The effect of living environment on developmental disorders in cold regions

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.

Role of brahma-related gene 1/brahma-associated factor subunits in neural stem/progenitor cells and related neural developmental disorders

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.

Evaluating Obesity Index among Children with Developmental Disorders

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.

Bibliographical Review on Rehabilitation of Executive Functions in Patients With Developmental Coordination Disorder(DCD)

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.

Efficacy of Children Neuropsychological and Behavioral Scale in Screening for Autism Spectrum Disorders through a Combination of Developmental Surveillance

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.

Prescription trends in children with pervasive developmental disorders:a claims data-based study in Japan

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.

PsyMuKB: An Integrative De Novo Variant Knowledge Base for Developmental Disorders

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.

Diagnosis of pervasive developmental disorders:when and how?An area-based study about health care providers

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.

3-Dimensional Kinematic Comparison of Arm Movements between an Individual with NGLY1 Deficiency and a Neurotypical Individual

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.

Current Evidence and Diverse Perspectives on Attention-Deficit/Hy­peractivity Disorder:A Systematic Review

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.

Clinical Characteristics, Cytogenetic and Molecular Findings in Patients with Disorders of Sex Development

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.

Identification of 1q21.1 microduplication in a family:A case report

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.

Socio-Cultural Representations and Therapeutic Itineraries of Parents of Autistic Children Followed in the INSP’s Children’s Mental Health Services

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.

Ultrastructure of focal cerebral cortex tissue from rats with focal cortical dysplasia

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.

Early Childhood Development (0 - 6 Years Old) from Healthy to Pathologic: A Review of the Literature

Early childhood development involves an appropriate global intervention concerning the different areas of development such as: physical, cognitive, language and socio-emotional [1]. Especially during the first six years of life in an adequate environment rich in exchange and interaction. We will present in this article a review of the literature concerning normal early childhood development, focus firstly in normal development’s steps, the importance of first experiences and first aid with a stable and caring attachment figure. second, we will describe the various developmental disorders, occurring during this age group which extends from birth to 6 years and based on the DSM5 classification, namely that developmental delay may concern only one aspect of development (e.g. language delay or motor delay specifically) or concern the different aspects of development (overall development delay). The dynamics of development is also important to clarify because schematically we contrast the pathologies fixed to progressive pathologies (where we find the concepts of stagnation or regression in the development of the child). We will discuss in the third chapter, the interest of early detection as well as the multiple clinical and psychometric diagnostic tools, which aim to detect any delay or disorder in order to initiate appropriate care and minimize the long-term consequences.

Validation and Translation of the Greek Version of the “DCDDaily-Q-GR” Questionnaire

The origin of Developmental Coordination Disorder (DCD) has not been clarified yet. DCD is considered as a movement disorder that may strongly affect child’s Activities of Daily Living (ADL). Reliable evaluation tools for young DCD are importantly useful. This study aimed to translate and validate the Developmental Coordination Disorder Daily Questionnaire (DCDDaily-Q) into Greek. The current validation study reports on the translation, cultural adaptation and validation of the Greek. The total sample consisted of 191 children (age 5 - 8 years) and their parents who completed the questionnaire as a reference group. The participants were randomly divided into two groups. The first group (100 parents) completed only the DCDDaily-Q. The second group consisted of 91 parents who completed the DCDDaily-Q, while their children were additionally evaluated with the Movement Assessment Battery for Children 2 (MABC-2). Then two groups were created that included (25) children with DCD and a control group 30 children with typical developmental. The results were analyzed was performed using IBM SPSS statistics 24.0 (a = 0.05). The internal consistency of the Greek version of the DCDDaily-Q was assessed (Cronbach’s α = 0.86). High test-retest reliability for all items and good diagnostic performance for identifying children with DCD were achieved with a sensitivity of 0.76 and a specificity of 0.67. The Greek version of DCDDaily-Q was proved to be a reliable and valid screening tool for ADL assessment in 5 to 8 year old children with DCD;offering an easy to use and economical tool in the Greek healthcare system.

