-
Cureus May 2024Cyclin-dependent kinase 13 (CDK13)-related disorder is a rare autosomal dominant disease caused by pathogenic variants in the gene. This disorder was found to be...
Cyclin-dependent kinase 13 (CDK13)-related disorder is a rare autosomal dominant disease caused by pathogenic variants in the gene. This disorder was found to be related to several clinical features, including structural cardiac anomalies, developmental delay, anomalies of the corpus callosum, and a variety of facial dysmorphisms. In addition, feeding difficulties and neonatal hypotonia might also present. The diagnosis of this disorder is based on molecular genetic testing to detect the causative pathogenic variants. Here, we report a case of a one-year-old girl from Yemen, residing in Bahrain, with a CDK13-related disorder who was found to have an unusual association of abdominal situs inversus along with multiple structural cardiac anomalies, including atrial septal defect, ventricular septal defect, patent ductus arteriosus, interrupted inferior vena cava, bilateral superior vena cava, mild coarctation of the aorta, dilated coronary sinuses, and mild regurgitation in the tricuspid valve. Moreover, facial dysmorphism including medial epicanthal folds, posteriorly rotated ears, and a depressed nasal bridge was also noted. Further assessment showed a delay in reaching developmental milestones, including speech and motor delay. The patient also presented with recurrent episodes of upper respiratory tract infections, acute bronchiolitis, and lobar pneumonia which required admission to the intensive care unit and ventilation. The last infection episode was at the age of one year. Thereafter, the patient underwent cardiac repair of the ventricular septal defect followed by no more infection episodes until the age of one year and two months. The diagnosis of CDK13 was confirmed by a whole exome sequencing test which demonstrated a novel missense variant in exon 14 of the gene as a variant of uncertain significance in a heterozygous state.
PubMed: 38910624
DOI: 10.7759/cureus.60970 -
Brain Injury Jun 2024Early Exercise Intolerance (EEI) is associated with delayed recovery and longer time to Return To Play (RTP), but this has not been established.Participants; ( = 52,...
Does early exercise intolerance effect time to return to play, symptom burden, neurocognition, Vestibular-Ocular-Motor (VOM) function and academic ability in acutely concussed student-athletes?
INTRODUCTION
Early Exercise Intolerance (EEI) is associated with delayed recovery and longer time to Return To Play (RTP), but this has not been established.Participants; ( = 52, male = 30) UK university-aged rugby-union student-athletes.
METHODS
Student-athletes completed baseline screening (July-October 2021 and 2022). The test battery was repeated within 48 h, 4, 8 and 14 days after a Sports-Related Concussion (SRC) with the Buffalo Concussion Bike or Treadmill Test to set sub-symptom heart rate threshold. Student-athletes then completed a controlled early exercise protocol in-between reassessment (days 3, 5-7 and 9-13). Those with EEI were compared to those with early-exercise tolerance.
OUTCOME MEASURES
Post-Concussion Symptom Scale, Immediate Post-Concussion and Cognitive Test, Vestibular-Ocular Motor Screening Tool and the Revised Perceived Academic Impact Tool.
RESULTS
EEI was seen throughout the initial 14-days post-SRC (23.8%, 22.4%, 25.5%. 25.0%). EEI was associated with a slower reaction time within 48 h (-0.01 (-0.030-0.043) Vs 0.06 (0.033-0.24), = 0.004) and greater VOMS scores within 48 h; (0.00 (0.00-4.00) Vs 5.50 (2.75-9.00), = 0.016) and 4 days (0.00 (0.00-2.00) Vs 5.00 (0.00-6.00), = 0.044). RTP was 12.5 days longer in those with EEI at 14-days post-SRC.
CONCLUSION
EEI is prevalent following an SRC in university-aged student-athletes and was associated with delayed recovery and RTP.
PubMed: 38910338
DOI: 10.1080/02699052.2024.2367477 -
Biological Research Jun 2024Prenatal alcohol exposure (PAE) has serious physical consequences for children such as behavioral disabilities, growth disorders, neuromuscular problems, impaired motor...
BACKGROUND
Prenatal alcohol exposure (PAE) has serious physical consequences for children such as behavioral disabilities, growth disorders, neuromuscular problems, impaired motor coordination, and decreased muscle tone. However, it is not known whether loss of muscle strength occurs, and which interventions will effectively mitigate physical PAE impairments. We aimed to investigate whether physical alteration persists during adolescence and whether exercise is an effective intervention.
