Developmental disorders(DDs)are a kind of chronic maladies,which can cause serious irreversible detriment to children’s physical and mental health.It is predominantly regulated by the interaction of environment and h...Developmental disorders(DDs)are a kind of chronic maladies,which can cause serious irreversible detriment to children’s physical and mental health.It is predominantly regulated by the interaction of environment and heredity.Cold regions are mainly located in the high latitudes of China.Their living environment is characterized by frequent cold wave,huge temperature difference,severe air pollution,high calorie diet,less exercise,smoking,drinking,etc.In recent years,substantial advances have been made in studies of the correlation between the living environment features in cold regions and the DDs.Accordingly,this article reviews the impact of the peculiar living environment of cold regions on DDs,with a view to provide fresh prevention strategies for reducing the morbidity of DDs in China cold regions by ameliorating living environment.展开更多
Different fates of neural stem/progenitor cells(NSPCs)and their progeny are determined by the gene regulatory network,where a chromatin-remodeling complex affects synergy with other regulators.Here,we review recent re...Different fates of neural stem/progenitor cells(NSPCs)and their progeny are determined by the gene regulatory network,where a chromatin-remodeling complex affects synergy with other regulators.Here,we review recent research progress indicating that the BRG1/BRM-associated factor(BAF)complex plays an important role in NSPCs during neural development and neural developmental disorders.Several studies based on animal models have shown that mutations in the BAF complex may cause abnormal neural differentiation,which can also lead to various diseases in humans.We discussed BAF complex subunits and their main characteristics in NSPCs.With advances in studies of human pluripotent stem cells and the feasibility of driving their differentiation into NSPCs,we can now investigate the role of the BAF complex in regulating the balance between self-renewal and differentiation of NSPCs.Considering recent progress in these research areas,we suggest that three approaches should be used in investigations in the near future.Sequencing of whole human exome and genome-wide association studies suggest that mutations in the subunits of the BAF complex are related to neurodevelopmental disorders.More insight into the mechanism of BAF complex regulation in NSPCs during neural cell fate decisions and neurodevelopment may help in exploiting new methods for clinical applications.展开更多
The prevalence of obesity not only among adults but also among children has been increasing globally. Furthermore, obese children reportedly go on to be obese in adulthood. Obesity is likely to cause lifestyle-related...The prevalence of obesity not only among adults but also among children has been increasing globally. Furthermore, obese children reportedly go on to be obese in adulthood. Obesity is likely to cause lifestyle-related diseases not only in able-bodied individuals but also in disabled children. Specific cognitive behavior observed in disabled children often hinders the provision of lifestyle guidance, such as nutritional and physical exercise instructions. To prevent such situations, early identification of obesity is required to improve lifestyle habits through diet and exercise in disabled children. This study included 285 children with developmental disorders. To assess a childhood obesity index, three obesity-related parameters were compared: the degree of obesity in school health, which has been used to evaluate the health of school children in Japan;abdominal circumference, which is useful for predicting visceral fat obesity;and the waist-to-height ratio (WHtR), which reflects visceral fat and physique. The abdominal circumference was significantly dependent on age. The degree of obesity and WHtR did not show a significant association with age. WHtR was significantly associated with the degree of obesity in school health. The WHtR is easily calculated as compared to the degree of index in school health which needs rather complicated calculations depending on age and age-specific coefficients. The study findings suggest that WHtR might be an easy-to-use obesity index comparable to the degree of obesity in school health in children with developmental disorders.展开更多
Background:The only drug approved for pervasive developmental disorders(PDD)in Japan is pimozide.Several psychotropic drugs are also prescribed for offlabel use in Japan,but details regarding their prescription and us...Background:The only drug approved for pervasive developmental disorders(PDD)in Japan is pimozide.Several psychotropic drugs are also prescribed for offlabel use in Japan,but details regarding their prescription and use are largely unknown.The purpose of this study was to clarify the use of drug treatment in Japanese children with PDD.Methods:Data were extracted from claims data from the Japan Medical Data Center for children younger than 18 years of age who were newly diagnosed with PDD(International Classification of Diseases version 10 codes:F84)from 2005 to 2010(total of 3276 patients as of 2010).The prescription rates were presented as the percentage of PDD patients who were prescribed each drug.Results:Prior to 2010,the prescription rates for atypical antipsychotics,other antipsychotics,psychostimulants,all other central nervous system drugs,anticovnvulsants,non-barbiturates,and Parkinson’s disease/syndrome drugs significantly increased among the Anatomical Therapeutic Chemical classifications defined as the“nervous system”(trend P≤0.02).The prescription rate for risperidone consistently increased,reaching 6.9%in 2010(trend P<0.0001),the highest rate of the surveyed drugs among the antipsychotics.The prescription rate for aripiprazole also increased(trend P<0.0001),reaching 1.9%in 2010.The prescription rate for pimozide showed no annual changes,with a low rate of 0.4%in 2010.Conclusion:Compared with pimozide,the prescription rates for risperidone,aripiprazole and other psychotropic drugs have increased.Because safety data for these drugs in Japanese children are sparse,there is a need for future safety evaluations of these drugs in Japanese children.展开更多
De novo variants(DNVs)are one of the most significant contributors to severe earlyonset genetic disorders such as autism spectrum disorder,intellectual disability,and other developmental and neuropsychiatric(DNP)disor...De novo variants(DNVs)are one of the most significant contributors to severe earlyonset genetic disorders such as autism spectrum disorder,intellectual disability,and other developmental and neuropsychiatric(DNP)disorders.Presently,a plethora of DNVs have been identified using next-generation sequencing,and many efforts have been made to understand their impact at the gene level.However,there has been little exploration of the effects at the isoform level.The brain contains a high level of alternative splicing and regulation,and exhibits a more divergent splicing program than other tissues.Therefore,it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders.To facilitate a better usage and improve the isoform-level interpretation of variants,we developed NeuroPsychiatric Mutation Knowledge Base(PsyMuKB).It contains a comprehensive,carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoformspecific mutations.PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations,such as expression,transcript genomic structures,protein interactions,and the mutation sites mapped on the protein structures.It also provides an easy-to-use web interface,allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms.PsyMuKB thus constitutes a valuable resource for identifying tissue-specific DNVs for further functional studies of related disorders.PsyMuKB is freely accessible at http://psymukb.net.展开更多
Objective This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016(CNBS-R2016)for Autism Spectrum Disorder(ASD)screening in the presence of developmental surveil...Objective This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016(CNBS-R2016)for Autism Spectrum Disorder(ASD)screening in the presence of developmental surveillance.Methods All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules(GDS).Spearman’s correlation coefficients and Kappa values were obtained.Taking GDS as a reference assessment,the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic(ROC)curves.The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule,Second Edition(ADOS-2).Results In total,150 children aged 12–42 months with ASD were enrolled.The developmental quotients of the CNBS-R2016 were correlated with those of the GDS(r=0.62–0.94).The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays(Kappa=0.73–0.89),except for Fine Motor.There was a significant difference between the proportions of Fine Motor,delays detected by the CNBS-R2016 and GDS(86.0%vs.77.3%).With GDS as a standard,the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor,which was 0.70.In addition,the positive rate of ASD was 100.0%and 93.5%when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used,respectively.Conclusion The CNBS-R2016 performed well in developmental assessment and screening for children with ASD,especially by Communication Warning Behaviors subscale.Therefore,the CNBS-R2016 is worthy of clinical application in children with ASD in China.展开更多
