BACKGROUND Visual impairment during early childhood can hinder motor,language,and social development,yet data on its developmental impact across common pediatric ocular diseases remain limited.AIM To investigate the d...BACKGROUND Visual impairment during early childhood can hinder motor,language,and social development,yet data on its developmental impact across common pediatric ocular diseases remain limited.AIM To investigate the developmental impact of low vision and blindness on children under six with common ocular diseases.METHODS This retrospective study reviewed records of new patients under six with visual impairment at Siriraj Hospital’s low vision rehabilitation center(January 2017-October 2022).We collected ocular,systemic,and developmental data;recorded visual acuity in the better-seeing eye after refractive correction;and assessed developmental domains with the DenverⅡ.Univariable and multi-variable logistic regression identified factors associated with developmental delay.RESULTS A total of 161 pediatric patients(mean age 24.9±18.9 months)were enrolled and evaluated based on their ability to fix on and follow an object or light source.Some were further assessed using the Allen picture chart and all had visual acuity worse than 1.07±0.58 LogMAR,and 83.2%were identified as having global developmental delay(GDD).The three most common ocular causes were cortical visual impairment(CVI),optic neuropathy/atrophy,and optic nerve hypoplasia.Extremely poor visual acuity(inability to fixate and follow)was significantly associated with GDD[adjusted odds ratio(AOR)41.0]and delays in all developmental domains:Gross motor(AOR 10.0),fine motor(AOR 12.8),language(AOR 5.3),and personal-social skills(AOR 13.4)(P≤0.002).Multiple disabilities,most often visual impairment with cerebral palsy,were also significantly associated with gross motor delays(AOR 7.7)and fine motor delays(AOR 4.0)(P<0.05).CVI was also related to delays in language and personal-social skills(AOR 9.1 each)(P<0.05).CONCLUSION This study underscores the developmental issues in children with visual impairment,especially those with poorer acuity,CVI,and multiple disabilities.Significant delays were observed in all domains,including GDD.A timely referral to specialists is strongly recommended.展开更多
BACKGROUND Unintended pregnancy occurs when an individual or couple conceives without planning or desire,which can potentially affect a child’s physical,mental,and social well-being.This can then lead to long-term so...BACKGROUND Unintended pregnancy occurs when an individual or couple conceives without planning or desire,which can potentially affect a child’s physical,mental,and social well-being.This can then lead to long-term socioeconomic challenges for families and communities.Although its impact on child growth and development is a pressing concern,research remains limited particularly in multicenter settings.AIM To examine the long-term consequences of unintended pregnancy on the critical years of early childhood growth and development.METHODS This analytical observational study employed a case-control design and was conducted in research centers across Indonesia,encompassing those located in Central Java,Lampung,Bali,and West Nusa Tenggara.A total of 700 children aged≤5 years with histories of intended or unintended pregnancies participated.Data collection involved structured interviews and direct anthropometric and developmental assessments.Data analyses were conducted using multivariate statistics and partial least squares structural equation modeling.RESULTS Unintended pregnancy was found to have a statistically significant effect on both child growth(t=8.178;P<0.001)and child development(t=25.688;P<0.001).Key growth problems identified included underweight,undernutrition,abnormal head circumference,and stunting.Developmental challenges prominently associated with unintended pregnancy included behavioral and emotional disorders,autism spectrum disorder,attentiondeficit/hyperactivity disorder,social and motor skill deficits,as well as visual and hearing impairments.CONCLUSION Unintended pregnancy significantly affects child growth and development,underscoring the need for early intervention,quality prenatal care,and strengthened family planning policies.展开更多
BACKGROUND Xia–Gibbs syndrome(XGS,OMIM:615829),caused by mutations within the ATHook DNA-binding motif-containing protein 1(AHDC1)gene(OMIM:615790),located on the short arm of chromosome 1 within the cytogenetic band...BACKGROUND Xia–Gibbs syndrome(XGS,OMIM:615829),caused by mutations within the ATHook DNA-binding motif-containing protein 1(AHDC1)gene(OMIM:615790),located on the short arm of chromosome 1 within the cytogenetic band 1p36.11,contains five noncoding 5 exons,a single 4.9-kb coding exon,and a noncoding 3 exon.CASE SUMMARY In this case report,we diagnosed and treated a 6-mo-old girl with XGS.The primary clinical symptoms included global developmental delay,hypotonia,and mild dysmorphic features.Using high-throughput whole-exosome sequencing to sequence the patient and her parents,and the results showed a novel frameshift mutation of c.1155dupG(p.Arg386Alafs*3)in the AHDC1 gene.The paternal gene was wild type.CONCLUSION This report extends the mutation spectrum of the AHDC1 gene to provide the diagnostic basis for genetic counseling in families with XGS.展开更多
<strong>Background:</strong> Childhood cataract causing visual impairment can compound developmental delay (DD) if left untreated. Current literature in children with DD is limited;thus, we evaluated catar...<strong>Background:</strong> Childhood cataract causing visual impairment can compound developmental delay (DD) if left untreated. Current literature in children with DD is limited;thus, we evaluated cataract etiology, challenges, and treatment compliance in this group. <strong>Purpose:</strong> To report the presentation and challenges associated with cataract management in children with developmental delay (DD) at a tertiary care pediatric hospital. <strong>Methods:</strong> Retrospective review of 100 patients (173 eyes) presenting with cataracts and DD from February 2014 to December 2017. <strong>Results:</strong> 100 patients (173 eyes) were included. 27 patients had unilateral cataracts and 73 bilateral. The average age was 120.55 months (SD 63.77, range 5.87 - 243.16);the average follow-up period was 57.7 months (SD 139.14, range 1.03 - 1412.30). 61% of patients (55% eyes) underwent medical management for cataracts due to: cataract was not visually significant (66% eyes), parent deferred surgery (11% eyes), self-abusive behavior (14% eyes), and medical conditions that limited visual recovery (9% eyes). 32% of patients were unable to perform objective visual acuity by age 5. Patients with self-abusive behavior were more likely to present with or develop retinal detachment (RD) (35%) compared to those without self-abusive behavior (6%) (p = 0.0028). A statistically significant difference in the difficulty of examination (p < 0.0001) and poor compliance of glasses wear (p < 0.0001) was found in nonverbal patients. Surgical complications occurred in 39% of eyes. Those with intraocular lens placement after cataract extraction were more likely to develop visual axis opacification (27% eyes) than those who remained aphakic (9% eyes) (p = 0.0313). <strong>Conclusion:</strong> Cataract extraction in pediatric patients with DD can be associated with success, however, providers should prepare for limitations in managing these patients.展开更多
