Global developmental delay (GDD)/intellectual disability (ID) is common in children and its etiology is unknown in many cases. Chromosomal abnormalities are predominant genetic causes of GDD/ID. The aim of this study is to determine the genetic risk factors that may be involved in the etiology of GDD/ID. In this study, 810 children with moderate to severe, clinically unexplained GDD/ID for whom cytogenetic analysis were performed were retrospectively rescreened. The results showed that GDD/ID affected more females than males (2 girls:1 boy). A total of 54 children (6.7%) with GDD showed chromosomal aberrations (CAs): 59.3% of these CAs were structural aberrations, and the rest were numerical aberrations (40.7%). Specifically, inversions, deletions, and reciprocal and robertsonian translocations, which were detected in 1, 0.7, 0.8, and 0.4% of the children, respectively, constituted important categories of structural CAs. Among numerical CAs, classic Turner and mosaics were detected in 1.2% of all children. Trisomy 21 and mosaic trisomy 21 were detected in 1% of the children. Marker chromosomes and 47,XXY karyotypes were found in two children each. Our results suggest that female sex is more affected by CAs among GDD/ID cases, and cytogenetic analysis is useful in the etiological diagnosis of GDD/ID.

BACKGROUND: NARS2 as a member of aminoacyl-tRNA synthetases was necessary to covalently join a specific tRNA to its cognate amino acid. Biallelic variants in NARS2 were reported with disorders such as Leigh syndrome, deafness, epilepsy, and severe myopathy.
METHODS: Detailed clinical phenotypes were collected and the NARS2 variants were discovered by whole exome sequencing and verified by Sanger sequencing. Additionally, 3D protein structure visualization was performed by UCSF Chimera. The proband in our study had early-onset status epilepticus with abnormal EEG and MRI results. She also performed global developmental delay (GDD) and myocardial dysfunction. Next-generation sequencing (NGS) and Sanger sequencing revealed compound heterozygous missense variants [NM_024678.6:exon14: c.1352G > A(p.Arg451His); c.707T > C(p.Phe236Ser)] of the NARS2 gene. The proband develops refractory epilepsy with GDD and hyperlactatemia. Unfortunately, she finally died for status seizures two months later.
CONCLUSIONS: We discovered two novel missense variants of NARS2 in a patient with early-onset status epilepticus and myocardial dysfunction. The NGS enables the patient to be clearly diagnosed as combined oxidative phosphorylation deficiency 24 (COXPD24, OMIM:616,239), and our findings expands the spectrum of gene variants in COXPD24.

Background Global developmental delay (GDD) is common and has a significant impact on affected children, families, and society. Understanding its etiology is crucial for management and prevention strategies. However, data on the etiological profile of GDD in developing countries are limited. This study aimed to identify the etiological profile of GDD at a tertiary care hospital in India. Methodology This observational study included children aged three months to five years with a developmental quotient below 70%. Data on demographics, clinical features, relevant investigations, and diagnoses were collected. Etiologies were categorized into prenatal, perinatal, postnatal, and unknown causes. Informed consent was obtained from the parents. Results A total of 52 children, with a median age of 15.5 months, were included in the study, with 69.2% being males. Prenatal causes accounted for half of the cases, with genetic abnormalities (32.7%) and chromosomal abnormalities (7.7%) being prominent. Perinatal causes were the next most common (34.6%), including hypoxic-ischemic encephalopathy (26.7%). Postnatal causes were rare (3.8%). The overall etiological yield was 88.4%, with some cases remaining unidentified. Conclusions Prenatal causes, including genetic and chromosomal abnormalities, are common in GDD. The utilization of genetic testing enhances etiological yield. Hypoxic-ischemic encephalopathy remains a significant factor and highlights the importance of perinatal care in preventing developmental delays. Large multicentric studies are needed for a comprehensive database of etiological profiles.

The purpose of this study was to identify developmental profiles associated with autism spectrum disorder (ASD) and global developmental delay (DD) in pre-school aged Italian children. Developmental profiles were evaluated by means of a standardized tool widely used for the assessment of psychomotor development in early childhood, the Griffiths III scales, recently adapted and standardized for the Italian population. Specifically, we compared the Griffiths III profiles of children with ASD and DD (ASD + DD) with those of children with DD alone. Moreover, we inspected the psychometric function of single items by comparing children with ASD + DD and children with DD with typically developing (TD) children from the Griffiths III normative sample. In this way, we aimed to isolate the effects of each diagnostic class on psychomotor abilities and on the psychometric function of single items. The ASD + DD and DD groups were found to share the presence of lower age equivalent scores relative to their chronological age in all the developmental domains considered: Foundations of Learning, Language and Communication, Eye and Hand Coordination, Personal-Social-Emotional and Gross Motor Skills. However, the DD group displayed a homogeneous profile with similar levels of delay in all developmental domains, while children with ASD + DD exhibited relative weaknesses in the Language and Communication and Personal-Social-Emotional scales. The analysis of the psychometric function drawn for each item has confirmed different profiles in social-communicative and non-verbal items between the two diagnostic groups and in relation to TD normative sample. The Griffiths III is a valid psychometric tool for identifying atypical developmental profiles and its use may be recommended during the diagnostic process of ASD and DD, to detect specific strengths and weaknesses and guide person-centered treatment.