Background:Pervasive developmental disorders(PDDs)can be very difficult to diagnose in children and to communicate such a diagnosis to their parents.Families of children with PDD learn of their child's diagnosis l...Background:Pervasive developmental disorders(PDDs)can be very difficult to diagnose in children and to communicate such a diagnosis to their parents.Families of children with PDD learn of their child's diagnosis long after the first symptoms are noted in the child's behavior.Methods:An area-based survey was conducted to assess all social and health care providers taking care of patients with PDDs in the Veneto Region(North-East Italy).Results:Only 28%of health care providers arrived at a definite diagnosis when the child was in his/her first year of age,51%when the child was 2-3 years old and 21%from age of 4 years and up.On average,the latency between the time of the diagnosis and its communication to the family was 6.9 months.However,a number of families did not ever have a diagnosis communicated to them.Sometimes,68%of the providers did not communicate a PDDs diagnosis to patient's families,and 4%of them quite commonly.Conclusion:The well-known delay in making a diagnosis of PDDs has two distinct components:one relating to the difficulty of confirming a diagnosis of PDDs,the other,hitherto unrecognized,relating to the family being notified.展开更多
This study was conducted retrospectively on a cohort of 68 patients with steroid 5α-reductase 2(SRD5A2)deficiency and 46,XY disorders of sex development(DSD).Whole-exon sequencing revealed 28 variants of SRD5A2,and f...This study was conducted retrospectively on a cohort of 68 patients with steroid 5α-reductase 2(SRD5A2)deficiency and 46,XY disorders of sex development(DSD).Whole-exon sequencing revealed 28 variants of SRD5A2,and further analysis identified seven novel mutants.The preponderance of variants was observed in exon 1 and exon 4,specifically within the nicotinamide adenine dinucleotide phosphate(NADPH)-binding region.Among the entire cohort,53 patients underwent initial surgery at Sichuan Provincial People’s Hospital(Chengdu,China).The external genitalia scores(EGS)of these participants varied from 2.0 to 11.0,with a mean of 6.8(standard deviation[s.d.]:2.5).Thirty patients consented to hormone testing.Their average testosterone-todihydrotestosterone(T/DHT)ratio was 49.3(s.d.:23.4).Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome;and their T/DHT ratios were below the diagnostic threshold.Furthermore,assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants.These mechanisms include interference with NADPH binding(c.356G>C,c.365A>G,c.492C>G,and c.662T>G)and destabilization of the protein structure(c.727C>T).The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts.Seven novel variations were identified,and the variant database for the SRD5A2 gene was expanded.These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.展开更多
46,XY disorders of sex development(DSD)is characterized by incomplete masculinization genitalia,with gonadal dysplasia and with/without the presence of Mullerian structures.At least 30 genes related to 46,XY DSD have ...46,XY disorders of sex development(DSD)is characterized by incomplete masculinization genitalia,with gonadal dysplasia and with/without the presence of Mullerian structures.At least 30 genes related to 46,XY DSD have been found.However,the clinical phenotypes of patients with different gene mutations overlap,and accurate diagnosis relies on gene sequencing technology.Therefore,this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted nextgeneration sequencing(NGS)technology.Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital(Beijing,China).A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD.The incidence of these rare variants was approximately 69.0%(60/87).Twenty-five novel variants and 29 reported variants were identified.Based on the American College of Medical Genetics and Genomics(ACMG)guidelines,thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance.The overall diagnostic rate was about 42.5%based on the pathogenic and likely pathogenic variants.Androgen receptor{AR),steroid 5-alpha-reductase 2(SRD5A2)and nuclear receptor subfamily 5 Group A member 1(NR5A1)gene variants were identified in 21,13 and 13 patients,respectively.The incidence of these three gene variants was about 78.3%(47/60)in patients with rare variants.It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR,SRD5A2,and NR5A1 genes were the most common pathogenic genes in our cohort.展开更多
The clinical characteristics of patients with disorders of sex development（DSD）, and the diagnostic values of classic cytogenetic and molecular genetic assays for DSD were investigated. In the enrolled 56 cases, the...The clinical characteristics of patients with disorders of sex development（DSD）, and the diagnostic values of classic cytogenetic and molecular genetic assays for DSD were investigated. In the enrolled 56 cases, there were 9 cases of 46,XY DSD, 6 cases of Turner syndrome（TS）, one case of Super female syndrome, 25 cases of Klinefelter syndrome, 14 cases of 46,XX DSD, and one case of autosomal balanced rearrangements with hypospadias. The diagnosis of sex was made through physical examination, cytogenetic assay, ultrasonography, gonadal biopsy and hormonal analysis. PCR was used to detect SRY, ZFX, ZFY, DYZ3 and DYZ1 loci on Y and X chromosomes respectively. The DSD patients with the same category had similar clinical characteristics. The karyotypes in peripheral blood lymphocytes of all patients were identified. PCR-based analysis showed presence or absence of the X/Y-linked loci in several cases. Of the 9 cases of 46,XY DSD, 6 were positive for SRY, 9 for ZFX/ZFY, 9 for DYZ3 and 8 for DYZ1 loci. Of the 6 cases of TS, only 1 case with the karyotype of 45,X,/46,XX/46,XY was positive for all 5 loci. Of the 25 cases of Klinefelter syndrome, all were positive for all 5 loci. In one case of rare Klinefelter syndrome variants azoospermia factor（AZF） gene detection revealed the loss of the AZFa＋AZFb region. In 14 cases of 46,XX DSD, 7 cases were positive for SRY, 14 for ZFX, 7 for ZFY, 7 for ZYZ3, and 5 for DYZ1. PCR can complement and also confirm cytogenetic studies in the diagnosis of sex in cases of DSD.展开更多
The present study aims to establish a literature review on intervention programs for executive functions(EFs)through the use of fundamental motor skills,from a neuropsychopedagogical perspective in subjects with Devel...The present study aims to establish a literature review on intervention programs for executive functions(EFs)through the use of fundamental motor skills,from a neuropsychopedagogical perspective in subjects with Developmental Coordination Disorder(DCD).An exploratory study was carried out through an integrative literature review.The research was carried out in the Scientific databases Electronic Library Online(SciELO),Latin American and Caribbean Literature in Health Sciences(LILACS),Virtual Health Library-Psychology Brazil(BVSPSI),Electronic Journals of Psychology(PePSIC),in the periodicals available in the Brazilian Digital Library of Theses and Dissertations(BDTD)and on the website of the Coordination for the Improvement of Higher Education Personnel(CAPES).The covering publications took place from 2018 to 2023,14 articles were selected for analysis.This literature review made it possible to create strategies for stimulating EF and Visuomotor Functions so that educators and other professionals can better deal with students with DCD.It was perceived the need to carry out and develop more empirical research regarding the intervention of EFs and Visuomotor Functions by educators and professionals,with a greater sampling amplitude,to increase the number of studies that enable interventions both in children and in teenagers with DCD.展开更多