The objective of this original pilot study was to determine if the Drums Alive<span style="white-space:nowrap;"><sup>®</sup></span> Kids Beats intervention could provide stati...The objective of this original pilot study was to determine if the Drums Alive<span style="white-space:nowrap;"><sup>®</sup></span> Kids Beats intervention could provide statistically significant improvements to physical and motor skill performance on participants with Developmental Delays (DD) using the Dusseldorf Motor-Proficiency-Test for children (MOT 4-6) model. The researchers selected the research-based Drums Alive Kids Beat intervention because of its multidisciplinary methodology that in previous studies demonstrated positive effects on physiological, psychological, neurological, educational, rhythmical, and socio-emotional literacy. Facilitators used standardized Drums Alive approved lesson plans and equipment to conduct the intervention through a battery of music, movement and drumming-centered exercises and activities. The 30 participants were German students between 4.9 and 10.2 years of age, without any inclusion or exclusion characteristics, who were divided into three groups consisting of two intervention groups: IG Kindergarten (IG Kinder), IG Elementary<span style="font-family:;" "=""><span style="font-family:Verdana;"> (IG Elem) with varied physical, social, and emotional DD that affected gross and fine motor skills, movement, coordination, and behavioral control;and, a Control Group (CG) that had normal physical and motor skill development (</span><b><span style="font-family:Verdana;">Table 1</span></b><span style="font-family:Verdana;">). The results of the study suggested that the Drums Alive Kids Beats intervention provided statistically significant improvements in physical and motor skill performance in children with DD, namely, 24% improvement (IG Kinder), 14% (IG Elem) vice a minor 4% improvement (CG). Of note, during this study to measure physical capability pre- and post-intervention, the facilitators noticed significant improvements in behavior in both IG groups;therefore, they chose to conduct a collateral study to measure six behavioral domains which will be documented in a future publication to demonstrate the exclusive relationship between the Drums Alive Kids Beats intervention and improvement in behavior.</span></span>展开更多
Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiatio...Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation. WTK1 cells contain a p53 mutation, whereas the TK6 cell line has the native p53 tumor-suppressor gene. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. Using probes that target specific regions on chromosomes associated with a distinct subset of microdeletions and microduplications either established or thought to be responsible for intellectual disability or developmental delay, we have demonstrated that WTK1 and TK6 are not impacted in the same way by irradiation. Instead, each cell line presents its own unique MLPA profile. The most notable differences are the appearance of nine unique probe signals only seen in WTK1 cells. These results are important in the study of how different cell lines can be affected in significantly different ways depending on the presence or absence of wild type p53.展开更多
BACKGROUND Autism spectrum disorders(ASD)represent a substantial social problem affecting at least 1 in 100 children worldwide.These conditions are very often accompanied by intellectual disability(ID)and speech delay...BACKGROUND Autism spectrum disorders(ASD)represent a substantial social problem affecting at least 1 in 100 children worldwide.These conditions are very often accompanied by intellectual disability(ID)and speech delay;thus,they can be considered within a clinical continuum of neurodevelopmental disorders.Given the high heterogeneity of ASD,the subjective nature of diagnostic criteria,and the presence of phenocopies,identifying genetic determinants of these disorders remains a challenge.AIM To investigate the spectrum and frequency of rare genetic variants in genes with proven association with ASD in Russian children.METHODS 110 patients from 106 families were recruited into the study mean age at diagnosis 6 years;boy-to-girl ratio 3:1.Most of the patients(84%)demonstrated a combination of ASD with developmental delay(DD)or ID.Patients with syndromic features were subjected to the chromosomal microarray analysis.The remained children underwent clinical exome sequencing aimed at identifying presumably monogenic causes of ASD.The study focused on rare(minor allele frequency≤0.001)variants affecting high-confidence ASD-associated genes.RESULTS Pathogenic copy number variations were detected in three(7%)of the patients examined.Clinical exome sequencing revealed pathogenic/likely pathogenic variants in 12 of 105 cases(11%),indicating the presence of monogenic syndromes with established clinical significance(Pitt-Hopkins syndrome,ZTTK syndrome,syndromic X-linked ID of Billuart type,Snijders-Blok-Campeau,Helsmoortel-van der Aa,Coffin-Siris,Clark-Baraitser,Keefstra syndromes,etc.).In addition,27 patients(26%)had 37 rare variants of unknown clinical significance in DSCAM,SHANK2,AUTS2,ADNP,ANKRD11,APBA2,ARID1B,ASTN2,ATRX,SCN1A,CHD2,DEAF1,EHMT1,GRIN2B,NBEA,NR4A2,TRIO,TRIP12,POGZ,EP300,FOXP1,PCDH19,GRIN2A,NCKAP1,and CHD8 genes.No specific variant was detected more than once in unrelated patients.Among the genes with rare variants found in 2 or more patients were TRIP12(n=4),AUTS2(n=3),ARID1B(n=3),PCDH19(n=3),EP300(n=3),TRIO(n=2),ASTN2(n=2),EHMT1(n=2),and CHD2(n=2).Of note,5 male ASD/DD patients from 3 unrelated families had PCDH19 missense variants,confirming that at least some hemizygous males with non-mosaic PCDH19 variants may present with neurobehavioral abnormalities.These variants did not cause epilepsy restricted to females in patients’mothers or sisters.CONCLUSION These data confirm a tremendous diversity of genetic causes of ASD.Clinical exome sequencing may serve as a reasonable alternative to whole-exome sequencing.展开更多
The article published in World Journalof Pediatrics entitled as"Introducing PRIDE:Development and Validation of a Developmental Delay Screening Tool in a Community Population"by Wu et al.[1]presents an innov...The article published in World Journalof Pediatrics entitled as"Introducing PRIDE:Development and Validation of a Developmental Delay Screening Tool in a Community Population"by Wu et al.[1]presents an innovative use of item response theory to develop and validate the Parent-Reported Indicator of Developmental Evaluation for Chinese Children(PRIDE)tool.展开更多
Cortical malformations,including focal cortical dysplasia type II(FCDII),are a common cause of drug-resistant epilepsy and developmental delay.Consideration of surgery has become the standard of care for those patient...Cortical malformations,including focal cortical dysplasia type II(FCDII),are a common cause of drug-resistant epilepsy and developmental delay.Consideration of surgery has become the standard of care for those patients.However,10%-50% of patients with FCD experience post-surgical relapses[1],and many do not even qualify as surgical candidates.Effective treatments for FCD-associated epilepsy are lacking.展开更多
Global developmental delay/intellectual disability(GDD/ID)with a prevalence of 1%e3%represents one of the biggest medical and social challenges in our society.^(1)Genetic factors are the main causes of GDD/ID and earl...Global developmental delay/intellectual disability(GDD/ID)with a prevalence of 1%e3%represents one of the biggest medical and social challenges in our society.^(1)Genetic factors are the main causes of GDD/ID and early diagnosis is crucial to improving the prognosis of GDD/ID children.^(2)Chromosomal microarray analysis,as a first-tier clinical test,^(3)remains limited because of the insufficient to detect small variations while whole exome sequencing(WES)can detect both single-nucleotide variants(SNVs)and copy-number variants(CNVs),effectively improving the diagnostic yield of GDD/ID.展开更多