RESULTS
Using paradigms to evaluate different physical qualities, we described that early adolescent PAE animals have significant alterations in agility and strength, without alterations in balance and coordination compared to CTRL animals. We evaluated the effectiveness of 3 different exercise protocols for 4 weeks: Enrichment environment (EE), Endurance exercise (EEX), and Resistance exercise (REX). The enriched environment significantly improved the strength in the PAE group but not in the CTRL group whose strength parameters were maintained even during exercise. Resistance exercise showed the greatest benefits in gaining strength, and endurance exercise did not.
CONCLUSION
PAE induced a significant decrease in strength compared to CTRL in PND21. Resistance exercise is the most effective to reverse the effects of PAE on muscular strength. Our data suggests that individualized, scheduled, and supervised training of resistance is more beneficial than endurance or enriched environment exercise for adolescents FASD.
Topics: Fetal Alcohol Spectrum Disorders; Animals; Disease Models, Animal; Physical Conditioning, Animal; Female; Muscle Strength; Pregnancy; Male; Rats; Prenatal Exposure Delayed Effects; Rats, Wistar
PubMed: 38907274
DOI: 10.1186/s40659-024-00520-2 -
European Child & Adolescent Psychiatry Jun 2024Klinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations...
BACKGROUND
Klinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations in functional brain connectivity or pubertal delays are associated with aberrant cognitive-behavioral outcomes in individuals with KS is largely unknown. In this observational study, we investigated KS-related alterations in the resting-state brain network, testosterone level, and cognitive-behavioral impairment in adolescents with Klinefelter syndrome.
METHODS
We recruited 46 boys with KS, ages 8 to 17 years, and 51 age-matched typically developing (TD) boys. All participants underwent resting-state functional magnetic resonance imaging scans, pubertal, and cognitive-behavioral assessments. Resting-state functional connectivity and regional brain activity of the participants were assessed.
RESULTS
We found widespread alterations in global functional connectivity among the inferior frontal gyrus, temporal-parietal area, and hippocampus in boys with KS. Aberrant regional activities, including enhanced fALFF in the motor area and reduced ReHo in the caudate, were also found in the KS group compared to the TD children. Further, using machine learning methods, brain network alterations in these regions accurately differentiated boys with KS from TD controls. Finally, we showed that the alterations of brain network properties not only effectively predict cognitive-behavioral impairment in boys with KS, but also appear to mediate the association between total testosterone level and language ability, a cognitive domain at particular risk for dysfunction in this condition.
CONCLUSION
Our results offer an informatic neurobiological foundation for understanding cognitive-behavioral impairments in individuals with KS and contribute to our understanding of the interplay between pubertal status, brain function, and cognitive-behavioral outcome in this population.
PubMed: 38904702
DOI: 10.1007/s00787-024-02501-y -
Frontiers in Psychology 2024Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal, and fast-progressive neurodegenerative disease characterized by the degeneration of motor neurons. ALS...
Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal, and fast-progressive neurodegenerative disease characterized by the degeneration of motor neurons. ALS patients often experience an initial misdiagnosis or a diagnostic delay due to the current unavailability of an efficient biomarker. Since impaired speech is typical in ALS, we hypothesized that functional differences between healthy and ALS participants during speech tasks can be explained by cortical pattern changes, thereby leading to the identification of a neural biomarker for ALS. In this pilot study, we collected magnetoencephalography (MEG) recordings from three early-diagnosed patients with ALS and three healthy controls during imagined (covert) and overt speech tasks. First, we computed sensor correlations, which showed greater correlations for speakers with ALS than healthy controls. Second, we compared the power of the MEG signals in canonical bands between the two groups, which showed greater dissimilarity in the beta band for ALS participants. Third, we assessed differences in functional connectivity, which showed greater beta band connectivity for ALS than healthy controls. Finally, we performed single-trial classification, which resulted in highest performance with beta band features (∼ 98%). These findings were consistent across trials, phrases, and participants for both imagined and overt speech tasks. Our preliminary results indicate that speech-evoked beta oscillations could be a potential neural biomarker for diagnosing ALS. To our knowledge, this is the first demonstration of the detection of ALS from single-trial neural signals.
PubMed: 38903475
DOI: 10.3389/fpsyg.2024.1114811 -
The American Journal of Case Reports Jun 2024BACKGROUND Fetus in fetu (FIF), or parasitic fetus, is a rare malformation that typically occurs in the retroperitoneum, but can be found in other unusual locations,...