Hirschsprung’s disease (HSCR) is a developmental disorder characterized by the absence of ganglion cells in the distal colon, leading to functional obstruction. Bardet-Biedl syndrome (BBS) is a rare ciliopathy associ...Hirschsprung’s disease (HSCR) is a developmental disorder characterized by the absence of ganglion cells in the distal colon, leading to functional obstruction. Bardet-Biedl syndrome (BBS) is a rare ciliopathy associated with various clinical features, including HSCR. This review article aims to explore the underlying causes of HSCR in children with BBS, focusing on the genetic and developmental factors contributing to the pathogenesis of both conditions. We reviewed relevant literature, including peer-reviewed journal articles and case reports, to provide a comprehensive overview of the current understanding of the relationship between HSCR and BBS. Our findings highlight the complex interplay of genetic mutations, signaling pathways, and developmental processes involved in the pathogenesis of HSCR in BBS. Further research is needed to elucidate the precise mechanisms underlying this association and to develop targeted therapeutic strategies for children with HSCR and BBS.展开更多
BACKGROUND Copy number variation(CNV)has become widely recognized in recent years due to the extensive use of gene screening in developmental disorders and epilepsy research.1q21.1 microduplication syndrome is a rare ...BACKGROUND Copy number variation(CNV)has become widely recognized in recent years due to the extensive use of gene screening in developmental disorders and epilepsy research.1q21.1 microduplication syndrome is a rare CNV disease that can manifest as multiple congenital developmental disorders,autism spectrum disorders,congenital malformations,and congenital heart defects with genetic heterogeneity.CASE SUMMARY We reported a pediatric patient with 1q21.1 microduplication syndrome,and carried out a literature review to determine the correlation between 1q21.1microduplication and its phenotypes.We summarized the patient’s medical history and clinical symptoms,and extracted genomic DNA from the patient,her parents,elder brother,and sister.The patient was an 8-mo-old girl who was hospitalized for recurrent convulsions over a 2-mo period.Whole exon sequencing and whole genome low-depth sequencing(CNV-seq)were then performed.Whole exon sequencing detected a 1.58-Mb duplication in the CHR1:145883867-147465312 region,which was located in the 1q21.1 region.Family analysis showed that the pathogenetic duplication fragment,which was also detected in her elder brother’s DNA originated from the mother.CONCLUSION Whole exon sequencing combined with quantitative polymerase chain reaction can provide an accurate molecular diagnosis in children with 1q21.1 microduplication syndrome,which is of great significance for genetic counseling and early intervention.展开更多
Introduction:ADHD is one of the most common neurodevelopmental disorders in childhood and adolescence.Although the disorder starts to manifest early in childhood,a significant proportion of cases often persists into a...Introduction:ADHD is one of the most common neurodevelopmental disorders in childhood and adolescence.Although the disorder starts to manifest early in childhood,a significant proportion of cases often persists into adulthood.ADHD negatively and significantly impacts social and occupational functioning and academic performance.A number of extant theories and scientific evidence provide insight into the genesis and manifestations of ADHD and the attendant challenges of significant dysfunction that individuals may encounter at home,school,and the workplace.Method:This systematic review was conducted through a literature search for published peer-reviewed articles using standard PRISMA guidelines.The goal of the study was to explore current theories,models,concepts,and risk factors about ADHD published in peer-reviewed literature.We made use of use several online databases-including PsycINFO,PubMed,Web of Science,ScienceDirect,and Medline in the process of searching for relevant studies.Relevant peer-reviewed publications since the 1980s when the term Attention-Deficit/Hyperactivity Disorder(ADHD)was introduced in DSM-III-R were included.Non-peer-reviewed publications,including dissertations,editorials,commentaries,and materials published in languages other than English were excluded.Results and Discussion:The results of the review indicated that ADHD is characterized by a behavioral reaction that interferes with personal and social functioning.The factors associated with ADHD fall into several major thematic areas,including genetic and hereditary factors;dietary and nutritional factors;parenting and behavioral factors;adverse early life events,and high-risk environmental factors,crystallized by a number of developmental and behavioral theories.The review also identified a number of extant models and theories that attempt to explain the diverse perspectives associated with ADHD.Conclusions:This study has attempted to identify the major risk factors and diverse models and theories associated with ADHD.The thematic risk factors include genetic and hereditary factors;dietary and nutritional factors;parenting and behavioral factors;adverse early life events,and high-risk environmental factors.The most prominent models identified include the biomedical model and the bio-psycho-social models,the latter being a more holistic approach which aims to treat both the patient and the disease.This review would provide an additional evidence base to individuals,families,and educators to make informed choices and decisions in the best interest of the affected children,including their personal growth,healthcare,and medical needs,academic performance,and social skills development.展开更多
Pervasive developmental disorders (PDD) remain little known to populations in developing countries. In black Africa their social representations remain strongly influenced by local belief systems. The general objectiv...Pervasive developmental disorders (PDD) remain little known to populations in developing countries. In black Africa their social representations remain strongly influenced by local belief systems. The general objective of this study was to understand the perceptions and representations of Ivorian parents vis-à-vis PDD. This was a mixed (qualitative and quantitative) prospective cross-sectional study with a descriptive aim that involved a sample of 49 parents. The sampling was of the qualitative type by multiple cases with reasoned choice by saturation. Our results showed that male parents were mostly aged between 40 - 49 years (48.98%) with a higher level of education (67.34%) while mothers were mostly aged between 30 - 39 (61.22%) and a higher level (30.61%). Autistic children were negatively perceived by their parents: either as a source of psychological suffering (82.85%), or as mysterious children who sacrificed their parents (44.66%), or as “bobo” children (mute children in common Ivorian language) (16.66%) or like rude children (13.34%). The supposed origin of the disorder according to the parents was mystical-religious (60.94%);natural (25%);hereditary (6.25%). In 6.25% of cases, PDD were assumed to be of unknown or iatrogenic origin attributable to vaccination (1.56%). 75.51% of parents said that in addition to conventional medical therapies, they also used traditional therapies. The use of this therapeutic alternative would be linked to the perceptions and beliefs that feed the socio-cultural representations of our respondents.展开更多
NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems ...NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems with tear formation. Movements are hyperkinetic and may include dysmetric, choreo-athetoid, myoclonic and dystonic movement elements. To date, there have been no quantitative reports describing arm movements of individuals with NGLY1 Deficiency. This report provides quantitative information about a series of arm movements performed by an individual with NGLY1 Deficiency and an aged-matched neurotypical participant. Three categories of arm movements were tested: 1) open ended reaches without specific end point targets;2) goal-directed reaches that included grasping an object;3) picking up small objects from a table placed in front of the participants. Arm movement kinematics were obtained with a camera-based motion analysis system and “initiation” and “maintenance” phases were identified for each movement. The combination of the two phases was labeled as a “complete” movement. Three-dimensional analysis techniques were used to quantify the movements and included hand trajectory pathlength, joint motion area, as well as hand trajectory and joint jerk cost. These techniques were required to fully characterize the movements because the NGLY1 individual was unable to perform movements only in the primary plane of progression instead producing motion across all three planes of movement. The individual with NGLY1 Deficiency was unable to pick up objects from a table or effectively complete movements requiring crossing the midline. The successfully completed movements were analyzed using the above techniques and the results of the two participants were compared statistically. Almost all comparisons revealed significant differences between the two participants, with a notable exception of the 3D initiation area as a percentage of the complete movement. The statistical tests of these measures revealed no significant differences between the two participants, possibly suggesting a common underlying motor control strategy. The 3D techniques used in this report effectively characterized arm movements of an individual with NGLY1 deficiency and can be used to provide information to evaluate the effectiveness of genetic, pharmacological, or physical rehabilitation therapies.展开更多