BACKGROUND Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities(NECRC)is a rare,autosomal,dominant neurological disorder caused by mutations in the ZMYM2 gene.To date,the clinical and...BACKGROUND Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities(NECRC)is a rare,autosomal,dominant neurological disorder caused by mutations in the ZMYM2 gene.To date,the clinical and functional characteristics of the novel ZMYM2 mutation c.2090_2091del have not yet been reported.CASE SUMMARY The patient was an 18.5-mo-old Chinese boy with motor and language delay,microcephaly,facial dysmorphism,moderate malnutrition,single palmar crease on the left hand,synpolydactyly of the right foot,hypotonia and feeding problems.The boy who was diagnosed with NECRC was enrolled in the First Affiliated Hospital,Henan University of Chinese Medicine,and his clinical data were collected.From the whole-exon sequencing(WES)data,the pathogenic SNVs/InDels were identified,and the molecular findings were characterized.WES revealed that the heterozygous variant in the ZMYM2 gene was c.2090_20-91del,p.Ser697TrpfsTer3,a frameshift mutation,which is a NECRC-related gene mutation.CONCLUSION We performed a systematic literature review to identify and characterize NECRC.Substantial evidence from the literature indicated that patients with ZMYM2 gene mutation showed different degrees of intellectual disability,motor and language retardation,facial dysmorphism,and a few had congenital heart defects,kidney and urinary tract abnormalities.Early diagnosis and prompt management with comprehensive rehabilitation training are beneficial,but may not improve long-term outcomes.展开更多
Objective: to explore the characteristics and clinical significance of cranial MRI in children with mental retardation/comprehensive developmental retardation (ID/GDD) caused by genetic factors. Methods: a retrospecti...Objective: to explore the characteristics and clinical significance of cranial MRI in children with mental retardation/comprehensive developmental retardation (ID/GDD) caused by genetic factors. Methods: a retrospective study was conducted to analyze the cranial MRI of 51 children eligible for inclusion. Results: 8 cases (15.69%) had extra-cerebral space widening, 16 cases (31.37%) had abnormal ventricular system, 13 cases (25.49%) had abnormal white matter myelination, 6 cases (11.76%) had abnormal cerebral cortex development, 15 cases (29.41%) had abnormal corpus callosum development, 7 cases (13.73%) had abnormal cerebellum development, 10 cases (19.61%) had other or special abnormalities, 12 cases (23.53%) had no abnormality, 24 cases (47.06%) had multiple abnormalities. Conclusion: cranial MRI is of great significance in the etiological diagnosis of ID/GDD and can assist in the selection of genetic testing methods.展开更多
Importance:Understanding the significance of motor skills in promoting physical fitness(PF)can offer valuable insights for devising comprehensive intervention and clinical rehabilitation programs for children with glo...Importance:Understanding the significance of motor skills in promoting physical fitness(PF)can offer valuable insights for devising comprehensive intervention and clinical rehabilitation programs for children with global developmental delay(GDD).However,it remains unclear whether fundamental motor skills(FMS)can improve the PF of children with GDD.Objective:To investigate the correlation between FMS and PF in children with GDD.Methods:A total of 180 children with GDD and 180 typically developing(TD)children aged 3-5 years were selected.All participants completed the Gesell Developmental Schedule,FMS,and PF tests at Beijing Children’s Hospital between September 2022 and August 2023.Partial correlation and regression analyses were performed to examine the relationship between FMS and PF.Results:Children with GDD had significantly lower FMS and PF scores compared to TD children(P<0.05).No significant differences were found between males and females with GDD in FMS and PF score(P>0.05).A more severe developmental delay was associated with lower FMS and PF scores.The correlation coefficients between individual FMS items and individual PF items,as well as the total PF score,ranged from 0.20 to 0.56.Regression analysis indicated that manual dexterity(β=0.241,P=0.029)and body balance(β=0.399,P=0.001)significantly predicted the total PF score.Interpretation:In children with GDD,both FMS and PF are underdeveloped.Focusing on motor skills development is vital for promoting their PF.展开更多
45X/46XY mosaicism is a rare chromosome disease. The apparent prevalence of males and females with 45X/46XY is 5.6 and 2.1 per 100,000 liveborn males and females. We present a boy who had a developmental delay with hy...45X/46XY mosaicism is a rare chromosome disease. The apparent prevalence of males and females with 45X/46XY is 5.6 and 2.1 per 100,000 liveborn males and females. We present a boy who had a developmental delay with hypospadias. He was referred to pediatric genetics and was diagnosed with 45X/46XY mosaicism by peripheral blood chromosome examination. During serial rehabilitation programs, his speech delay was caught up. But his poor attention and hyperactivity are obvious progressively. We should pay attention to these patients, not only physical conditions but also psychological problems.展开更多
Recurrent genomic imbalances at 16p 11.2 are genetic risk factors of variable penetrance for developmental delay and autism.Recently, 16pl 1.2（chr16：29.5 Mb-30.1 Mb） deletion has also been detected in individuals w...Recurrent genomic imbalances at 16p 11.2 are genetic risk factors of variable penetrance for developmental delay and autism.Recently, 16pl 1.2（chr16：29.5 Mb-30.1 Mb） deletion has also been detected in individuals with early-onset severe obesity.The penetrance of 16p11.2 deletion as a genetic risk factor for obesity is unknown.We evaluated the growth and body mass characteristics of 28 individuals with 16p11.2 （chr16：29.5 Mb-30.1 Mb） deletion originally ascertained for their developmental disorders by reviewing their medical records.We found that nine individuals could be classified as obese and six as overweight.These individuals generally had early feeding and growth difficulties,and started to gain excessive weight around 5-6 years of age.Thirteen out of the 18 deletion carriers aged 5 years and older（72%） were overweight or obese,whereas only two of 10 deletion carriers（20%） younger than five were overweight or obese.Males exhibited more severe obesity than females.Thus,the obesity phenotype of 16p11.2 deletion carriers is of juvenile onset,exhibited an age- and gender-dependent penetrance. 16p11.2 deletion appears to predispose individuals to juvenile onset obesity and in this case are similar to the well-described Prader-Willi syndrome（PWS）.Early detection of this deletion will provide opportunity to prevent obesity.展开更多
BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report...BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report a case of a 13-year-old Chinese boy with lifelong global developmental delay,speech and language delay,and intellectual disabilities.He had short stature and irregular dentition,but no other abnormal clinical findings.A de novo heterozygous nonsense point mutation was detected by genetic analysis in exon 6 of SATB2,c.687C>A(p.Y229X)(NCBI reference sequence:NM_001172509.2),and neither of his parents had the mutation.This mutation is the first reported and was evaluated as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics.SAS was diagnosed,and special education performed.Our report of a SAS case in China caused by a SATB2 mutation expanded the genotype options for the disease.The heterogeneous manifestations can be induced by complicated pathogenic involvements and functions of SATB2 from reviewed literatures:(1)SATB2 haploinsufficiency;(2)the interference of truncated SATB2 protein to wild-type SATB2;and(3)different numerous genes regulated by SATB2 in brain and skeletal development in different developmental stages.CONCLUSION Global developmental delays are usually the initial presentations,and the diagnosis was challenging before other presentations occurred.Regular follow-up and genetic analysis can help to diagnose SAS early.Verification for genes affected by SATB2 mutations for heterogeneous manifestations may help to clarify the possible pathogenesis of SAS in the future.展开更多