BACKGROUND Fetus in fetu (FIF), or parasitic fetus, is a rare malformation that typically occurs in the retroperitoneum, but can be found in other unusual locations, such as the skull, sacrum, and mouth. The presence of a spine is necessary for diagnosis. CASE REPORT Intracranial FIFs were retrospectively studied. Abnormalities were detected in the fetal head during a 33-week prenatal examination; however, MRI could not provide more information, due to space occupation. A baby girl was born via cesarean delivery at 37 weeks, with a large head circumference. She had delays in motor skills and speech development, only able to say "mom". There was a large mass in the cerebral hemisphere, with a 13-cm maximum diameter, smooth boundary, and internal bone structure visible on head CT scan. Both ventricles and third ventricle had hydrops, with a fetal shape at a continuous level, along with apparent compression near the cerebral parenchyma. After performing preoperative examinations, laboratory tests, and surgical planning, craniotomy was performed on the FIF, under general anesthesia. Following complete mass resection, mouth, eye, arm, and hand shapes could be observed. The patient was unconscious after surgery and had seizures that were difficult to control. She died 12 days after surgery. Teratomas can be distinguished based on anatomy and imaging. Surgical resection is the only curative treatment and its prognosis is poor. CONCLUSIONS Intracranial FIF cases are rare and require early diagnosis and surgical treatment. Differentiating between FIF and teratoma is crucial, and monitoring alpha-fetoprotein levels after surgery can help detect recurrence.
Topics: Humans; Female; Infant, Newborn; Prognosis; Teratoma; Pregnancy; Fetus; Brain Neoplasms; Fatal Outcome; Craniotomy; Magnetic Resonance Imaging; Adult; Tomography, X-Ray Computed
PubMed: 38902917
DOI: 10.12659/AJCR.944371 -
Journal of Acquired Immune Deficiency... Jun 2024We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala,...
We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala, Uganda (32 virally suppressed [<400 copies/mL] PHIV and 57 socio-demographically matched HIV- controls) completed a tablet-based neurocognitive test battery. Control derived z-scores for 12 individual tests and a global/overall z-score were calculated. We measured plasma (soluble CD14 and CD163), monocyte (proportions of monocyte subsets), and T cell (expression of CD38 and HLA-DR on CD4+ and CD8+) activation and gut markers. Spearman's rank correlations and median regressions examined associations between test performance and immune activation. Median [IQR] age was 15[13-16] years, 40% were females. Median time on ART was 10 years [7-11] for PHIV; 87% had viral load <50 copies/mL. Compared to controls, global z-scores were lower among PHIV (p=0.05), and significantly worse on tests of executive functioning and delayed recall (p's≤0.05). Overall, monocyte activation significantly correlated with worse test performance on global z-score (r=0.21, p=0.04), attention, processing speed, and motor speed (r=0.2-0.3, p≤0.01). T cell activation was significantly correlated with worse performance on tests of learning, executive functioning, and working memory (r=0.2-0.4, p≤0.04). In PHIV, after adjusting for age, sex, and ART duration, activated CD4 T cells remained associated with worse memory (β-0.3, 95% CI, -0.55, -.07, p=0.01). PHIV with virologic suppression on ART show evidence of worse neurocognitive test performance compared to controls. Monocyte and T cell activation is correlated with worse neurocognition in Ugandan youth with and without HIV which has not been previously investigated in this setting.
PubMed: 38902861
DOI: 10.1097/QAI.0000000000003483 -
Journal of Human Genetics Jun 2024Glycosylphosphatidylinositol (GPI)-anchored proteins are located at the cell surface by a covalent attachment between protein and GPI embedded in the plasma membrane....