Fibroblast growth factor 8(FGF8),a secreted signaling molecule,involves in regulating cell survival,proliferation,migration,and differentiation.It exhibits a highly dynamic gene expression pattern throughout embryonic...Fibroblast growth factor 8(FGF8),a secreted signaling molecule,involves in regulating cell survival,proliferation,migration,and differentiation.It exhibits a highly dynamic gene expression pattern throughout embryonic development,participates in craniofacial structures,limbs,internal organs,brain development,and is crucial during organogenesis.The dysregulation of precise localization and dosage of FGF8 at distinct embryonic stages can lead to developmental multiorgan abnormalities.This comprehensive review explores the FGF8 expression in humans and mice,summarizes the involvement of FGF8 in various tissues including craniofacial,limbs,cardiovascular and urogenital system,nephrogenesis,lung,and brain development as well as developmental abnormalities resulting from the aberrant regulations of FGF8 such as skeletal abnormalities,ciliopathies,and holoprosencephaly.展开更多
Forty-six XX disorder of sex development is an uncommon medical condition observed at times during the evaluation of a man＇s fertility. The following is a case series and literature review of phenotypically normal me...Forty-six XX disorder of sex development is an uncommon medical condition observed at times during the evaluation of a man＇s fertility. The following is a case series and literature review of phenotypically normal men diagnosed with this karyotype. Our goal is to comprehend the patients＇ clinical presentation as well as their laboratory results aiming to explore options available for their management. A formal literature review through PubMed and MEDLINE databases was performed using ＂46 XX man＂ as a word search. A total of 55 patients, including those conveyed in this article were diagnosed with a 46 XX karyotype during their fertility evaluation. The patients＇ mean age _＋ s.d. was 34 ＋ 10 years and their mean height ＋ s.d. was 166 ＋ 6.5 cm. Overall, they presented with hypergonadotropic hypogonadism. Sexual dysfunction, reduced hair distribution, and gynecomastia were reported in 20% （4120）, 25.8% （8/31）, and 42% （13131） of the patients, respectively. The SRYgene was detected in 36 （83.7%） and was absent in the remaining seven （16.3%） patients. We found that a multidisciplinary approach to management is preferred in 46 XX patients. Screening for remnants of the mullerian ducts and for malignant transformation in dysgenetic gonads is imperative. Hypogonadism should be addressed, while fertility options are in vitro fertilization with donor sperm or adoption.展开更多
Androgen insensitivity syndrome （AIS）, an X-linked recessive genetic disorder of sex development, is caused by mutations in the androgen receptor （AR） gene, and is characterized by partial or complete inability of...Androgen insensitivity syndrome （AIS）, an X-linked recessive genetic disorder of sex development, is caused by mutations in the androgen receptor （AR） gene, and is characterized by partial or complete inability of specific tissues to respond to androgens in individuals with the 46,XY karyotype. This study aimed to investigate AR gene mutations and to characterize genotype-phenotype correlations. Ten patients from unrelated families, aged 2-31 years, were recruited in the study. Based on karyotype, altered hormone profile, and clinical manifestations, nine patients were preliminarily diagnosed with complete AIS and one with partial AIS. Genetic analysis of AR gene revealed the existence of 10 different mutations, of which five were novel （c.2112 C〉G[p.STO4R], c.2290T〉A[p.Y764N], c.2626C〉T[p.Q876X], c.933dupC[p.K313Qfs＊28], and c.1067delC[p.A356Efs＊123]）; the other five were previously reported （c.1789G〉A[p.A597T], c.2566C〉T[p.R856C], c.2668G〉A[p.V890M], c.2679C〉T[p.P893L], and c.1605C〉G[p.Y535X]）. Regarding the distribution of these mutations, 60.0% were clustered in the ligand-binding domain of AR gene. Exons 1 and 8 of AR gene each accounted for 30.0% （3/10） of all mutations. Most of the truncation mutations were in exon 1 and missense mutations were mainly located in exons 4-8. Our study expands the spectrum of AR gene mutations and confirms the usefulness of AR gene sequencing to support a diagnosis of AIS and to enable prenatal or antenatal screening.展开更多
BACKGROUND： Developing a model of focal cortical dysplasia in microgyrus and observing the ultrastructure of focal tissue is of important significance for analyzing the pathology of cortical developmental disorder an...BACKGROUND： Developing a model of focal cortical dysplasia in microgyrus and observing the ultrastructure of focal tissue is of important significance for analyzing the pathology of cortical developmental disorder and the factors of structural changes. OBJECTIVE： This study was to observe the pathological characteristics of focal tissue around the microgyrus of rats with cortical developmental disorder using an electron microscope, so as to analyze the causes associated with cerebral cortical developmental disorder. DESIGN： A randomized controlled animal experiment. SETTING： The First Affiliated Hospital of Chongqing Medical University. MATERIALS： This study was carried out in the Chongqing Key Laboratory of Neurology, Room for Electron Microscope of Chongqing Medical University, and Laboratory Animal Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University of Chinese PLA between January 2004 and August 2006. Eighteen healthy newborn male Wistar rats, weighing 3.0 - 6.0 g, provided by the Laboratory Animal Center, Daping Hospital, Third Military Medical University of Chinese PLA, were involved in this study. The protocol was carried out in accordance with animal ethics guidelines for the use and care of animals. Probes （Chongqing Wire ＆ Cable Factory, China） were made of copper core wire with diameter of 1mm. METHODS： The rats were randomly divided into 3 groups with 6 in each： normal control group, liquid nitrogen injured group and sham-operation group. （1）In the liquid nitrogen injured group, a blunt probe frozen by liquid nitrogen was placed on fronto-parietal crinial bone of rats for 8 s. A 3 - 5 cm of microgyrus was induced in the unilateral cerebral sensory cortical area. In the sham-operation group, probe was placed at the room temperature. In the normal control group, rats were untouched. （2） The conscious state and electrical activity of brain of rats in each group were observed. （3） 2 - 3 mm thickness of hippocampal tissue with coronary section was taken for observing its ultrastructure under a transmission electron microscope. MAIN OUTCOME MEASURES： （1） The ultrastructure of hippocampal tissue. （2）The conscious state and electrical activity of brain of rats. RESULTS： Eighteen rats were enrolled in the final analysis. （1） Observation of hippocampal ultrastructure： Electromicroscopic pathological findings showed that for each rat of the liquid nitrogen injured group, mitochondrium in the pyramidal neuron around the microgyrus was swelled, endoplasmic reticulum was expanded, glial cells were swelled, water gathered around the blood capillary, partial medullary sheath was degenerated, neuropilem was normal and no obviously abnormal synapse was found. （2） Changes in conscious state of rats： Rats in the normal control group and sham-operation group had no convulsive seizure, but those in the liquid nitrogen injured group had occasionally. Most of them showed increased activities, excitation and restlessness, scratching and frequent ＂ watching face-like activities＂. （3）Electrical activity of brain of rats： Electroencephalogram recording of liquid nitrogen injured group showed that small wave amplitude of rhythm took the main part. No typical sharp wave, V wave, sharp and slow wave, V and slow waves were discharged. CONCLUSION： Liquid nitrogen can lead to cerebral cortical developmental disorder. Pathological changes of ultrastructure of focal tissue around the microgyrus can provide pathological basis for epilepsy associated with focal cortical developmental disorder.展开更多
基金This work was supported by the Key Project of Harbin Medical University Cultivation Fund.