Importance:The process of brain development in children with developmental delay is not well known.Amide proton transfer-weighted(APTw)imaging is a novel molecular magnetic resonance imaging(MRI)technique that can non...Importance:The process of brain development in children with developmental delay is not well known.Amide proton transfer-weighted(APTw)imaging is a novel molecular magnetic resonance imaging(MRI)technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process,and may be useful for providing insights into brain development.Objective:To assess the contribution of amide proton transfer-weighted(APTw)imaging and magnetization transfer(MT)imaging to the evaluation of children with developmental delay(DD).Methods:Fifty-one patients with DD were recruited to this study.The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging(MRI).Thirty patients(10 girls,20 boys;age range:1-8 months;median age:4 months)in group A showed delayed myelination on MRI,while 21 patients(3 girls,18 boys;age range:12-36months;median age:25months)in group B showed normal myelination on MRI.Fifty-one age-and sex-matched children with normal developmental quotient(DQ)and normal MRI appearance were recruited as normal controls.Three-slice APTw/MT axial imaging was performed at the level of the centrum semiovale,the basal ganglia and the pons.Quantitative data of the MT ratio(MTR)and APTw were analyzed for multiple brain regions.Independent-samplet-tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls.Analysis of Covariance was conducted to correct the statistical results.The level of statistical significance was set toP<0.05.Results:For group A,the MTR values were lower in all regions(P=0.004-0.033)compared with the normal controls,while the APTw values were higher in the pons,middle cerebellar peduncle,corpus callosum,frontal white matter,occipital white matter and centrum semiovale(P=0.004-0.040).For Group B,the MTR values were slightly reduced,and the APTw values were slightly increased compared with the normal controls,but the differences were not statistically significant(P>0.05).Interpretation:For DD patients showing signs of delayed myelination on MRI,MTR and APTw imaging can help to diagnose myelination delay by quantifying semi-solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level,providing a new method for comprehensive evaluation of DD.For DD patients with normal myelination on MRI,the clinical values of MTR and APTw imaging remain to be explored.展开更多
Per-and polyfluoroalkyl substances(PFAS),colloquially known as“forever chemicals,”have emerged as a significant environmental and public health concern due to their extraordinary chemical stability and bioaccumulati...Per-and polyfluoroalkyl substances(PFAS),colloquially known as“forever chemicals,”have emerged as a significant environmental and public health concern due to their extraordinary chemical stability and bioaccumulative nature.1 PFAS exposure is linked to a range of adverse health outcomes,including developmental delays in children,elevated cholesterol levels,immune system impairments,and various cancers.展开更多
To editor:The EBF3(early B cytokine 3)gene encodes early and highly conserved B cytokine transcription factors that play crucial roles in B lymphocyte differentiation,skeletal phylogeny,and the genesis and differentia...To editor:The EBF3(early B cytokine 3)gene encodes early and highly conserved B cytokine transcription factors that play crucial roles in B lymphocyte differentiation,skeletal phylogeny,and the genesis and differentiation of neurons.These transcription factors are highly expressed in the developing nervous system.Heterozygous mutations or deletions of the EBF3 gene can lead to autosomal dominant HADDS(Hypotonia,Ataxia,and Delayed Development Syndrome),characterized by intellectual disability,neurodevelopmental disorders(NDDs),and facial malformations.1 Written informed consent has been obtained for the publication.展开更多
Background The PACS gene family has been demonstrated to be related to intracellular vesicular trafficking.The phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy,intellectual disabili...Background The PACS gene family has been demonstrated to be related to intracellular vesicular trafficking.The phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy,intellectual disability/developmental delay,and malformations,such as facial abnormalities.Methods We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation sequencing.Detailed information obtained from these patients was analyzed along with that obtained from previously reported patients.Results With the inclusion of the newly diagnosed cases in this study,103 cases with PACS gene family-related neurological diseases were reported,of which 43 were PACS2-related cases and the remaining were PACSI-related cases.Most patients had seizures,which have been reported to be effectively controlled by several types of anti-seizure medications(ASMs).The most efficacious and frequently prescribed ASMs included sodium valproate(43.3%,13/30),oxcarbazepine/carbamazepine(26.7%,8/30),and levetiracetam(20%,6/30).Almost all patients had intellectual disability/developmental delay.The most common pathogenic missense variants were PACSI p.Arg203Trp and PACS2 p.Glu209Lys.In addition,we report a patient carrying a likely pathogenic copy number variation(CNV)(de novo heterozygous deletion of chr14:105821380-106107443,286 kilobase,destroyed part of the furin-binding region domain and the protein structure after it)with more severe and refractory late-onset epilepsy.Conclusions The clinical phenotypes of the different PACS heterozygous missense variants were similar.The pathogenic variant sites of PACSI and PACS2 were quite limited but located in different regions.A CNV destroying part of the PACS2 gene might also be pathogenic.These findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family.展开更多
文摘BACKGROUND Visual impairment during early childhood can hinder motor,language,and social development,yet data on its developmental impact across common pediatric ocular diseases remain limited.AIM To investigate the developmental impact of low vision and blindness on children under six with common ocular diseases.METHODS This retrospective study reviewed records of new patients under six with visual impairment at Siriraj Hospital’s low vision rehabilitation center(January 2017-October 2022).We collected ocular,systemic,and developmental data;recorded visual acuity in the better-seeing eye after refractive correction;and assessed developmental domains with the DenverⅡ.Univariable and multi-variable logistic regression identified factors associated with developmental delay.RESULTS A total of 161 pediatric patients(mean age 24.9±18.9 months)were enrolled and evaluated based on their ability to fix on and follow an object or light source.Some were further assessed using the Allen picture chart and all had visual acuity worse than 1.07±0.58 LogMAR,and 83.2%were identified as having global developmental delay(GDD).The three most common ocular causes were cortical visual impairment(CVI),optic neuropathy/atrophy,and optic nerve hypoplasia.Extremely poor visual acuity(inability to fixate and follow)was significantly associated with GDD[adjusted odds ratio(AOR)41.0]and delays in all developmental domains:Gross motor(AOR 10.0),fine motor(AOR 12.8),language(AOR 5.3),and personal-social skills(AOR 13.4)(P≤0.002).Multiple disabilities,most often visual impairment with cerebral palsy,were also significantly associated with gross motor delays(AOR 7.7)and fine motor delays(AOR 4.0)(P<0.05).CVI was also related to delays in language and personal-social skills(AOR 9.1 each)(P<0.05).CONCLUSION This study underscores the developmental issues in children with visual impairment,especially those with poorer acuity,CVI,and multiple disabilities.Significant delays were observed in all domains,including GDD.A timely referral to specialists is strongly recommended.
