’s, a clinical partnership with Dell Medical School that is now ranked No. 21 in the country. Within a week, they had made the trip to Austin and begun a new evaluation — one designed not simply to try another medication, but to understand why the treatments had failed and whether a more definitive option was possible.
“Our program is designed to engage closely with families and across our disciplines to get to the root of the problem,” says Clarke, professor of pediatrics and neurology at Dell Medical School at The University of Texas at Austin. “Highly trained epileptologists, neurosurgeons who are able to take on high-risk procedures if needed, neuropsychologists, social workers, advanced practice providers and nurses — we all collaborate with the child and family at the center. That’s what makes the difference here: We are both capable and willing to go the extra mile for each child.”
National recognition for Austin pediatric programs
Charli’s journey points to a larger shift in the Central Texas medical landscape. For years, families in Austin routinely traveled to Dallas, Houston and elsewhere for highly specialized pediatric care. Charli’s family came in the opposite direction, seeking capabilities that an emerging academic pediatric neuroscience program had assembled here.
Created in 2019, the program brought pediatric neurology, neurosurgery, neuropsychology, neuro-ophthalmology, rehabilitation and related specialties into a more integrated model. It earned its first national recognition from U.S. News & World Report three years later. By 2025, the program had reached No. 25 in the country for pediatric neurology and neurosurgery. Today, it is tied for No. 21, one of a handful of programs led by Dell Med faculty now climbing in national recognition.
“The power of academic medicine is that patient care, research and education continually strengthen one another,” says Claudia Lucchinetti, M.D., senior vice president for medical affairs and dean of Dell Medical School at The University of Texas at Austin. “The needs of patients shape research, new discoveries create better outcomes, and education prepares more physicians to deliver the most advanced care. At Dell Children’s, Dell Med faculty bring that model together with outstanding clinical teams and the broader capabilities of UT to take on complex cases and find a path forward when standard answers fall short.
“These rankings reflect what matters for children and families: deeper expertise, more options, and access to nationally recognized care here in Central Texas.”
Charli’s journey from uncertainty to recovery
Other leading pediatric epilepsy centers around the country have access to many of the same advanced tools. But what Charli and her family needed — and had not yet found — was a team of advanced specialists prepared to put them together around her particular case.
“When advanced specialists come together, we can look at complex cases from every angle,” says Adam Messer, president of Dell Children’s Medical Center. “This collaboration helps us understand each child’s unique needs so we can provide comprehensive care that supports the entire family.”
Charli’s epilepsy began in one area of the brain but spread so rapidly that it could resemble a different type of seizure disorder. At the same time, abnormal electrical activity was disrupting more than half of her sleep, interfering with her brain’s ability to rest, learn and develop. She was having as many as 20 seizures a day, struggling to walk and speak clearly, and losing the use of her left hand.
At Dell Children’s, the team began again with inpatient monitoring, capturing Charli’s seizures and studying the electrical activity in her brain. Advanced imaging helped narrow the suspected source. Epileptologists, neurosurgeons and neuropsychologists then used stereo-EEG, placing small electrodes in and around the target area to determine precisely where her seizures began and how closely that area bordered functions that needed to be preserved.
The evaluation located a small area of atypical cells near Charli’s sensory cortex. The target was so tightly surrounded by functional tissue that conventional surgical removal could have caused harm.
Instead, the team guided a needle-sized probe between two folds of her brain and used laser energy to deactivate the cells driving the seizures while protecting the surrounding tissue.
Today, Charli is six years old and remains seizure-free. Her overnight epileptic episodes have largely disappeared. She is using both sides of her body more fully, taking fewer medications and rapidly regaining function her family once feared had been permanently lost.
“For the first time, we felt heard,” says Charli’s mother, Mackenzie Hilz. “Dr. Clarke believed us. He looked at her and us and said, ‘I have a plan.’ We hadn’t heard that from anyone before. We took the leap, and it saved her life.”
https://news.utexas.edu/2026/09/17/academic-medicine-raises-the-bar-for-pediatric-neuroscience-care-in-austin/
Diazepam Intensol shortage
It seems there is a nationwide shortage of inexpensive but effective Diazepam Intensol, forcing obscenely expensive Valtoco to be prescribed in yet more obscenely expensive 5 packs.
Tuesday, September 29, 2026
Great experiments 5
Courtesy of a colleague
Hot air? BMJ. 2001 Dec 22;323(7327):1449. PMCID: PMC1121900.
“It all started with an enquiry from a nurse,” Dr Karl Kruszelnicki told listeners to his science phone-in show on the Triple J radio station in Brisbane. “She wanted to know whether she was contaminating the operating theatre she worked in by quietly farting in the sterile environment during operations, and I realised that I didn't know. But I was determined to find out.”
Dr Kruszelnicki then described the method by which he had established whether human flatus was germ-laden, or merely malodorous. “I contacted Luke Tennent, a microbiologist in Canberra, and together we devised an experiment. He asked a colleague to break wind directly onto two Petri dishes from a distance of 5 centimetres, first fully clothed, then with his trousers down. Then he observed what happened. Overnight, the second Petri dish sprouted visible lumps of two types of bacteria that are usually found only in the gut and on the skin. But the flatus which had passed through clothing caused no bacteria to sprout, which suggests that clothing acts as a filter.
“Our deduction is that the enteric zone in the second Petri dish was caused by the flatus itself, and the splatter ring around that was caused by the sheer velocity of the fart, which blew skin bacteria from the cheeks and blasted it onto the dish. It seems, therefore, that flatus can cause infection if the emitter is naked, but not if he or she is clothed. But the results of the experiment should not be considered alarming, because neither type of bacterium is harmful. In fact, they're similar to the ‘friendly’ bacteria found in yoghurt.
“Our final conclusion? Don't fart naked near food. All right, it's not rocket science. But then again, maybe it is?”
Hot air? BMJ. 2001 Dec 22;323(7327):1449. PMCID: PMC1121900.
“It all started with an enquiry from a nurse,” Dr Karl Kruszelnicki told listeners to his science phone-in show on the Triple J radio station in Brisbane. “She wanted to know whether she was contaminating the operating theatre she worked in by quietly farting in the sterile environment during operations, and I realised that I didn't know. But I was determined to find out.”
Dr Kruszelnicki then described the method by which he had established whether human flatus was germ-laden, or merely malodorous. “I contacted Luke Tennent, a microbiologist in Canberra, and together we devised an experiment. He asked a colleague to break wind directly onto two Petri dishes from a distance of 5 centimetres, first fully clothed, then with his trousers down. Then he observed what happened. Overnight, the second Petri dish sprouted visible lumps of two types of bacteria that are usually found only in the gut and on the skin. But the flatus which had passed through clothing caused no bacteria to sprout, which suggests that clothing acts as a filter.
“Our deduction is that the enteric zone in the second Petri dish was caused by the flatus itself, and the splatter ring around that was caused by the sheer velocity of the fart, which blew skin bacteria from the cheeks and blasted it onto the dish. It seems, therefore, that flatus can cause infection if the emitter is naked, but not if he or she is clothed. But the results of the experiment should not be considered alarming, because neither type of bacterium is harmful. In fact, they're similar to the ‘friendly’ bacteria found in yoghurt.
“Our final conclusion? Don't fart naked near food. All right, it's not rocket science. But then again, maybe it is?”
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