OBJECTIVE: To investigate the clinical manifestations and genetic etiology of a fetus with Neurodevelopmental disorders with deformed facial features and distal skeletal abnormalities (NEDDFSA). METHODS: Clinical data of a NEDDFSA fetus diagnosed at the Affiliated Women and Children's Hospital Affiliated to Ningbo University in March 2025 was selected as the study subject. Whole-exome sequencing (WES) was carried out on the amniotic fluid and parental peripheral blood samples, and candidate variants was verified by Sanger sequencing. The pathogenicity of candidate variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: At 30 weeks of gestation, the fetus was found to have microcephaly, short femur and intrauterine growth restriction. WES revealed that the fetus harbored a de novo heterozygous frameshift variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene, which was rated as pathogenic (PM2_Supporting+PS2_Supporting+PVS1). Combined with 25 cases from the literature, the main manifestations of patients have included intellectual disability, growth retardation and cranio-limb skeletal dysplasia, albeit without clear genotype-phenotype correlation. CONCLUSION The de novo variant c.2633dup (p.Gly879ArgfsTer22) of the ZMIZ1 gene probably underlay the NEDDFSA in this fetus. Genetic testing has enabled accurate prenatal diagnosis and provided evidence for genetic counseling and reproductive guidance of this family.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/genetics* ; Transcription Factors/genetics* ; Fetus/abnormalities* ; Exome Sequencing ; Prenatal Diagnosis

This study explores the impact of perceived stress on the academic performance of orthopaedic surgery residents in the Philippines. Conducted as a cross-sectional investigation, it involved 126 residents who participated in the 2024 Philippine Board of Orthopaedics In-Service Training Examination (ITE). Stress levels were assessed using the Perceived Stress Scale-10 (PSS-10), while ITE scores served as the measure of academic performance. A significant negative correlation was identified between stress and academic performance (r = -0.3138, p = 0.00010). Residents experiencing high stress achieved lower scores (55.2%) compared to those with low to moderate stress (61.8%). Other demographic variables such as sex, age, marital status and type of training institution (public and private) were not significantly associated with stress level findings. On the other hand, key factors contributing to elevated stress included insufficient sleep (0–4 hours nightly; OR = 5.83, p = 0.0289) and limited awareness of mental health issues (OR = 13.34, p = 0.0014). These results highlight the pressing need for stress reduction initiatives, improved mental health education and strategies to address challenges posed by sleep deprivation and extensive work hours. This study provides a foundation for improving both academic outcomes and overall well-being in residency programs.

Human ; Male ; Female ; Adult: 25-44 Yrs Old ; World Health Organization ; Sleep Deprivation ; Internship And Residency ; Health Education ; Cross-sectional Studies ; Marital Status

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease. METHODS: A child with neurodevelopmental disorder caused by homozygous variant of TRAPPC6B gene who was admitted to the Children's Hospital Affiliated to Zhengzhou University in March 2023 due to "inability to stand and walk independently at 1 year and 3 months old" was selected as the study object. The clinical data were collected by retrospective analysis method. Target region high-throughput sequencing was carried out on the child and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). The study has been approved by the Medical Ethics Committee of the Children's Hospital Affiliated to Zhengzhou University (Ethic No.2022-K-L025). RESULTS: The child was a 1-year-and-3-months-old boy whose parents were sib mating. The child presented with global developmental delay, microcephaly and short stature. MRI showed poor white matter myelination, abnormal signals of bilateral periventricular white matter and bilateral external sac, thin corpus callosum, and widening of the third ventricle. Genetic testing revealed that the TRAPPC6B gene of the child had a homozygous variant of c.240_241delAA (p.Q80Hfs*34), which was inherited from his parents. According to the ACMG guidelines, this variant was judged to be potentially pathogenic (PVS1_Strong+PM2_Supporting+PM3_Supporting), resulting in premature occurrence of terminator codons and a change in the three-dimensional structure of protein. The variant was located in the functional domain, which may directly affect the functional domain of the protein, resulting in functional domain defects. CONCLUSION The frameshift variation of TRAPPC6B gene c.240_241delAA (p.Q80Hfs*34) has not been reported, which may be the genetic cause of neurodevelopmental disorders in child in this study. These findings expand the variation spectrum of TRAPPC6B gene and provide basis for genetic counseling and prenatal diagnosis of this family.
Humans ; Infant ; Male ; Frameshift Mutation ; Homozygote ; Neurodevelopmental Disorders/genetics* ; Phenotype