文摘BACKGROUND Unintended pregnancy occurs when an individual or couple conceives without planning or desire,which can potentially affect a child’s physical,mental,and social well-being.This can then lead to long-term socioeconomic challenges for families and communities.Although its impact on child growth and development is a pressing concern,research remains limited particularly in multicenter settings.AIM To examine the long-term consequences of unintended pregnancy on the critical years of early childhood growth and development.METHODS This analytical observational study employed a case-control design and was conducted in research centers across Indonesia,encompassing those located in Central Java,Lampung,Bali,and West Nusa Tenggara.A total of 700 children aged≤5 years with histories of intended or unintended pregnancies participated.Data collection involved structured interviews and direct anthropometric and developmental assessments.Data analyses were conducted using multivariate statistics and partial least squares structural equation modeling.RESULTS Unintended pregnancy was found to have a statistically significant effect on both child growth(t=8.178;P<0.001)and child development(t=25.688;P<0.001).Key growth problems identified included underweight,undernutrition,abnormal head circumference,and stunting.Developmental challenges prominently associated with unintended pregnancy included behavioral and emotional disorders,autism spectrum disorder,attentiondeficit/hyperactivity disorder,social and motor skill deficits,as well as visual and hearing impairments.CONCLUSION Unintended pregnancy significantly affects child growth and development,underscoring the need for early intervention,quality prenatal care,and strengthened family planning policies.
基金Supported by National Administration of Traditional Chinese Medicine,No.2019XZZX-EK002.
文摘BACKGROUND Xia–Gibbs syndrome(XGS,OMIM:615829),caused by mutations within the ATHook DNA-binding motif-containing protein 1(AHDC1)gene(OMIM:615790),located on the short arm of chromosome 1 within the cytogenetic band 1p36.11,contains five noncoding 5 exons,a single 4.9-kb coding exon,and a noncoding 3 exon.CASE SUMMARY In this case report,we diagnosed and treated a 6-mo-old girl with XGS.The primary clinical symptoms included global developmental delay,hypotonia,and mild dysmorphic features.Using high-throughput whole-exosome sequencing to sequence the patient and her parents,and the results showed a novel frameshift mutation of c.1155dupG(p.Arg386Alafs*3)in the AHDC1 gene.The paternal gene was wild type.CONCLUSION This report extends the mutation spectrum of the AHDC1 gene to provide the diagnostic basis for genetic counseling in families with XGS.
文摘<strong>Background:</strong> Childhood cataract causing visual impairment can compound developmental delay (DD) if left untreated. Current literature in children with DD is limited;thus, we evaluated cataract etiology, challenges, and treatment compliance in this group. <strong>Purpose:</strong> To report the presentation and challenges associated with cataract management in children with developmental delay (DD) at a tertiary care pediatric hospital. <strong>Methods:</strong> Retrospective review of 100 patients (173 eyes) presenting with cataracts and DD from February 2014 to December 2017. <strong>Results:</strong> 100 patients (173 eyes) were included. 27 patients had unilateral cataracts and 73 bilateral. The average age was 120.55 months (SD 63.77, range 5.87 - 243.16);the average follow-up period was 57.7 months (SD 139.14, range 1.03 - 1412.30). 61% of patients (55% eyes) underwent medical management for cataracts due to: cataract was not visually significant (66% eyes), parent deferred surgery (11% eyes), self-abusive behavior (14% eyes), and medical conditions that limited visual recovery (9% eyes). 32% of patients were unable to perform objective visual acuity by age 5. Patients with self-abusive behavior were more likely to present with or develop retinal detachment (RD) (35%) compared to those without self-abusive behavior (6%) (p = 0.0028). A statistically significant difference in the difficulty of examination (p < 0.0001) and poor compliance of glasses wear (p < 0.0001) was found in nonverbal patients. Surgical complications occurred in 39% of eyes. Those with intraocular lens placement after cataract extraction were more likely to develop visual axis opacification (27% eyes) than those who remained aphakic (9% eyes) (p = 0.0313). <strong>Conclusion:</strong> Cataract extraction in pediatric patients with DD can be associated with success, however, providers should prepare for limitations in managing these patients.