UNASSIGNED: The co-presentation of severe obesity (SO) and global developmental delay (GDD) in Canadian preschool children has not been examined. However, SO and GDD may require syndromic diagnoses and unique management considerations.
UNASSIGNED: To determine (1) minimum incidence; (2) age of onset and risk factors; and (3) health care utilization for co-presenting SO and GDD.
UNASSIGNED: Through the Canadian Paediatric Surveillance Program (CPSP), a monthly form was distributed to participants from February 2018 to January 2020 asking for reports of new cases of SO and GDD among children ≤5 years of age. We performed descriptive statistics for quantitative questions and qualitative content analysis for open-ended questions.
UNASSIGNED: Forty-seven cases (64% male; 51% white; mean age: 3.5 ± 1.2 years) were included. Age of first weight concern was 2.5 ± 1.3 years and age of GDD diagnosis was 2.7 ± 1.4 years. Minimum incidence of SO and GDD was 3.3 cases per 100,000 for ≤5 years of age per year. Identified problems included school and/or behavioural problems (n = 17; 36%), snoring (n = 14; 30%), and asthma/recurrent wheeze (n = 10; 21%). Mothers of 32% of cases (n = 15) had obesity and 21% of cases (n = 10) received neonatal intensive care. Microarray was ordered for 57% (n = 27) of children. A variety of clinicians and services were accessed. As reported by CPSP participants, challenges faced by families and health service access were barriers to care.
UNASSIGNED: Children with SO and GDD have multiple comorbidities, and require early identification and referral to appropriate services. These cases may also benefit from additional testing to rule out known genetic obesity syndromes.

UNASSIGNED: Early identification and intervention for children with global developmental delay (GDD) can significantly improve their prognosis and reduce the possibility of developing intellectual disability in the future. This study aimed to explore the clinical effectiveness of a parent-implemented early intervention program (PIEIP) for GDD, providing a research basis for the extended application of this intervention strategy in the future.
UNASSIGNED: During the period between September 2019 and August 2020, children aged 3 to 6 months diagnosed with GDD were selected from each research center as the experimental group and the control group. For the experimental group, the PIEIP intervention was conducted for the parent-child pair. Mid-term and end-stage assessments were performed, respectively, at 12 and 24 months of age, and parenting stress surveys were completed.
UNASSIGNED: The average age of the enrolled children was 4.56 ± 1.08 months for the experimental group (n = 153) and 4.50 ± 1.04 months for the control group (n = 153). The comparative analysis of the variation in the progress between the two groups by independent t-test showed that, after the experimental intervention, the developmental quotient (DQ) of locomotor, personal-social, and language, as well as the general quotient (GQ) of the Griffiths Mental Development Scale-Chinese (GDS-C), the children in the experimental group demonstrated higher progress than those in the control group (P < 0.05). Furthermore, there was a significant decrease in the mean standard score of dysfunctional interaction, difficult children and the total level of parental stress in the term test for the experimental groups (P < 0.001 for all).
UNASSIGNED: PIEIP intervention can significantly improve the developmental outcome and prognosis of children with GDD, especially in the areas of locomotor, personal-social, and language.

UNASSIGNED: To use structural magnetic resonance imaging (3D-MRI) to evaluate the abnormal development of the cerebral cortex in infants with global developmental delay (GDD).
UNASSIGNED: The GDD group includes 67 infants aged between 112 and 699 days with global developmental delay and who underwent T1-weighted MRI scans in Shanxi Children\'s Hospital from December 2019 to March 2022. The healthy control (HC) group includes 135 normal developing infants aged between 88 and 725 days in Shanxi Children\'s Hospital from September 2020 to August 2021. Whole-brain T1-weighted MRI scans were carried out with a 3.0-T magnetic resonance scanner, which was later processed using InfantSurfer to perform MR image processing and cortical surface reconstruction. Two morphological features of the cortical surface of the 68 brain regions were computed, i.e., the cortical thickness (CT) and cortical surface area (SA), and compared between the GDD and HC groups.
UNASSIGNED: With regard to the CT, the HC group showed a rapid decrease at first and then a slow increase after birth, and the CT of the GDD group decreased slowly and then became relatively stable. The GDD group showed bilaterally higher hemispherical average CT than those in the HC group. In detail, for the left hemisphere, except in the entorhinal and temporal poles in which the average CT values of the two brain regions were lower than those of the HC group, the CT of the 26 brain regions in the GDD group was higher than those of the HC group (p < 0.05). For the right hemisphere, the CT of the entorhinal in the GDD group was lower than that in the HC group. Otherwise, the CT of the remaining 28 brain regions was higher than those in the HC group (p < 0.05). With regard to the SA, both groups showed a rapid increase after birth till 23 months and remained quite stable afterward. The GDD group shows lower SA bilaterally than that in the HC group. In detail, SA in the GDD group was lower in most cortical regions of both hemispheres than in the HC group (p < 0.05), except for the right temporal pole and entorhinal. When testing for brain asymmetry, we found that the HC group showed obvious asymmetry of CT and SA, while only a few cortical regions in the GDD group showed asymmetry.