Complete androgen insensitivity syndrome caused by the c.2678C>T mutation in the androgen receptor gene:A case report

BACKGROUND Androgen insensitivity syndrome is an X-linked recessive genetic disease caused by mutations in the androgen receptor gene(AR).However,the underlying molecular mechanisms for the majority of AR variants remain unclear.In this study,we identified a point variant in three patients with complete androgen insensitivity syndrome(CAIS),summarized the correlation analysis,and performed a literature review.CASE SUMMARY The proband was raised as a girl.In infancy,she was first referred to hospital with a right inguinal hernia.Ultrasonography revealed the absence of a uterus and ovaries,and a testis-like structure located at the inguinal canal.Further diagnostic workup detected a 46,XY karyotype,and fluorescence in situ hybridization analysis showed the presence of the SRY gene.Histological analysis revealed the excised tissue to be testicular.Twelve years later,she was admitted to our hospital with a lack of breast development.Her pubic hair and breasts were Tanner stage I.She had normal female external genitalia.Blood hormone tests showed normal testosterone levels,low estradiol levels,and high gonadotropin levels.Her two siblings underwent similar examinations,and all three had a rare hemizygous missense mutation in AR:c.2678C>T.In vitro functional analyses revealed decreased nuclear translocation in AR-c.2678C>T mutation cells.CONCLUSION This case of CAIS was caused by an AR variant(c.2678C>T).Functional studies showed impaired nuclear translocation ability of the mutant protein.

Factors influencing parent satisfaction with preventive health services for the early detection of speech and language delay in preschool children

The aim of this study was to identify parent and child characteristics which could influence parent satisfaction with preventive health services designed to detect preschool children with speech and language (SL) delay. This study was conducted on 101 children aged 18 to 36 months who participated in an organized SL delay early detection program. Validated instruments were used to assess children’s and parents’ characteristics. Satisfaction was evaluated using the client satisfaction questionnaire for the three activities of the program: 1) a public information session about SL development, 2) parent training sessions for parents concerned by their child SL development, and 3) a child’s SL assessment. Multiple logistic regressions were used to identify all independent factors (p < 0.05) associated with satisfaction and to estimate the odds ratios (OR) for satisfaction. Economically disadvantaged parents were less prone to participate in the first two activities of the early detection program. Older parents were more satisfied with the public information session (OR = 1.33 for 1 year increment;p = 0.001). Distressed parents were less satisfied with both the parent training sessions (OR = 0.28;p = 0.009) and the SL assessment (OR = 0.43;p = 0.046). Parents whose child had health problems at birth were less satisfied with the public information session (OR = 0.14, p = 0.03) and the SL assessment (OR = 0.33, p = 0.036). There is a need to better adapt the delivery of preventive services for the early detection of SL delay, especially for disadvantaged and distressed parents and for those whose child had suffered from health problems at birth.

Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development(DSD)patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1(NR5A1)gene.Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1.The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development.The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis.Microfluidic-based single-cell RNA sequencing(scRNA-seq)analysis found that the fibroblast cells were significantly increased(approximately 46.5%),whereas the number of main epididymal epithelial cells(approximately 9.2%),such as principal cells and basal cells,was dramatically decreased.Bioinformatics analysis of cell–cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition(EMT)process.The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.

Physical assessment and reference growth curves for children with 46,XY disorders of sex development

Importance:Impaired growth is an important factor in patients with disorders of sex development(DSD).Objective:To profile the growth of children with 46,XY DSD.Methods:We compared heights between 46,XY DSD children and normal boys and obtained growth curves for DSD using the k-median coefficient of variation method.The study subjects were categorized into groups with good response and poor response to the human chorionic gonadotrophin(HCG)test according to testosterone levels and were compared height standard deviation scores(HtSDS)with normal boys.Results:A total of 571 children with noncongenital adrenal hyperplasia(CAH)46,XY DSD were enrolled in this study.The overall HtSDS for the DSD subjects were 0.031 1.202.The HtSDS of DSD boys were lower than those for normal boys among multiple age groups since early infancy.In children aged≥12 years,the HtSDS values were significantly lower than the normal reference values for boys of the same age in both the good and poor response groups(P=.025 and P=.003,respectively).The HtSDS in the poor response group was generally lower than the normal reference value(P=.017).The average HtSDS values in the poor response groups were lower than those in the good response groups across multiple age groups.Interpretation:Growth retardation was evident in boys with non-CAH 46,XY DSD in early childhood and puberty.The level of growth retardation was related to testosterone level.DSD-specific growth curves can improve our understanding of growth dynamics and minimize the scope for bias in the assessment of growth in these children.