文摘The objective of this original pilot study was to determine if the Drums Alive<span style="white-space:nowrap;"><sup>®</sup></span> Kids Beats intervention could provide statistically significant improvements to physical and motor skill performance on participants with Developmental Delays (DD) using the Dusseldorf Motor-Proficiency-Test for children (MOT 4-6) model. The researchers selected the research-based Drums Alive Kids Beat intervention because of its multidisciplinary methodology that in previous studies demonstrated positive effects on physiological, psychological, neurological, educational, rhythmical, and socio-emotional literacy. Facilitators used standardized Drums Alive approved lesson plans and equipment to conduct the intervention through a battery of music, movement and drumming-centered exercises and activities. The 30 participants were German students between 4.9 and 10.2 years of age, without any inclusion or exclusion characteristics, who were divided into three groups consisting of two intervention groups: IG Kindergarten (IG Kinder), IG Elementary<span style="font-family:;" "=""><span style="font-family:Verdana;"> (IG Elem) with varied physical, social, and emotional DD that affected gross and fine motor skills, movement, coordination, and behavioral control;and, a Control Group (CG) that had normal physical and motor skill development (</span><b><span style="font-family:Verdana;">Table 1</span></b><span style="font-family:Verdana;">). The results of the study suggested that the Drums Alive Kids Beats intervention provided statistically significant improvements in physical and motor skill performance in children with DD, namely, 24% improvement (IG Kinder), 14% (IG Elem) vice a minor 4% improvement (CG). Of note, during this study to measure physical capability pre- and post-intervention, the facilitators noticed significant improvements in behavior in both IG groups;therefore, they chose to conduct a collateral study to measure six behavioral domains which will be documented in a future publication to demonstrate the exclusive relationship between the Drums Alive Kids Beats intervention and improvement in behavior.</span></span>
文摘Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation. WTK1 cells contain a p53 mutation, whereas the TK6 cell line has the native p53 tumor-suppressor gene. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. Using probes that target specific regions on chromosomes associated with a distinct subset of microdeletions and microduplications either established or thought to be responsible for intellectual disability or developmental delay, we have demonstrated that WTK1 and TK6 are not impacted in the same way by irradiation. Instead, each cell line presents its own unique MLPA profile. The most notable differences are the appearance of nine unique probe signals only seen in WTK1 cells. These results are important in the study of how different cell lines can be affected in significantly different ways depending on the presence or absence of wild type p53.
基金Supported by the Russian Science Foundation Grant,No.24-45-00067.
文摘BACKGROUND Autism spectrum disorders(ASD)represent a substantial social problem affecting at least 1 in 100 children worldwide.These conditions are very often accompanied by intellectual disability(ID)and speech delay;thus,they can be considered within a clinical continuum of neurodevelopmental disorders.Given the high heterogeneity of ASD,the subjective nature of diagnostic criteria,and the presence of phenocopies,identifying genetic determinants of these disorders remains a challenge.AIM To investigate the spectrum and frequency of rare genetic variants in genes with proven association with ASD in Russian children.METHODS 110 patients from 106 families were recruited into the study mean age at diagnosis 6 years;boy-to-girl ratio 3:1.Most of the patients(84%)demonstrated a combination of ASD with developmental delay(DD)or ID.Patients with syndromic features were subjected to the chromosomal microarray analysis.The remained children underwent clinical exome sequencing aimed at identifying presumably monogenic causes of ASD.The study focused on rare(minor allele frequency≤0.001)variants affecting high-confidence ASD-associated genes.RESULTS Pathogenic copy number variations were detected in three(7%)of the patients examined.Clinical exome sequencing revealed pathogenic/likely pathogenic variants in 12 of 105 cases(11%),indicating the presence of monogenic syndromes with established clinical significance(Pitt-Hopkins syndrome,ZTTK syndrome,syndromic X-linked ID of Billuart type,Snijders-Blok-Campeau,Helsmoortel-van der Aa,Coffin-Siris,Clark-Baraitser,Keefstra syndromes,etc.).In addition,27 patients(26%)had 37 rare variants of unknown clinical significance in DSCAM,SHANK2,AUTS2,ADNP,ANKRD11,APBA2,ARID1B,ASTN2,ATRX,SCN1A,CHD2,DEAF1,EHMT1,GRIN2B,NBEA,NR4A2,TRIO,TRIP12,POGZ,EP300,FOXP1,PCDH19,GRIN2A,NCKAP1,and CHD8 genes.No specific variant was detected more than once in unrelated patients.Among the genes with rare variants found in 2 or more patients were TRIP12(n=4),AUTS2(n=3),ARID1B(n=3),PCDH19(n=3),EP300(n=3),TRIO(n=2),ASTN2(n=2),EHMT1(n=2),and CHD2(n=2).Of note,5 male ASD/DD patients from 3 unrelated families had PCDH19 missense variants,confirming that at least some hemizygous males with non-mosaic PCDH19 variants may present with neurobehavioral abnormalities.These variants did not cause epilepsy restricted to females in patients’mothers or sisters.CONCLUSION These data confirm a tremendous diversity of genetic causes of ASD.Clinical exome sequencing may serve as a reasonable alternative to whole-exome sequencing.
文摘The article published in World Journalof Pediatrics entitled as"Introducing PRIDE:Development and Validation of a Developmental Delay Screening Tool in a Community Population"by Wu et al.[1]presents an innovative use of item response theory to develop and validate the Parent-Reported Indicator of Developmental Evaluation for Chinese Children(PRIDE)tool.
基金supported by the Natural Science Foundation of Zhejiang Province(LQ23H090002)the National Natural Science Foundation of China(82201607).
文摘Cortical malformations,including focal cortical dysplasia type II(FCDII),are a common cause of drug-resistant epilepsy and developmental delay.Consideration of surgery has become the standard of care for those patients.However,10%-50% of patients with FCD experience post-surgical relapses[1],and many do not even qualify as surgical candidates.Effective treatments for FCD-associated epilepsy are lacking.
基金supported by the Shanghai Municipal Commission of Science and Technology Research Project(China)(No.19JC1411001)the National Key Research and Development Program from the Ministry of Science and Technology of the People’s Republic of China(No.2021YFC2700800)+4 种基金the National Natural Science Foundation of China(No.31972880,32170615,31611130035,31371274)the National Key Research and Development Plan for Stem Cell and Transformation Research(China)(No.2017YFA0104202)the Collaborative Innovation Center Project Construction for Shanghai Women and Children’s Health,the Open Research Fund of National Health Commission Key Laboratory of Birth Defects Prevention&Henan Key Laboratory of Population Defects Prevention(China)(No.ZD202309)The Medical Science and Technology Research Program Project of Henan Province,China(No.LHGJ20230368)the Postdoctoral Research Fund of the Third Affiliated Hospital of Zhengzhou University(No.BSH20230101).