文摘Developmental disorders(DDs)are a kind of chronic maladies,which can cause serious irreversible detriment to children’s physical and mental health.It is predominantly regulated by the interaction of environment and heredity.Cold regions are mainly located in the high latitudes of China.Their living environment is characterized by frequent cold wave,huge temperature difference,severe air pollution,high calorie diet,less exercise,smoking,drinking,etc.In recent years,substantial advances have been made in studies of the correlation between the living environment features in cold regions and the DDs.Accordingly,this article reviews the impact of the peculiar living environment of cold regions on DDs,with a view to provide fresh prevention strategies for reducing the morbidity of DDs in China cold regions by ameliorating living environment.
基金Supported by the Natural Science Foundation of Anhui Province,No.2008085MH251Key Research and Development Project of Anhui Province,No.202004J07020037+1 种基金Anhui Provincial Institute of Translational Medicine,No.2021zhyx-C19National Undergraduate Innovation and Entrepreneurship training program,No.202010366016。
文摘Different fates of neural stem/progenitor cells(NSPCs)and their progeny are determined by the gene regulatory network,where a chromatin-remodeling complex affects synergy with other regulators.Here,we review recent research progress indicating that the BRG1/BRM-associated factor(BAF)complex plays an important role in NSPCs during neural development and neural developmental disorders.Several studies based on animal models have shown that mutations in the BAF complex may cause abnormal neural differentiation,which can also lead to various diseases in humans.We discussed BAF complex subunits and their main characteristics in NSPCs.With advances in studies of human pluripotent stem cells and the feasibility of driving their differentiation into NSPCs,we can now investigate the role of the BAF complex in regulating the balance between self-renewal and differentiation of NSPCs.Considering recent progress in these research areas,we suggest that three approaches should be used in investigations in the near future.Sequencing of whole human exome and genome-wide association studies suggest that mutations in the subunits of the BAF complex are related to neurodevelopmental disorders.More insight into the mechanism of BAF complex regulation in NSPCs during neural cell fate decisions and neurodevelopment may help in exploiting new methods for clinical applications.
文摘The prevalence of obesity not only among adults but also among children has been increasing globally. Furthermore, obese children reportedly go on to be obese in adulthood. Obesity is likely to cause lifestyle-related diseases not only in able-bodied individuals but also in disabled children. Specific cognitive behavior observed in disabled children often hinders the provision of lifestyle guidance, such as nutritional and physical exercise instructions. To prevent such situations, early identification of obesity is required to improve lifestyle habits through diet and exercise in disabled children. This study included 285 children with developmental disorders. To assess a childhood obesity index, three obesity-related parameters were compared: the degree of obesity in school health, which has been used to evaluate the health of school children in Japan;abdominal circumference, which is useful for predicting visceral fat obesity;and the waist-to-height ratio (WHtR), which reflects visceral fat and physique. The abdominal circumference was significantly dependent on age. The degree of obesity and WHtR did not show a significant association with age. WHtR was significantly associated with the degree of obesity in school health. The WHtR is easily calculated as compared to the degree of index in school health which needs rather complicated calculations depending on age and age-specific coefficients. The study findings suggest that WHtR might be an easy-to-use obesity index comparable to the degree of obesity in school health in children with developmental disorders.
基金supported by a grant from the Ministry of Health,Labour and Welfare(MHLW)of Japan(H24-iyaku-wakate-011)
文摘Background:The only drug approved for pervasive developmental disorders(PDD)in Japan is pimozide.Several psychotropic drugs are also prescribed for offlabel use in Japan,but details regarding their prescription and use are largely unknown.The purpose of this study was to clarify the use of drug treatment in Japanese children with PDD.Methods:Data were extracted from claims data from the Japan Medical Data Center for children younger than 18 years of age who were newly diagnosed with PDD(International Classification of Diseases version 10 codes:F84)from 2005 to 2010(total of 3276 patients as of 2010).The prescription rates were presented as the percentage of PDD patients who were prescribed each drug.Results:Prior to 2010,the prescription rates for atypical antipsychotics,other antipsychotics,psychostimulants,all other central nervous system drugs,anticovnvulsants,non-barbiturates,and Parkinson’s disease/syndrome drugs significantly increased among the Anatomical Therapeutic Chemical classifications defined as the“nervous system”(trend P≤0.02).The prescription rate for risperidone consistently increased,reaching 6.9%in 2010(trend P<0.0001),the highest rate of the surveyed drugs among the antipsychotics.The prescription rate for aripiprazole also increased(trend P<0.0001),reaching 1.9%in 2010.The prescription rate for pimozide showed no annual changes,with a low rate of 0.4%in 2010.Conclusion:Compared with pimozide,the prescription rates for risperidone,aripiprazole and other psychotropic drugs have increased.Because safety data for these drugs in Japanese children are sparse,there is a need for future safety evaluations of these drugs in Japanese children.
基金supported by grants from the National Key R&D Program of China(Grant No.2017YFC0909200)the National Natural Science Foundation of China(Grant Nos.81671328 and 61802057)+3 种基金Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(Grant No.1610000043)Innovation Research Plan supported by Shanghai Municipal Education Commission(Grant No.ZXWF082101)Science and Technology Development Plan of Jilin Province(Grant Nos.20180414006GH and 20180520028JH)the Fundamental Research Funds for the Central Universities
文摘De novo variants(DNVs)are one of the most significant contributors to severe earlyonset genetic disorders such as autism spectrum disorder,intellectual disability,and other developmental and neuropsychiatric(DNP)disorders.Presently,a plethora of DNVs have been identified using next-generation sequencing,and many efforts have been made to understand their impact at the gene level.However,there has been little exploration of the effects at the isoform level.The brain contains a high level of alternative splicing and regulation,and exhibits a more divergent splicing program than other tissues.Therefore,it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders.To facilitate a better usage and improve the isoform-level interpretation of variants,we developed NeuroPsychiatric Mutation Knowledge Base(PsyMuKB).It contains a comprehensive,carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoformspecific mutations.PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations,such as expression,transcript genomic structures,protein interactions,and the mutation sites mapped on the protein structures.It also provides an easy-to-use web interface,allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms.PsyMuKB thus constitutes a valuable resource for identifying tissue-specific DNVs for further functional studies of related disorders.PsyMuKB is freely accessible at http://psymukb.net.
基金This study was supported by Emergency Technology Research Project of Huazhong University of Science and Technology(No.2020kfyXGYJ020).
文摘Objective This study aimed to explore the clinical value of Children Neuropsychological and Behavioral Scale-Revision 2016(CNBS-R2016)for Autism Spectrum Disorder(ASD)screening in the presence of developmental surveillance.Methods All participants were evaluated by the CNBS-R2016 and Gesell Developmental Schedules(GDS).Spearman’s correlation coefficients and Kappa values were obtained.Taking GDS as a reference assessment,the performance of the CNBS-R2016 for detecting the developmental delays of children with ASD was analyzed with receiver operating characteristic(ROC)curves.The efficacy of the CNBS-R2016 to screen for ASD was explored by comparing Communication Warning Behavior with Autism Diagnostic Observation Schedule,Second Edition(ADOS-2).Results In total,150 children aged 12–42 months with ASD were enrolled.The developmental quotients of the CNBS-R2016 were correlated with those of the GDS(r=0.62–0.94).The CNBS-R2016 and GDS had good diagnostic agreement for developmental delays(Kappa=0.73–0.89),except for Fine Motor.There was a significant difference between the proportions of Fine Motor,delays detected by the CNBS-R2016 and GDS(86.0%vs.77.3%).With GDS as a standard,the areas under the ROC curves of the CNBS-R2016 were above 0.95 for all the domains except Fine Motor,which was 0.70.In addition,the positive rate of ASD was 100.0%and 93.5%when the cut-off points of 7 and 12 in the Communication Warning Behavior subscale were used,respectively.Conclusion The CNBS-R2016 performed well in developmental assessment and screening for children with ASD,especially by Communication Warning Behaviors subscale.Therefore,the CNBS-R2016 is worthy of clinical application in children with ASD in China.