OBJECTIVE: To investigate the clinical and genetic characteristics of a Chinese pedigree affected with Neurodevelopmental disorder with absent language and variable seizures (NEDALVS) due to variant of WASF1 gene, and to review the literature on NEDALVS associated with WASF1 gene variants. METHODS: A 4-year-and-8-month-old boy with NEDALVS diagnosed at Linyi People's Hospital in July 2024 due to "discovering language development delay for more than 2 years" and his family members were selected as the study subjects. Clinical data of the family members were collected. Peripheral venous blood samples were collected from family members. Whole-exome sequencing (WES) was performed, and candidate variants were verified, by Sanger sequencing. Pathogenicity of candidate variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG). Using the MUpro website, SWISS-MODEL, PyMOL, Clustal X, PolyPhen-2, and Mutation Taster software, bioinformatics analysis of protein three-dimensional structure modeling for gene mutations, cross-species conservation of mutant amino acids, and pathogenicity prediction of mutation sites. Relevant literature was retrieved from databases such as CNKI, Wanfang Data Knowledge Service Platform, and PubMed, and the clinical phenotypes and genotypes of patients with WASF1 gene mutations reported in the literature were summarized and analyzed. This study was approved by the Medical Ethics Committee of Linyi People's Hospital (Ethics No.: YX200303). RESULTS: The proband, a 4-year and 8-month-old male, mainly presented with delayed language and motor development, accompanied by autistic behaviors; the proband's younger brother was 2 years and 7 months old at the time of consultation, mainly presented with delayed language and motor development, accompanied by short stature; the proband's mother mainly presents with limited language expression and poor interpersonal interaction; the proband's maternal grandmother mainly presents with soliloquizing?behavior. The results of WES showed that the proband carried a heterozygous mutation c.214C>T (p.Arg72Cys) in the WASF1 gene, and this site has not been recorded in the database. Sanger sequencing confirmed that the proband's younger brother, mother, and maternal grandmother had harbored the same variant. Based on the guidelines from the ACMG, this variant was rated as likely pathogenic (PM2_Supporting+PP1+PP3+PP4). Through SWISS-MODEL homology modeling and PyMOL structure visualization analysis, it was further confirmed that this variant can lead to a decrease in protein stability. Amino acid sequence conservation analysis of the WASF1 protein using Clustal X software suggested that the c.214C>T (p.Arg72Cys) variant has caused replacement of a highly conserved amino acid. According to the results of PolyPhen-2 and Mutation Taster, the p.Arg72Cys variant was predicted to be a hazardous. By following the retrieval strategy set in this study, a total of 5 research articles regarding to patients with NEDALVS caused by WASF1 gene mutations were retrieved, which involved 15 patients. Combining the proband and their family members discovered in this study, there were a total of 19 NEDALVS patients. The main clinical features included: motor developmental delay (100%, 17/17), language/intellectual developmental delay (100%, 17/17), epilepsy (64.7%, 11/17), autistic behavior (76.5%, 13/17), hypotonia (70.6%, 12/17), abnormal electroencephalogram (64.7%, 11/17), and short stature (17.6%, 3/17). All 19 patients had heterozygous mutations, with 8 mutation sites. Missense mutations were the most common, accounting for 84.2% (16/19). CONCLUSION A pathogenic variant of the WASF1 gene was identified in a pedigree affected with NEDALVS. Discovery of the novel variant has, expanded the mutational spectrum of the WASF1 gene.
Child, Preschool ; Female ; Humans ; Infant ; Male ; China ; Exome Sequencing ; Mutation ; Neurodevelopmental Disorders/genetics* ; Pedigree ; Seizures/genetics* ; East Asian People/genetics*