文摘Global developmental delay/intellectual disability(GDD/ID)with a prevalence of 1%e3%represents one of the biggest medical and social challenges in our society.^(1)Genetic factors are the main causes of GDD/ID and early diagnosis is crucial to improving the prognosis of GDD/ID children.^(2)Chromosomal microarray analysis,as a first-tier clinical test,^(3)remains limited because of the insufficient to detect small variations while whole exome sequencing(WES)can detect both single-nucleotide variants(SNVs)and copy-number variants(CNVs),effectively improving the diagnostic yield of GDD/ID.
基金Supported by the National Natural Science Foundation of China,No.82205190the Foundation for Distinguished Young Talents in Higher Education of Henan,No.[2018]16
文摘BACKGROUND Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities(NECRC)is a rare,autosomal,dominant neurological disorder caused by mutations in the ZMYM2 gene.To date,the clinical and functional characteristics of the novel ZMYM2 mutation c.2090_2091del have not yet been reported.CASE SUMMARY The patient was an 18.5-mo-old Chinese boy with motor and language delay,microcephaly,facial dysmorphism,moderate malnutrition,single palmar crease on the left hand,synpolydactyly of the right foot,hypotonia and feeding problems.The boy who was diagnosed with NECRC was enrolled in the First Affiliated Hospital,Henan University of Chinese Medicine,and his clinical data were collected.From the whole-exon sequencing(WES)data,the pathogenic SNVs/InDels were identified,and the molecular findings were characterized.WES revealed that the heterozygous variant in the ZMYM2 gene was c.2090_20-91del,p.Ser697TrpfsTer3,a frameshift mutation,which is a NECRC-related gene mutation.CONCLUSION We performed a systematic literature review to identify and characterize NECRC.Substantial evidence from the literature indicated that patients with ZMYM2 gene mutation showed different degrees of intellectual disability,motor and language retardation,facial dysmorphism,and a few had congenital heart defects,kidney and urinary tract abnormalities.Early diagnosis and prompt management with comprehensive rehabilitation training are beneficial,but may not improve long-term outcomes.
文摘Objective: to explore the characteristics and clinical significance of cranial MRI in children with mental retardation/comprehensive developmental retardation (ID/GDD) caused by genetic factors. Methods: a retrospective study was conducted to analyze the cranial MRI of 51 children eligible for inclusion. Results: 8 cases (15.69%) had extra-cerebral space widening, 16 cases (31.37%) had abnormal ventricular system, 13 cases (25.49%) had abnormal white matter myelination, 6 cases (11.76%) had abnormal cerebral cortex development, 15 cases (29.41%) had abnormal corpus callosum development, 7 cases (13.73%) had abnormal cerebellum development, 10 cases (19.61%) had other or special abnormalities, 12 cases (23.53%) had no abnormality, 24 cases (47.06%) had multiple abnormalities. Conclusion: cranial MRI is of great significance in the etiological diagnosis of ID/GDD and can assist in the selection of genetic testing methods.
文摘Importance:Understanding the significance of motor skills in promoting physical fitness(PF)can offer valuable insights for devising comprehensive intervention and clinical rehabilitation programs for children with global developmental delay(GDD).However,it remains unclear whether fundamental motor skills(FMS)can improve the PF of children with GDD.Objective:To investigate the correlation between FMS and PF in children with GDD.Methods:A total of 180 children with GDD and 180 typically developing(TD)children aged 3-5 years were selected.All participants completed the Gesell Developmental Schedule,FMS,and PF tests at Beijing Children’s Hospital between September 2022 and August 2023.Partial correlation and regression analyses were performed to examine the relationship between FMS and PF.Results:Children with GDD had significantly lower FMS and PF scores compared to TD children(P<0.05).No significant differences were found between males and females with GDD in FMS and PF score(P>0.05).A more severe developmental delay was associated with lower FMS and PF scores.The correlation coefficients between individual FMS items and individual PF items,as well as the total PF score,ranged from 0.20 to 0.56.Regression analysis indicated that manual dexterity(β=0.241,P=0.029)and body balance(β=0.399,P=0.001)significantly predicted the total PF score.Interpretation:In children with GDD,both FMS and PF are underdeveloped.Focusing on motor skills development is vital for promoting their PF.
文摘45X/46XY mosaicism is a rare chromosome disease. The apparent prevalence of males and females with 45X/46XY is 5.6 and 2.1 per 100,000 liveborn males and females. We present a boy who had a developmental delay with hypospadias. He was referred to pediatric genetics and was diagnosed with 45X/46XY mosaicism by peripheral blood chromosome examination. During serial rehabilitation programs, his speech delay was caught up. But his poor attention and hyperactivity are obvious progressively. We should pay attention to these patients, not only physical conditions but also psychological problems.
基金the Chinese National Natural Science Foundation(No.8 1000346,Y.G.Y.)foundation grant from the Center for Clinical Nutrition Study(SCMC-YP-HOPE-KY-0905 for Y.G.Y)+5 种基金Health Science grant from the social development branch of Pudong New District(PW2009D-9 for Y.G.Y)the Simons Foundation(J.F.G.)Autism Speaks(J.F.G.)Developmental Genome Anatomy Project(P01 GM061354)Chinese National"973"Project on Population and Health(No.2010CB529601,B.-L.W.)Science and Technology Council of Shanghai(No.09JC1402400(B.-L.W.)
文摘Recurrent genomic imbalances at 16p 11.2 are genetic risk factors of variable penetrance for developmental delay and autism.Recently, 16pl 1.2（chr16：29.5 Mb-30.1 Mb） deletion has also been detected in individuals with early-onset severe obesity.The penetrance of 16p11.2 deletion as a genetic risk factor for obesity is unknown.We evaluated the growth and body mass characteristics of 28 individuals with 16p11.2 （chr16：29.5 Mb-30.1 Mb） deletion originally ascertained for their developmental disorders by reviewing their medical records.We found that nine individuals could be classified as obese and six as overweight.These individuals generally had early feeding and growth difficulties,and started to gain excessive weight around 5-6 years of age.Thirteen out of the 18 deletion carriers aged 5 years and older（72%） were overweight or obese,whereas only two of 10 deletion carriers（20%） younger than five were overweight or obese.Males exhibited more severe obesity than females.Thus,the obesity phenotype of 16p11.2 deletion carriers is of juvenile onset,exhibited an age- and gender-dependent penetrance. 16p11.2 deletion appears to predispose individuals to juvenile onset obesity and in this case are similar to the well-described Prader-Willi syndrome（PWS）.Early detection of this deletion will provide opportunity to prevent obesity.