基金supported by the Veneto Region Health Administration
文摘Background:Pervasive developmental disorders(PDDs)can be very difficult to diagnose in children and to communicate such a diagnosis to their parents.Families of children with PDD learn of their child's diagnosis long after the first symptoms are noted in the child's behavior.Methods:An area-based survey was conducted to assess all social and health care providers taking care of patients with PDDs in the Veneto Region(North-East Italy).Results:Only 28%of health care providers arrived at a definite diagnosis when the child was in his/her first year of age,51%when the child was 2-3 years old and 21%from age of 4 years and up.On average,the latency between the time of the diagnosis and its communication to the family was 6.9 months.However,a number of families did not ever have a diagnosis communicated to them.Sometimes,68%of the providers did not communicate a PDDs diagnosis to patient's families,and 4%of them quite commonly.Conclusion:The well-known delay in making a diagnosis of PDDs has two distinct components:one relating to the difficulty of confirming a diagnosis of PDDs,the other,hitherto unrecognized,relating to the family being notified.
基金supported by the Sichuan Science and Technology Program(No.2022JDZH0029 to JYY)the Special Fund for Clinical Research and Translational Medicine from Chinese Academy of Medical Sciences(No.2022-I2M-C&T-B-117 to JYY)the Sichuan Key Research and Development Project from the Department of Science and Technology of Sichuan Province(No.2022YFS0237 to YMT).
文摘This study was conducted retrospectively on a cohort of 68 patients with steroid 5α-reductase 2(SRD5A2)deficiency and 46,XY disorders of sex development(DSD).Whole-exon sequencing revealed 28 variants of SRD5A2,and further analysis identified seven novel mutants.The preponderance of variants was observed in exon 1 and exon 4,specifically within the nicotinamide adenine dinucleotide phosphate(NADPH)-binding region.Among the entire cohort,53 patients underwent initial surgery at Sichuan Provincial People’s Hospital(Chengdu,China).The external genitalia scores(EGS)of these participants varied from 2.0 to 11.0,with a mean of 6.8(standard deviation[s.d.]:2.5).Thirty patients consented to hormone testing.Their average testosterone-todihydrotestosterone(T/DHT)ratio was 49.3(s.d.:23.4).Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome;and their T/DHT ratios were below the diagnostic threshold.Furthermore,assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants.These mechanisms include interference with NADPH binding(c.356G>C,c.365A>G,c.492C>G,and c.662T>G)and destabilization of the protein structure(c.727C>T).The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts.Seven novel variations were identified,and the variant database for the SRD5A2 gene was expanded.These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
基金This work was supported by the National Natural Science Foundation of China(No.81971375 and No.81771576)the National Key Research and Development Program of China(2016YFC0905100)+1 种基金the CAMS Innovation Fund for Medical Sciences(2016-I2M-1-002)the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences(No.2017PT32020 and No.2018PT32001).
文摘46,XY disorders of sex development(DSD)is characterized by incomplete masculinization genitalia,with gonadal dysplasia and with/without the presence of Mullerian structures.At least 30 genes related to 46,XY DSD have been found.However,the clinical phenotypes of patients with different gene mutations overlap,and accurate diagnosis relies on gene sequencing technology.Therefore,this study aims to determine the prevalence of pathogenic mutations in a Chinese cohort with 46,XY DSD by the targeted nextgeneration sequencing(NGS)technology.Eighty-seven 46,XY DSD patients were enrolled from the Peking Union Medical College Hospital(Beijing,China).A total of fifty-four rare variants were identified in 60 patients with 46,XY DSD.The incidence of these rare variants was approximately 69.0%(60/87).Twenty-five novel variants and 29 reported variants were identified.Based on the American College of Medical Genetics and Genomics(ACMG)guidelines,thirty-three variants were classified as pathogenic or likely pathogenic variants and 21 variants were assessed as variants of uncertain significance.The overall diagnostic rate was about 42.5%based on the pathogenic and likely pathogenic variants.Androgen receptor{AR),steroid 5-alpha-reductase 2(SRD5A2)and nuclear receptor subfamily 5 Group A member 1(NR5A1)gene variants were identified in 21,13 and 13 patients,respectively.The incidence of these three gene variants was about 78.3%(47/60)in patients with rare variants.It is concluded that targeted NGS is an effective method to detect pathogenic mutations in 46,XY DSD patients and AR,SRD5A2,and NR5A1 genes were the most common pathogenic genes in our cohort.
文摘The clinical characteristics of patients with disorders of sex development（DSD）, and the diagnostic values of classic cytogenetic and molecular genetic assays for DSD were investigated. In the enrolled 56 cases, there were 9 cases of 46,XY DSD, 6 cases of Turner syndrome（TS）, one case of Super female syndrome, 25 cases of Klinefelter syndrome, 14 cases of 46,XX DSD, and one case of autosomal balanced rearrangements with hypospadias. The diagnosis of sex was made through physical examination, cytogenetic assay, ultrasonography, gonadal biopsy and hormonal analysis. PCR was used to detect SRY, ZFX, ZFY, DYZ3 and DYZ1 loci on Y and X chromosomes respectively. The DSD patients with the same category had similar clinical characteristics. The karyotypes in peripheral blood lymphocytes of all patients were identified. PCR-based analysis showed presence or absence of the X/Y-linked loci in several cases. Of the 9 cases of 46,XY DSD, 6 were positive for SRY, 9 for ZFX/ZFY, 9 for DYZ3 and 8 for DYZ1 loci. Of the 6 cases of TS, only 1 case with the karyotype of 45,X,/46,XX/46,XY was positive for all 5 loci. Of the 25 cases of Klinefelter syndrome, all were positive for all 5 loci. In one case of rare Klinefelter syndrome variants azoospermia factor（AZF） gene detection revealed the loss of the AZFa＋AZFb region. In 14 cases of 46,XX DSD, 7 cases were positive for SRY, 14 for ZFX, 7 for ZFY, 7 for ZYZ3, and 5 for DYZ1. PCR can complement and also confirm cytogenetic studies in the diagnosis of sex in cases of DSD.