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by the abnormal expansion of CAG trinucleotide repeats in the Huntingtin gene (HTT) located on chromosome 4. It is transmitted in an autosomal dominant manner and is characterized by motor dysfunction, cognitive decline, and emotional disturbances. To date, there are no curative treatments for HD have been developed; current therapeutic approaches focus on symptom relief and comprehensive care through coordinated pharmacological and nonpharmacological methods to manage the diverse phenotypes of the disease. International clinical guidelines for the treatment of HD are continually being revised in an effort to enhance care within a multidisciplinary framework. Additionally, innovative gene and cell therapy strategies are being actively researched and developed to address the complexities of the disorder and improve treatment outcomes. This review endeavours to elucidate the current and emerging gene and cell therapy strategies for HD, offering a detailed insight into the complexities of the disorder and looking forward to future treatment paradigms. Considering the complexity of the underlying mechanisms driving HD, a synergistic treatment strategy that integrates various factors-such as distinct cell types, epigenetic patterns, genetic components, and methods to improve the cerebral microenvironment-may significantly enhance therapeutic outcomes. In the future, we eagerly anticipate ongoing innovations in interdisciplinary research that will bring profound advancements and refinements in the treatment of HD.
Huntington Disease/pathology* ; Humans ; Genetic Therapy/methods* ; Animals ; Huntingtin Protein/genetics* ; Cell- and Tissue-Based Therapy/methods*

OBJECTIVES: This study aims to explore the current status and risk factors of oral health-related quality of life OHRQoL in patients with mental disorders and provide evidence for effective intervention measures. METHODS: A total of 397 patients diagnosed with mental illness were selected by convenience sampling, and investigation was carried out using general data questionnaire, health literacy in dentistry-14 (HeLD-14), oral health impact profile-14 (OHIP-14), and oral health status checklist. RESULTS: The total score of OHIP-14 in patients with mental disorders was 8(2, 14). The score of HeLD-14 was negatively correlated with the score of OHIP-14 (r=-0.142, P<0.01). The results of multiple linear regression showed that six variables including annual family income, schizophrenia, sweets, frequency of visits to the dentist, dental caries, and missing teeth affected OHRQoL of patients with mental disorders (P<0.05). CONCLUSIONS The poor OHRQoL of psychiatric patients is associated with many factors. Medical personnel should pay attention to their oral health problems and develop targeted oral care programs throughout the course of disease to improve oral health and related quality of life of patients.
Humans ; Quality of Life ; Oral Health ; Mental Disorders ; Risk Factors ; Surveys and Questionnaires ; Male ; Female ; Dental Caries ; Adult ; Middle Aged ; Schizophrenia

Psychogenic non-epileptic seizures are accompanied by motor,behavioral,sensory,and/or cognitive changes,with the clinical manifestations similar to epileptic seizures.This disease is easy to be misdiagnosed and neglected in clinical work.At present,most intervention measures still depend on the experience of clinicians.This article reviews the comorbidities of psychogenic non-epileptic seizures,including mental and cognitive disorders,somatic syndrome,sleep disorders,and epilepsy.This review aims to strengthen the precision of clinical treatment and management of patients with psychogenic non-epileptic seizures and provide more efficient individualized diagnosis and treatment programs for patients.
Humans ; Seizures/diagnosis* ; Comorbidity ; Epilepsy ; Sleep Wake Disorders ; Mental Disorders ; Psychophysiologic Disorders ; Cognition Disorders

Objective To gain insights into the care service preferences and willingness of patients with severe mental disorders in Beijing,analyze the main factors affecting their participation in care services,and provide data support and decision-making reference for the optimal design of care services for patients with severe mental disorders and the improvement of relevant policies.Methods In July 2022,a questionnaire survey was conducted for a part of Beijing community patients with severe mental disorders selected by multi-stage stratified sampling,including the basic personal information and the preferences of discrete choice experiment.A mixed Logit model was used to perform regression analysis on the care service preferences,and the trade off between general and monetary attributes was quantified by willingness to pay(WTP).Results A total of 242 questionnaires were distributed,and 181 valid questionnaires were collected,with a response rate of 74.79%.The regression coefficients for the four attributes-service type,service content,service frequency,and service cost-all showed statistical significance(all P<0.05).Patients' most preferred attribute level was a service frequency covering about 90% of the time per month/year( β=1.059),while the least preferred was full-time residential care( β=-1.025).Increasing the service frequency from 30% to 90% corresponded to a WTP of 492.5 yuan,while changing the service type from home-based care to full-time residential care resulted in a WTP of -476.6 yuan.Moreover,there were differences in care service preferences and WTP among patient groups with different characteristics(all P<0.05).Conclusions Service type,service content,service frequency,and service cost all significantly affect the care service preferences of patients with severe mental disorders.There is heterogeneity in care service preferences among patient groups with different characteristics.
Humans ; Mental Disorders/therapy* ; Patient Preference ; Beijing ; Surveys and Questionnaires ; Male ; Female ; Choice Behavior ; Adult ; Middle Aged

OBJECTIVES: This study aims to describe the clinical characteristics, treatment received and outcome of patients diagnosed with HLH at the Philippine Children’s Medical Center from 2004 to 2017.