文摘BACKGROUND Special AT-rich sequence binding protein 2(SATB2)-associated syndrome(SAS;OMIM 612313)is an autosomal dominant disorder.Alterations in the SATB2 gene have been identified as causative.CASE SUMMARY We report a case of a 13-year-old Chinese boy with lifelong global developmental delay,speech and language delay,and intellectual disabilities.He had short stature and irregular dentition,but no other abnormal clinical findings.A de novo heterozygous nonsense point mutation was detected by genetic analysis in exon 6 of SATB2,c.687C>A(p.Y229X)(NCBI reference sequence:NM_001172509.2),and neither of his parents had the mutation.This mutation is the first reported and was evaluated as pathogenic according to the guidelines from the American College of Medical Genetics and Genomics.SAS was diagnosed,and special education performed.Our report of a SAS case in China caused by a SATB2 mutation expanded the genotype options for the disease.The heterogeneous manifestations can be induced by complicated pathogenic involvements and functions of SATB2 from reviewed literatures:(1)SATB2 haploinsufficiency;(2)the interference of truncated SATB2 protein to wild-type SATB2;and(3)different numerous genes regulated by SATB2 in brain and skeletal development in different developmental stages.CONCLUSION Global developmental delays are usually the initial presentations,and the diagnosis was challenging before other presentations occurred.Regular follow-up and genetic analysis can help to diagnose SAS early.Verification for genes affected by SATB2 mutations for heterogeneous manifestations may help to clarify the possible pathogenesis of SAS in the future.
文摘Importance:The process of brain development in children with developmental delay is not well known.Amide proton transfer-weighted(APTw)imaging is a novel molecular magnetic resonance imaging(MRI)technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process,and may be useful for providing insights into brain development.Objective:To assess the contribution of amide proton transfer-weighted(APTw)imaging and magnetization transfer(MT)imaging to the evaluation of children with developmental delay(DD).Methods:Fifty-one patients with DD were recruited to this study.The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging(MRI).Thirty patients(10 girls,20 boys;age range:1-8 months;median age:4 months)in group A showed delayed myelination on MRI,while 21 patients(3 girls,18 boys;age range:12-36months;median age:25months)in group B showed normal myelination on MRI.Fifty-one age-and sex-matched children with normal developmental quotient(DQ)and normal MRI appearance were recruited as normal controls.Three-slice APTw/MT axial imaging was performed at the level of the centrum semiovale,the basal ganglia and the pons.Quantitative data of the MT ratio(MTR)and APTw were analyzed for multiple brain regions.Independent-samplet-tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls.Analysis of Covariance was conducted to correct the statistical results.The level of statistical significance was set toP<0.05.Results:For group A,the MTR values were lower in all regions(P=0.004-0.033)compared with the normal controls,while the APTw values were higher in the pons,middle cerebellar peduncle,corpus callosum,frontal white matter,occipital white matter and centrum semiovale(P=0.004-0.040).For Group B,the MTR values were slightly reduced,and the APTw values were slightly increased compared with the normal controls,but the differences were not statistically significant(P>0.05).Interpretation:For DD patients showing signs of delayed myelination on MRI,MTR and APTw imaging can help to diagnose myelination delay by quantifying semi-solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level,providing a new method for comprehensive evaluation of DD.For DD patients with normal myelination on MRI,the clinical values of MTR and APTw imaging remain to be explored.
基金support from an Australian Research Council Industry Fellowship Grant(IE230100593)the National Natural Science Foundation of China(42177386)the National Key Research and Development Program of China(no.2020YFC1808201).
文摘Per-and polyfluoroalkyl substances(PFAS),colloquially known as“forever chemicals,”have emerged as a significant environmental and public health concern due to their extraordinary chemical stability and bioaccumulative nature.1 PFAS exposure is linked to a range of adverse health outcomes,including developmental delays in children,elevated cholesterol levels,immune system impairments,and various cancers.
基金supported by the Medical Research Project of the Chengdu Health Commission(202321).
文摘To editor:The EBF3(early B cytokine 3)gene encodes early and highly conserved B cytokine transcription factors that play crucial roles in B lymphocyte differentiation,skeletal phylogeny,and the genesis and differentiation of neurons.These transcription factors are highly expressed in the developing nervous system.Heterozygous mutations or deletions of the EBF3 gene can lead to autosomal dominant HADDS(Hypotonia,Ataxia,and Delayed Development Syndrome),characterized by intellectual disability,neurodevelopmental disorders(NDDs),and facial malformations.1 Written informed consent has been obtained for the publication.
基金supported by the National Key Research and Development Program of China(No.2020YFA0804000)the National Natural Science Foundation of China(Nos.81971211,12026606,and 81601131)+5 种基金Key Project of Clinical Medicine Research of National Clinical Research Center for Child Health and Disorders,Children's Hospital of Chongqing Medical University(No.NCRCCHD-2021-KP-02)Beijing Natural Science Foundation(No.7212109)the Beijing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases(No.BZ0317)the Capital Health Research and Development of Special Fund(No.2020-1-4071)National High Level Hospital Clinical Research Funding(Scientific Research Seed Fund of Peking University First Hospital)(No.2022SF29)the Fundamental Research Funds for the Central Universities(Nos.BMU2017JI002,BMU2018XY006,and PKU2017LCX06)。
文摘Background The PACS gene family has been demonstrated to be related to intracellular vesicular trafficking.The phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy,intellectual disability/developmental delay,and malformations,such as facial abnormalities.Methods We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation sequencing.Detailed information obtained from these patients was analyzed along with that obtained from previously reported patients.Results With the inclusion of the newly diagnosed cases in this study,103 cases with PACS gene family-related neurological diseases were reported,of which 43 were PACS2-related cases and the remaining were PACSI-related cases.Most patients had seizures,which have been reported to be effectively controlled by several types of anti-seizure medications(ASMs).The most efficacious and frequently prescribed ASMs included sodium valproate(43.3%,13/30),oxcarbazepine/carbamazepine(26.7%,8/30),and levetiracetam(20%,6/30).Almost all patients had intellectual disability/developmental delay.The most common pathogenic missense variants were PACSI p.Arg203Trp and PACS2 p.Glu209Lys.In addition,we report a patient carrying a likely pathogenic copy number variation(CNV)(de novo heterozygous deletion of chr14:105821380-106107443,286 kilobase,destroyed part of the furin-binding region domain and the protein structure after it)with more severe and refractory late-onset epilepsy.Conclusions The clinical phenotypes of the different PACS heterozygous missense variants were similar.The pathogenic variant sites of PACSI and PACS2 were quite limited but located in different regions.A CNV destroying part of the PACS2 gene might also be pathogenic.These findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family.
