OBJECTIVE:To investigate the genetic etiology of two pediatric patients presenting with developmental delay and microcephaly. METHODS:Two patients diagnosed with developmental delay and microcephaly at the Children's Hospital of Nanjing Medical University in February 2023 and March 2024 were enrolled. Peripheral blood samples were collected from both children and their parents. Genomic DNA was extracted and subjected to whole exome sequencing (WES). Suspected variants were verified by Sanger sequencing. Pathogenicity of the identified variants was assessed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Structural visualization of the variant proteins was performed using PyMOL software. A literature review was conducted to summarize reports on PCDH12 gene variants associated with Diencephalic-mesencephalic junction dysplasia syndrome type 1 (DMJDS1). This study was approved by the Medical Ethics Committee of Children's Hospital of Nanjing Medical University (Ethics No.: 202402022-1). RESULTS:Patient 1 was a 5-year and 9-month-old female with congenital microcephaly, global developmental delay, distinctive facial features, intellectual disability, gait instability, and ataxia. Brain MRI indicated cerebral dysgenesis. WES revealed compound heterozygous PCDH12 variants: paternal c.522_525delGTCT (p.S175Pfs*22) and maternal c.244G>T (p.E82*). Both variants were classified as pathogenic according to ACMG guidelines. Patient 2 was a 7-day-old male. Prenatal ultrasound showed microcephaly, and fetal MRI revealed a thin corpus callosum. Postnatally, he exhibited primary microcephaly, global developmental delay, and brain MRI findings included widened lateral ventricles, thin corpus callosum, and abnormal morphology of the bilateral cerebral peduncles. WES identified compound heterozygous PCDH12 variants: maternal c.522_525delGTCT (p.S175Pfs*22) and paternal c.466delC (p.L156Wfs*42). The c.466delC variant was classified as pathogenic. Based on the clinical phenotypes and genetic findings, both patients were diagnosed with DMJDS1. PyMOL analysis indicated that all three PCDH12 variants result in protein truncation. A review of 12 published articles identified 44 reported DMJDS1 cases (including the 2 cases in this study) associated with 19 distinct PCDH12 variants, of which only one previous case involved compound heterozygosity; all others were homozygous. CONCLUSION:Compound heterozygous variants in the PCDH12 gene are likely the genetic cause of microcephaly and developmental delay in these two patients. The c.244G>T and c.466delC variants are novel, thereby expanding the mutational spectrum of the PCDH12 gene.

OBJECTIVE:To elucidate the clinical phenotype and molecular genetic characteristics of intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities (MRD50) due to variants of NAA15 gene. METHODS:A retrospective analysis was carried out on the clinical data of four MRT50 pedigrees (7 patients in total) diagnosed at the Children's Hospital of Nanjing Medical University between February 2022 and August 2024. Pathogenic variants carried by the patients were screened through whole exome sequencing and validated by Sanger sequencing in the respective pedigrees. Bioinformatics tools including MaxEntScan, dbscSNV, RDDC, and SpliceAI were employed to predicted the pathogenicity of splice-site variants. The functional impact of the c.692-5A>G splice-site variant was assessed by reverse transcription-PCR (RT-PCR) combined with agarose gel electrophoresis. PyMOL software was used to predict three-dimensional conformational changes of the variant proteins. Additionally, quantitative real-time PCR (qPCR) was applied to determine the mRNA expression of the NAA15 gene in the peripheral blood sample from the patients. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 202402022-1). RESULTS:The patients (3 males and 4 females), with a last follow-up age ranging from 5-year-and-1-month-old to 35 year old, exhibited varying degrees of intellectual disability, language delay, and learning difficulties. Among them, 3 cases were accompanied by motor developmental delay, 1 case by seizure onset, 1 case by attention-deficit/hyperactivity disorder, 1 case by autism spectrum symptoms, and 1 case by ventricular septal defect. Genetic testing has identified four heterozygous variants in the NAA15 gene, including one case with c.822_823insTA (p.E275*) nonsense variant, two cases with c.376_379delCAAAinsTCCTTACTACAGGT (p.Q126Sfs*9) frameshift variant caused by a complex indel, three cases with c.1029_1038delAGAGTTAGTA (p.E344*) nonsense variant, and one case with a c.692-5A>G splice-site variant. Functional analysis demonstrated that all variants has led to protein truncation. The c.692-5A>G variant may cause aberrant splicing. And the expression level of NAA15 mRNA in patients with the c.692-5A>G variant was significantly lower than the healthy controls. CONCLUSION:Variants of the NAA15 gene, including c.822_823insTA (p.E275*), c.376_379delCAAAinsTCCTTACTACAGGT (p.Q126Sfs*9), c.1029_1038delAGAGTTAGTA (p.E344*), and c.692-5A>G, may lead to MRD50. The core clinical manifestations are intellectual disability and language developmental delay, frequently accompanied by behavioral abnormalities and motor dysfunction.