文摘The present study aims to establish a literature review on intervention programs for executive functions(EFs)through the use of fundamental motor skills,from a neuropsychopedagogical perspective in subjects with Developmental Coordination Disorder(DCD).An exploratory study was carried out through an integrative literature review.The research was carried out in the Scientific databases Electronic Library Online(SciELO),Latin American and Caribbean Literature in Health Sciences(LILACS),Virtual Health Library-Psychology Brazil(BVSPSI),Electronic Journals of Psychology(PePSIC),in the periodicals available in the Brazilian Digital Library of Theses and Dissertations(BDTD)and on the website of the Coordination for the Improvement of Higher Education Personnel(CAPES).The covering publications took place from 2018 to 2023,14 articles were selected for analysis.This literature review made it possible to create strategies for stimulating EF and Visuomotor Functions so that educators and other professionals can better deal with students with DCD.It was perceived the need to carry out and develop more empirical research regarding the intervention of EFs and Visuomotor Functions by educators and professionals,with a greater sampling amplitude,to increase the number of studies that enable interventions both in children and in teenagers with DCD.
文摘Hirschsprung’s disease (HSCR) is a developmental disorder characterized by the absence of ganglion cells in the distal colon, leading to functional obstruction. Bardet-Biedl syndrome (BBS) is a rare ciliopathy associated with various clinical features, including HSCR. This review article aims to explore the underlying causes of HSCR in children with BBS, focusing on the genetic and developmental factors contributing to the pathogenesis of both conditions. We reviewed relevant literature, including peer-reviewed journal articles and case reports, to provide a comprehensive overview of the current understanding of the relationship between HSCR and BBS. Our findings highlight the complex interplay of genetic mutations, signaling pathways, and developmental processes involved in the pathogenesis of HSCR in BBS. Further research is needed to elucidate the precise mechanisms underlying this association and to develop targeted therapeutic strategies for children with HSCR and BBS.
文摘BACKGROUND Copy number variation(CNV)has become widely recognized in recent years due to the extensive use of gene screening in developmental disorders and epilepsy research.1q21.1 microduplication syndrome is a rare CNV disease that can manifest as multiple congenital developmental disorders,autism spectrum disorders,congenital malformations,and congenital heart defects with genetic heterogeneity.CASE SUMMARY We reported a pediatric patient with 1q21.1 microduplication syndrome,and carried out a literature review to determine the correlation between 1q21.1microduplication and its phenotypes.We summarized the patient’s medical history and clinical symptoms,and extracted genomic DNA from the patient,her parents,elder brother,and sister.The patient was an 8-mo-old girl who was hospitalized for recurrent convulsions over a 2-mo period.Whole exon sequencing and whole genome low-depth sequencing(CNV-seq)were then performed.Whole exon sequencing detected a 1.58-Mb duplication in the CHR1:145883867-147465312 region,which was located in the 1q21.1 region.Family analysis showed that the pathogenetic duplication fragment,which was also detected in her elder brother’s DNA originated from the mother.CONCLUSION Whole exon sequencing combined with quantitative polymerase chain reaction can provide an accurate molecular diagnosis in children with 1q21.1 microduplication syndrome,which is of great significance for genetic counseling and early intervention.
文摘Introduction:ADHD is one of the most common neurodevelopmental disorders in childhood and adolescence.Although the disorder starts to manifest early in childhood,a significant proportion of cases often persists into adulthood.ADHD negatively and significantly impacts social and occupational functioning and academic performance.A number of extant theories and scientific evidence provide insight into the genesis and manifestations of ADHD and the attendant challenges of significant dysfunction that individuals may encounter at home,school,and the workplace.Method:This systematic review was conducted through a literature search for published peer-reviewed articles using standard PRISMA guidelines.The goal of the study was to explore current theories,models,concepts,and risk factors about ADHD published in peer-reviewed literature.We made use of use several online databases-including PsycINFO,PubMed,Web of Science,ScienceDirect,and Medline in the process of searching for relevant studies.Relevant peer-reviewed publications since the 1980s when the term Attention-Deficit/Hyperactivity Disorder(ADHD)was introduced in DSM-III-R were included.Non-peer-reviewed publications,including dissertations,editorials,commentaries,and materials published in languages other than English were excluded.Results and Discussion:The results of the review indicated that ADHD is characterized by a behavioral reaction that interferes with personal and social functioning.The factors associated with ADHD fall into several major thematic areas,including genetic and hereditary factors;dietary and nutritional factors;parenting and behavioral factors;adverse early life events,and high-risk environmental factors,crystallized by a number of developmental and behavioral theories.The review also identified a number of extant models and theories that attempt to explain the diverse perspectives associated with ADHD.Conclusions:This study has attempted to identify the major risk factors and diverse models and theories associated with ADHD.The thematic risk factors include genetic and hereditary factors;dietary and nutritional factors;parenting and behavioral factors;adverse early life events,and high-risk environmental factors.The most prominent models identified include the biomedical model and the bio-psycho-social models,the latter being a more holistic approach which aims to treat both the patient and the disease.This review would provide an additional evidence base to individuals,families,and educators to make informed choices and decisions in the best interest of the affected children,including their personal growth,healthcare,and medical needs,academic performance,and social skills development.
文摘Pervasive developmental disorders (PDD) remain little known to populations in developing countries. In black Africa their social representations remain strongly influenced by local belief systems. The general objective of this study was to understand the perceptions and representations of Ivorian parents vis-à-vis PDD. This was a mixed (qualitative and quantitative) prospective cross-sectional study with a descriptive aim that involved a sample of 49 parents. The sampling was of the qualitative type by multiple cases with reasoned choice by saturation. Our results showed that male parents were mostly aged between 40 - 49 years (48.98%) with a higher level of education (67.34%) while mothers were mostly aged between 30 - 39 (61.22%) and a higher level (30.61%). Autistic children were negatively perceived by their parents: either as a source of psychological suffering (82.85%), or as mysterious children who sacrificed their parents (44.66%), or as “bobo” children (mute children in common Ivorian language) (16.66%) or like rude children (13.34%). The supposed origin of the disorder according to the parents was mystical-religious (60.94%);natural (25%);hereditary (6.25%). In 6.25% of cases, PDD were assumed to be of unknown or iatrogenic origin attributable to vaccination (1.56%). 75.51% of parents said that in addition to conventional medical therapies, they also used traditional therapies. The use of this therapeutic alternative would be linked to the perceptions and beliefs that feed the socio-cultural representations of our respondents.
文摘NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems with tear formation. Movements are hyperkinetic and may include dysmetric, choreo-athetoid, myoclonic and dystonic movement elements. To date, there have been no quantitative reports describing arm movements of individuals with NGLY1 Deficiency. This report provides quantitative information about a series of arm movements performed by an individual with NGLY1 Deficiency and an aged-matched neurotypical participant. Three categories of arm movements were tested: 1) open ended reaches without specific end point targets;2) goal-directed reaches that included grasping an object;3) picking up small objects from a table placed in front of the participants. Arm movement kinematics were obtained with a camera-based motion analysis system and “initiation” and “maintenance” phases were identified for each movement. The combination of the two phases was labeled as a “complete” movement. Three-dimensional analysis techniques were used to quantify the movements and included hand trajectory pathlength, joint motion area, as well as hand trajectory and joint jerk cost. These techniques were required to fully characterize the movements because the NGLY1 individual was unable to perform movements only in the primary plane of progression instead producing motion across all three planes of movement. The individual with NGLY1 Deficiency was unable to pick up objects from a table or effectively complete movements requiring crossing the midline. The successfully completed movements were analyzed using the above techniques and the results of the two participants were compared statistically. Almost all comparisons revealed significant differences between the two participants, with a notable exception of the 3D initiation area as a percentage of the complete movement. The statistical tests of these measures revealed no significant differences between the two participants, possibly suggesting a common underlying motor control strategy. The 3D techniques used in this report effectively characterized arm movements of an individual with NGLY1 deficiency and can be used to provide information to evaluate the effectiveness of genetic, pharmacological, or physical rehabilitation therapies.