Background Developmental delay refers to the insufficient acquisition of age-appropriate developmental milestones. According to World Health Organization, approximately 5% of all children under the age of 14 years display some developmental disability. Aim and objective Our objective was to investigate the prevalence of abnormal magnetic resonance imaging (MRI) brain findings in pediatric patients with non-syndromic developmental delay and to establish the utility of MRI for the same. Material and Method This cross-sectional study prospectively enrolled 60 pediatric patients (three months to 12 years) and data were analyzed using SPSS software. Result Abnormalities on MRI were seen in 80% of cases, with findings indicating perinatal hypoxic insult (36.67%) being the most common, followed by structural abnormalities of the brain (20%). There was no significant difference in the prevalence of abnormal findings when classified by gender or age, or between global developmental delay (GDD) alone and GDD with epilepsy. However, perinatal hypoxic insult was significantly associated with GDD with epilepsy rather than GDD alone (p < 0.01). Conclusion In this study, brain MRI provides a high yield of abnormal findings and helps calculate the relative prevalence of various common etiologies in non-syndromic developmental delay. This study supports several international guidelines that include MRI as the first-line investigation for non-syndromic developmental delay.

Genome sequencing (GS) has been used in the diagnosis of global developmental delay (GDD)/intellectual disability (ID). However, the performance of GS in patients with inconclusive results from chromosomal microarray analysis (CMA) and exome sequencing (ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test before enrollment. Reanalysis of their CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 21%. Seven cases could have been solved with reanalysis of ES data. Thirteen families were missed by previous CMA/ES due to improper methodology. Two remained unsolved after ES reanalysis due to complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this undiagnosed GDD/ID cohort, detecting a wide range of variant types of different sizes in a single workflow.

OBJECTIVE: To study the clinical effect of mouse nerve growth factor (mNGF) in the treatment of children with global developmental delay (GDD).
METHODS: A prospective clinical trial was conducted in 60 children with GDD who were treated in the First Affiliated Hospital of Anhui Medical University between July 2016 and July 2017. These children were randomly divided into two groups: conventional rehabilitation treatment and mNGF treatment group (n=30 each). The children in the conventional rehabilitation treatment group were given neurodevelopmental therapy, and those in the mNGF treatment group were given mNGF treatment in addition to the treatment in the control group. The evaluation results of the Gesell Developmental Scale were compared between the two groups before and after treatment.
RESULTS: Before treatment and after 1.5 months of treatment, there was no significant difference in the developmental quotient (DQ) of each functional area of the Gesell Developmental Scale between the mNGF treatment and conventional rehabilitation treatment groups (P>0.05). After 3 months of treatment, the mNGF treatment group had significantly higher DQs of gross motor, fine motor, and personal-social interaction than the conventional rehabilitation treatment group (P˂0.05). The incidence rate of transient injection site pain after injection of mNGF was 7% (2/30), and there was no epilepsy or other serious adverse reactions.
CONCLUSIONS: In children with GDD, routine rehabilitation training combined with mNGF therapy can significantly improve their cognitive, motor, and social abilities.
目的: 观察鼠神经生长因子（mouse nerve growth factor，mNGF）治疗儿童全面性发育迟缓的临床疗效。方法: 前瞻性选取安徽医科大学第一附属医院2016年7月至2017年7月收治的60例全面性发育迟缓患儿，随机分为常规康复组与mNGF组，每组各30例。常规康复组采用神经发育学疗法，mNGF组在此基础上，联合mNGF治疗。比较两组患儿在治疗前、治疗中和治疗结束后Gesell发育量表评分的差异。结果: mNGF组和常规康复组治疗前、治疗1.5个月的Gesell发育量表各能区发育商（developmental quotient，DQ）差异无统计学意义（均P>0.05）。治疗3个月后，mNGF组大运动、精细运动和应人能区的DQ高于常规康复组（均P<0.05）。mNGF组一过性注射部位疼痛的发生率为7%（2/30），未发现癫痫等其他严重不良反应。结论: 联合应用mNGF治疗可显著改善全面性发育迟缓患儿的认知、运动和社交能力。.