ObjectiveThis study investigates the clinical features and genetic mutations associated with hyperphosphatasia with impaired intellectual development syndrome-2 (HPIDS2).MethodsA retrospective analysis was performed on two HPIDS2 cases treated at the Department of Rehabilitation, Nanjing Children's Hospital, from 2019 to 2023. Clinical features and genetic characteristics were summarized through a literature review.ResultsGenetic testing showed compound heterozygous variations in the PIGO gene for both patients (Patient 1: c.[2612A>C];[2361dup]; Patient 2: c.[2510T>A];[693C>G]), with c.[2510T>A] and c.[693C>G] identified as novel mutations.ConclusionGlobal developmental delay, with or without hyperphosphatemia, may indicate HPIDS2. The level of alkaline phosphatase elevation could reflect disease severity and prognosis. Our cases expand the known pathogenic variations in the PIGO gene and phenotypic spectrum of HPIDS2.

OBJECTIVE:To explore the clinical and genetic characteristics of a patient with Beck-Fahrner syndrome attributed to a TET3 gene variants. METHODS:A case of Beck-Fahrner syndrome (proband) who was treated at the Children's Hospital of Nanjing Medical University in December 2021 was selected as the study subject. Clinical data of the family were collected. Peripheral blood samples of the proband and his parents were collected, and genomic DNA was extracted for whole exome sequencing (WES). Candidate variants were verified in the family by Sanger sequencing. According to the "Classification Criteria and Guidelines for Genetic Variations" formulated by the American College of Medical Genetics and Genomics (hereinafter referred to as "ACMG guidelines"), the pathogenicity of the TET3 gene variant sites was rated. This study was approved by the Medical Ethics Committee of the Children's Hospital of Nanjing Medical University (Ethics No.: 202402022-1). RESULTS:The proband was a male, with a age of 9 months at the time of consultation. His clinical manifestations included decreased muscle tone, global developmental delay, long face, and open mouth. WES revealed that he has harbored a c.2811_c.2812insAGAC (p.T938fs*27) (NM_001287491) truncation variant in exon 7 of the TET3 gene. Sanger sequencing showed that neither of his parents has harbored the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION:The TET3 gene c.2811_c.2812insAGAC variant probably underlay the pathogenesis of Beck-Fahrner syndrome in the proband. Above discovery has enriched the mutational spectrum of the TET3 gene and provided a reference for the diagnosis and treatment of this disease.

BackgroundTo understand the reasons for hindering and promoting the recommended decision-making behaviors for early pulmonary rehabilitation of PICU medical staff, and to provide a basis for developing corresponding management plans.MethodsBased on the Capability, Opportunity, Motivation-Behavior (COM-B) model and Theoretical Domains Framework (TDF), interview outlines were developed. A descriptive qualitative research method was used, and a purposive sampling method was employed to select medical staff from the intensive care unit of a tertiary children's hospital in Nanjing from September to December 2023 for semi-structured interviews. The interview data were coded using the COM-B and TDF frameworks, and analyzed, summarized, and refined using the Colaizzi 7-step method to extract themes.ResultsFour main themes and 13 sub-themes were extracted, including the need for pulmonary rehabilitation knowledge and skills, the experience of implementing pulmonary rehabilitation in critically ill children, communication and collaboration in the PICU rehabilitation platform, and external support for PICU pulmonary rehabilitation.ConclusionIn the process of recommending early pulmonary rehabilitation for critically ill children, departments should help PICU medical staff change their views on pulmonary rehabilitation and acquire relevant knowledge and skills, strengthen multidisciplinary cooperation, optimize external support, and create a good practice environment for the implementation and promotion of early pulmonary rehabilitation for critically ill children.