基金supported by the National Natural Science Foundation of China(No.81701350,31671252)Health Technology Plan of Zhejiang Province(No.2023RC205)The Natural Science Foundation of Zhejiang Province(No.LQ22C120002).
文摘Fibroblast growth factor 8(FGF8),a secreted signaling molecule,involves in regulating cell survival,proliferation,migration,and differentiation.It exhibits a highly dynamic gene expression pattern throughout embryonic development,participates in craniofacial structures,limbs,internal organs,brain development,and is crucial during organogenesis.The dysregulation of precise localization and dosage of FGF8 at distinct embryonic stages can lead to developmental multiorgan abnormalities.This comprehensive review explores the FGF8 expression in humans and mice,summarizes the involvement of FGF8 in various tissues including craniofacial,limbs,cardiovascular and urogenital system,nephrogenesis,lung,and brain development as well as developmental abnormalities resulting from the aberrant regulations of FGF8 such as skeletal abnormalities,ciliopathies,and holoprosencephaly.
文摘Forty-six XX disorder of sex development is an uncommon medical condition observed at times during the evaluation of a man＇s fertility. The following is a case series and literature review of phenotypically normal men diagnosed with this karyotype. Our goal is to comprehend the patients＇ clinical presentation as well as their laboratory results aiming to explore options available for their management. A formal literature review through PubMed and MEDLINE databases was performed using ＂46 XX man＂ as a word search. A total of 55 patients, including those conveyed in this article were diagnosed with a 46 XX karyotype during their fertility evaluation. The patients＇ mean age _＋ s.d. was 34 ＋ 10 years and their mean height ＋ s.d. was 166 ＋ 6.5 cm. Overall, they presented with hypergonadotropic hypogonadism. Sexual dysfunction, reduced hair distribution, and gynecomastia were reported in 20% （4120）, 25.8% （8/31）, and 42% （13131） of the patients, respectively. The SRYgene was detected in 36 （83.7%） and was absent in the remaining seven （16.3%） patients. We found that a multidisciplinary approach to management is preferred in 46 XX patients. Screening for remnants of the mullerian ducts and for malignant transformation in dysgenetic gonads is imperative. Hypogonadism should be addressed, while fertility options are in vitro fertilization with donor sperm or adoption.
基金The authors are grateful to the patients and their family members for participating in this study. This study was supported by grants from the National Natural Science Foundation of China （81771645 and 81471432 to YQT）.
文摘Androgen insensitivity syndrome （AIS）, an X-linked recessive genetic disorder of sex development, is caused by mutations in the androgen receptor （AR） gene, and is characterized by partial or complete inability of specific tissues to respond to androgens in individuals with the 46,XY karyotype. This study aimed to investigate AR gene mutations and to characterize genotype-phenotype correlations. Ten patients from unrelated families, aged 2-31 years, were recruited in the study. Based on karyotype, altered hormone profile, and clinical manifestations, nine patients were preliminarily diagnosed with complete AIS and one with partial AIS. Genetic analysis of AR gene revealed the existence of 10 different mutations, of which five were novel （c.2112 C〉G[p.STO4R], c.2290T〉A[p.Y764N], c.2626C〉T[p.Q876X], c.933dupC[p.K313Qfs＊28], and c.1067delC[p.A356Efs＊123]）; the other five were previously reported （c.1789G〉A[p.A597T], c.2566C〉T[p.R856C], c.2668G〉A[p.V890M], c.2679C〉T[p.P893L], and c.1605C〉G[p.Y535X]）. Regarding the distribution of these mutations, 60.0% were clustered in the ligand-binding domain of AR gene. Exons 1 and 8 of AR gene each accounted for 30.0% （3/10） of all mutations. Most of the truncation mutations were in exon 1 and missense mutations were mainly located in exons 4-8. Our study expands the spectrum of AR gene mutations and confirms the usefulness of AR gene sequencing to support a diagnosis of AIS and to enable prenatal or antenatal screening.
基金the National Natural Science Foundation of China, No. 30570636a Grant from Applied Basic Research of Committee of Education of Chongqing, No.2001-12-29Medical Science and Technology Foundation of Chongqing City, No. 01-1-013
文摘BACKGROUND： Developing a model of focal cortical dysplasia in microgyrus and observing the ultrastructure of focal tissue is of important significance for analyzing the pathology of cortical developmental disorder and the factors of structural changes. OBJECTIVE： This study was to observe the pathological characteristics of focal tissue around the microgyrus of rats with cortical developmental disorder using an electron microscope, so as to analyze the causes associated with cerebral cortical developmental disorder. DESIGN： A randomized controlled animal experiment. SETTING： The First Affiliated Hospital of Chongqing Medical University. MATERIALS： This study was carried out in the Chongqing Key Laboratory of Neurology, Room for Electron Microscope of Chongqing Medical University, and Laboratory Animal Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University of Chinese PLA between January 2004 and August 2006. Eighteen healthy newborn male Wistar rats, weighing 3.0 - 6.0 g, provided by the Laboratory Animal Center, Daping Hospital, Third Military Medical University of Chinese PLA, were involved in this study. The protocol was carried out in accordance with animal ethics guidelines for the use and care of animals. Probes （Chongqing Wire ＆ Cable Factory, China） were made of copper core wire with diameter of 1mm. METHODS： The rats were randomly divided into 3 groups with 6 in each： normal control group, liquid nitrogen injured group and sham-operation group. （1）In the liquid nitrogen injured group, a blunt probe frozen by liquid nitrogen was placed on fronto-parietal crinial bone of rats for 8 s. A 3 - 5 cm of microgyrus was induced in the unilateral cerebral sensory cortical area. In the sham-operation group, probe was placed at the room temperature. In the normal control group, rats were untouched. （2） The conscious state and electrical activity of brain of rats in each group were observed. （3） 2 - 3 mm thickness of hippocampal tissue with coronary section was taken for observing its ultrastructure under a transmission electron microscope. MAIN OUTCOME MEASURES： （1） The ultrastructure of hippocampal tissue. （2）The conscious state and electrical activity of brain of rats. RESULTS： Eighteen rats were enrolled in the final analysis. （1） Observation of hippocampal ultrastructure： Electromicroscopic pathological findings showed that for each rat of the liquid nitrogen injured group, mitochondrium in the pyramidal neuron around the microgyrus was swelled, endoplasmic reticulum was expanded, glial cells were swelled, water gathered around the blood capillary, partial medullary sheath was degenerated, neuropilem was normal and no obviously abnormal synapse was found. （2） Changes in conscious state of rats： Rats in the normal control group and sham-operation group had no convulsive seizure, but those in the liquid nitrogen injured group had occasionally. Most of them showed increased activities, excitation and restlessness, scratching and frequent ＂ watching face-like activities＂. （3）Electrical activity of brain of rats： Electroencephalogram recording of liquid nitrogen injured group showed that small wave amplitude of rhythm took the main part. No typical sharp wave, V wave, sharp and slow wave, V and slow waves were discharged. CONCLUSION： Liquid nitrogen can lead to cerebral cortical developmental disorder. Pathological changes of ultrastructure of focal tissue around the microgyrus can provide pathological basis for epilepsy associated with focal cortical developmental disorder.