Glycosylphosphatidylinositol (GPI)-anchored proteins are located at the cell surface by a covalent attachment between protein and GPI embedded in the plasma membrane. This attachment is catalyzed by GPI transamidase comprising five subunits (PIGK, PIGS, PIGT, PIGU, and GPAA1) in the endoplasmic reticulum. Loss of either subunit of GPI transamidase eliminates cell surface localization of GPI-anchored proteins. In humans, pathogenic variants in either subunit of GPI transamidase cause neurodevelopmental disorders. However, how the loss of GPI-anchored proteins triggers neurodevelopmental defects remains largely unclear. Here, we identified a novel homozygous variant of PIGK, NM_005482:c.481A > G,p. (Met161Val), in a Japanese female patient with neurodevelopmental delay, hypotonia, cerebellar atrophy, febrile seizures, hearing loss, growth impairment, dysmorphic facial features, and brachydactyly. The missense variant was found heterozygous in her father, but not in her mother. Zygosity analysis revealed that the homozygous PIGK variant in the patient was caused by paternal isodisomy. Rescue experiments using PIGK-deficient CHO cells revealed that the p.Met161Val variant of PIGK reduced GPI transamidase activity. Rescue experiments using pigk mutant zebrafish confirmed that the p.Met161Val variant compromised PIGK function in tactile-evoked motor response. We also demonstrated that axonal localization of voltage-gated sodium channels and concomitant generation of action potentials were impaired in pigk-deficient neurons in zebrafish, suggesting a link between GPI-anchored proteins and neuronal defects. Taken together, the missense p.Met161Val variant of PIGK is a novel pathogenic variant that causes the neurodevelopmental disorder.
PubMed: 38902431
DOI: 10.1038/s10038-024-01264-3 -
Therapeutic Advances in Rare Disease 2024Syntaxin-binding protein 1 related disorder (STXBP1-RD) is a rare neurologic disorder associated with global neurodevelopmental delay, intellectual disability,... (Review)
Review
Syntaxin-binding protein 1 related disorder (STXBP1-RD) is a rare neurologic disorder associated with global neurodevelopmental delay, intellectual disability, early-onset epilepsy, motor abnormalities, and autism. The underlying pathophysiology stems from a mutation in the gene, which codes for the STXBP1 protein. The STXBP1 protein is involved in synaptic vesicle fusion and neurotransmitter release. Pathogenic variants in the gene generally result in haploinsufficiency, an impairment in neurotransmitter release, and subsequent dysfunction in neuronal communication. The STXBP1 Foundation was founded in 2017 to support families of children with STXBP1-RD and accelerate the development of effective therapies and, ultimately, a cure for the disorder. The Foundation initially supported research aimed at better understanding the complex phenotypic presentation of the disease as well as the development of animal and cellular models usable by the research community to more fully characterize STXBP1 function and disease pathogenicity. In 2023, the Foundation embarked on its STXBP1 Fast Forward Strategic Plan, which includes a prospective natural history study and substantive biomarker work to drive forward the development of new precision therapies for STXBP1-RD.
PubMed: 38898886
DOI: 10.1177/26330040241257221 -
Obstetrics & Gynecology Science Jun 2024To assess prenatal ultrasonographic findings and postnatal outcomes in fetuses with intracranial hemorrhage (ICH).
OBJECTIVE
To assess prenatal ultrasonographic findings and postnatal outcomes in fetuses with intracranial hemorrhage (ICH).
METHODS
This retrospective study included fetuses prenatally diagnosed with ICH between December 2012 and August 2023. Maternal characteristics, prenatal ultrasonographic findings, and postnatal outcomes were reviewed.
RESULTS
Twenty-seven fetuses with ICH were reviewed. Intracranial hemorrhage was classified as grade 3-4 in 24 fetuses. Twenty-two fetuses had ICH, four had ICH with subdural hemorrhage, and one had ICH with subarachnoid hemorrhage. Ventriculomegaly was the most common ultrasonographic finding, and was observed in 22 of the 27 (81.5%) fetuses. Seven fetuses were lost to follow-up, and four intrauterine fetal deaths occurred. The remaining 16 fetuses were delivered at a median gestational age of 35±2 weeks. The infants were followed-up for 40.1 months (range, 4-88). Nine of the 16 infants underwent ventriculoperitoneal placement. One infant underwent brain surgery for severe epilepsy. Motor impairment, including cerebral palsy, was observed in 13 (81.2%) infants. Neurologic impairment occurred in six (37.5%) infants, developmental delay in nine (56.2%), and epilepsy in 11 (68.7%).
CONCLUSION
Fetal ICH is a rare complication diagnosed during pregnancy, which results in subsequent fetal neurological sequelae or death. This study demonstrated that the common ultrasonographic findings in fetal ICH were progressive ventriculomegaly and increased periventricular echogenicity. Fetuses diagnosed with prenatal ICH, especially those affected by higher-grade ICH, may be at an increased risk of long-term neurodevelopmental problems.
PubMed: 38898776
DOI: 10.5468/ogs.24097