IntroductionRehabilitation therapy is an important approach for spinal muscular atrophy (SMA) management. Currently, rare articles introduce that the combination of nusinersen and rehabilitation yields better results in SMA patients compared to using nusinersen alone. The present study examined whether rehabilitation therapy can improve the effectiveness of nusinersen and phosphorylated neurofilament heavy chain (pNF-H) and muscle magnetic resonance imaging (MRI) can serve as potential biomarkers for evaluating the therapeutic effects in type-2 SMA patients.MethodsThis observational study enrolled 22 pediatric patients with type-2 SMA. Enrolled patients were divided into two groups based on the rehabilitation treatment. Motor function and swallowing function were analyzed at baseline, 6, 10, and 14 months. The level of pNF-H and MRI of the thigh skeletal muscles were analyzed at baseline and 14 months.ResultsGreater improvement in motor function was observed in the rehabilitation group compared with the non-rehabilitation group. The levels of pNF-H in the serum and cerebrospinal fluid significantly decreased at 14 months. One patient from the rehabilitation treatment group showed mild improvement in the degree of fatty infiltration in the quadriceps muscles after 14 months.ConclusionThis study suggests that rehabilitation therapy improves the effectiveness of nusinersen on type-2 SMA patients, and the levels of pNF-H and skeletal muscle MRI can serve as potential biomarkers for evaluating the effectiveness of SMA treatment.

IntroductionVariants in the SR-related C-terminal domain-Associated factor 4 (SCAF4) gene are linked to Fliedner-Zweier syndrome (FZS), which presents with diverse symptoms, including mild intellectual disability, seizures, behavioral abnormalities, and various skeletal and structural anomalies. However, there is a paucity of cases describing genotypes and clinical features.Case presentationWe present the case of a 4-year and seven-month-old Chinese boy displaying intellectual impairment, language development disorder, behavioral abnormalities, and distinct facial features. Whole exome sequencing (WES) identified a heterozygous nonsense mutation, c.1693C>T (p.Arg565*), located in exon 14 of the SCAF4 gene (NM_020706). Sanger sequencing confirmed paternal inheritance of this mutation. RNA sequencing from the patient demonstrated widespread transcriptional dysregulation, reinforcing the role of SCAF4 dysfunction in impaired transcription and neurodevelopmental disorders. This mutation is novel, not previously recorded in databases such as GnomAD or dbSNP, nor reported in existing literature.ConclusionWe reviewed the clinical features of the patients reported in the literature with mutations in SCAF4 gene and described the case of a Chinese patient with this mutation. This case underscores the critical need for continued exploration of genotype-phenotype correlations, enhancing our understanding of the diverse manifestations of Fliedner-Zweier syndrome and informing future diagnostic and therapeutic strategies.

The quest for effective treatments for cerebral palsy (CP) remains a significant challenge, crucial for improving outcomes in affected individuals. This study aimed to evaluate the therapeutic effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) on lower limb function in children with hemiplegic cerebral palsy (HCP) through a controlled clinical trial. Forty children with HCP were randomly assigned to either a sham stimulation group or an rTMS treatment group, with 20 participants in each. The rTMS group received low-frequency rTMS in conjunction with conventional rehabilitation, while the sham group received sham stimulation paired with the same rehabilitation. Conventional rehabilitation included physical therapy, occupational therapy, orthopedic shoes, acupuncture, and other training modalities. Treatments were administered 5 days a week for 12 weeks. We assessed gross and fine motor skills, spasticity, and gait parameters before and after treatment using the modified Ashworth scale (MAS), dorsiflexion angle, gross motor function measure 88 (GMFM-88), Gesell developmental scale, and plantar pressure gait analysis. After 12 weeks, both groups exhibited improvements in MAS scores of the affected hamstring muscle, dorsiflexion angles, GMFM-88 D and E zone scores, Gesell developmental scale scores (gross motor), and gait parameters ( P < .05). Notably, the rTMS group demonstrated significantly greater improvements ( P < .05). Low-frequency rTMS combined with conventional rehabilitation therapy leads to better outcomes in gross and fine motor functions while reducing spasticity and improving gait parameters in children with HCP compared to sham stimulation.