MATERIALS AND METHODS: This cross-sectional analytical study was conducted from June 10, 2023 to June 1, 2024 at the Philippine Children's Medical Center. Detailed information was obtained for each case according to protocol. A complete history was taken from the accompanying caretakers. Children aged 0 to 7 years and 11 months, recently diagnosed with focal epilepsy, were evaluated using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5-TR) criteria. The level of early child development was determined based on the total Battelle Developmental Inventory-2 developmental quotient score.

RESULTS: The study examined 246 children with focal epilepsy. Significant findings included those children with NDD had a higher median age (4.67 years) compared to those without NDD (3.37 years) (p < .001). A higher proportion of non-NDD children were under one year old. Children without NDD had mothers with higher educational attainment (p = .015) and came from families with higher incomes (p = .003). Neonatal complications such as hypoxic-ischemic encephalopathy (HIE) and sepsis were more common in children with NDD (p = .005 and p = .006). Phenobarbital use was more frequent in children with NDD (p = .001), who also had more abnormal EEG and neuroimaging findings (p < .001). Neurodevelopmental evaluations were conducted later for children with NDD (p < .001). A significant number (75.20%) of children exhibited neurodevelopmental problems, with global developmental delay being most prevalent. Crude analysis showed associations between age, number of antiseizure medications, and delays in evaluation with increased odds of NDD.

CONCLUSIONS: The study offers insights into children with focal epilepsy at a tertiary hospital in the Philippines, emphasizing the impact of low socioeconomic status, age, birth complications and multiple anti-seizure medications. These findings are vital for clinicians to modify care plans through a multidisciplinary approach to enhance outcomes and improve quality of life in this high-risk population.

Human ; Male ; Female ; Infant Newborn: First 28 Days After Birth ; Infant: 1-23 Months ; Child Preschool: 2-5 Yrs Old ; Child: 6-12 Yrs Old ; Neurodevelopmental Disorders ; Sepsis ; Hypoxia-ischemia, Brain ; Epilepsies, Partial ; Educational Status ; Diagnostic And Statistical Manual Of Mental Disorders ; Child Development

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused significant mental distress in populations globally. At the frontline of the pandemic, emergency departments (EDs) are the prime setting to observe the effects of the pandemic on the mental health of the population. We aimed to describe the trend of mental health-related ED attendances at an acute hospital in Singapore before and during the various stages of the COVID-19 pandemic. METHODS: This is a retrospective, descriptive study of patients who presented to the ED between 1 January 2019 and 31 December 2020. Patients diagnosed with mental health-related systematised nomenclature of medicine who visited the ED during this period were identified and were placed into mental health diagnosis categories for analysis. A comparison was made between patients who presented before the pandemic (2019) and during the pandemic (2020). RESULTS: During the study periods, we identified 1,421 patients, of whom 27 were excluded due to non-mental health-related diagnoses, leaving 1,394 patients for analysis. There was a 36.7% increase in mental health-related ED presentations from 2019 to 2020. The proportion of higher-acuity mental health-related ED attendances and number of suicide attempts also increased. CONCLUSION Our study described an increase in the proportion of high-acuity mental health-related ED attendances during the COVID-19 pandemic. Emergency physicians must be cognisant of the effects of the pandemic on mental health. Further research should be conducted to better equip the healthcare system for handling all aspects of the pandemic.
Humans ; COVID-19/psychology* ; Emergency Service, Hospital/statistics & numerical data* ; Retrospective Studies ; Singapore/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Mental Disorders/diagnosis* ; Mental Health ; SARS-CoV-2 ; Tertiary Care Centers ; Pandemics ; Aged ; Suicide, Attempted/statistics & numerical data* ; Young Adult ; Adolescent