AIM:To investigate the independent influences affecting the global score of the Hammersmith Infant Neurological Examination (HINE) in the early life of high-risk infants and to provide evidence for early effective screening and for evaluating interventions. METHOD:We conducted a prospective cohort study of 258 high-risk infants assessed by the HINE and Gesell Developmental Diagnosis Schedule at 3, 6, 9, and 12 months corrected age. A multiple linear regression model was developed to investigate independent influences on HINE global score at 3 months corrected age. The accuracy of the HINE global score was analysed by calculating the discriminant, concurrent, and predictive validities according to ages. RESULTS:There were nine independent influences affecting the HINE global score at 3 months corrected age in high-risk infants. The discriminant, concurrent, and predictive validities of the HINE for gross motor developmental delays at 12 months corrected age were all statistically significant (p < 0.05). INTERPRETATION:Different neonatal clinical settings are related to the HINE global score of high-risk infants early in life. The HINE can be used for longitudinal monitoring of neurological development in the first year of life in a typical Chinese clinical setting and the findings at all four ages tested relate to neuromotor outcomes at 12 months corrected age.

Objective To analyze the clinical and genetic characteristics of three children with congenital heart defects,dysmorphic facial features and intellectual developmental disorders(CHDFIDD).Methods Three children presenting with CHDFIDD were enrolled.Genomic DNA was extracted from peripheral venous blood of the children and their parents.Whole-exome sequencing(WES)was performed using chip-capture high-throughput sequencing technology.Suspected causative mutations were verified by Sanger sequencing and bioinformatic analysis.Using"CDK13 gene"and"CDK13-related diseases"as search terms,literatures of CNKI and Wanfang database were retrieved until February 2024.Using"CDK13","CDK13-related disorder"and"CHDFIDD"as search terms,literatures from the establishment of PubMed database untio February 2024 was retrieved,and the relevant literature was reviewed.Results WES revealed heterozygous variants of the CDK13 gene in three children,including c.2572 C>T(p.Leu858Phe),c.2579 G>A(p.Arg860Gln),and c.2602C>T(p.Arg868Trp),which were verified as de novo variants by Sanger sequencing.Combined with the clinical phenotype,all 3 children were diagnosed with CHDFIDD.However,the possibility that one of the affected children's parents was a germline chimera for the mutation could not be excluded.According to the ACMG guidelines,all three mutation sites were classified as likely pathogenic.A total of 14 studies consisting of 108 cases were retrieved.Among them,c.2572C>T has not been reported.Conclusions The de novo variants of the CDK13 gene may be the genetic cause of developmental delay/intellectual disability in these three children.The findings in the present study expand the spectrum of CDK13 gene mutations,providing reference for the diagnosis of CHDFIDD.

Emerging research has demonstrated that genomic alterations disrupting topologically associated domains (TADs) and chromatin interactions underlie the pathogenic mechanisms of specific copy number variants (CNVs) in neurodevelopmental disorders. We report two patients with a de novo deletion and a duplication in chromosome 4q31, potentially causing FBX-related neurodevelopmental syndrome by affecting the regulatory region of FBXW7. High-throughput chromosome conformation capture (Hi-C) analysis using available capture data in neural progenitor cells revealed the rewiring of the TAD boundary close to FBXW7. Both patients exhibited facial dysmorphisms, cardiac and limb abnormalities, and neurodevelopmental delays, showing significant clinical overlap with previously reported FBXW7-related features. We also included an additional 10 patients with CNVs in the 4q31 region from the literature and the DECIPHER database for Hi-C analysis, which confirmed that disruption of the regulatory region of FBXW7 likely contributes to the developmental defects observed in these patients.

Chloride voltage-gated channel, as an important ion channel in living organisms, has many important physiological functions.The gene encoding chloride voltage-gated channel protein is CLCN, which has nine members(CLCN1~7, CLCNKa, and CLCNKb).The CLCN gene variants lead to abnormal expression of chloride channel proteins, which affect the biological activities of neuronal signaling, ion homeostasis, intracellular transport, and lysosomal protein degradation, thereby altering ion channel gating properties, interfering with the normal developmental process of the nervous system, and causing the development of intellectual disability.In recent years, further studies of the CLCN gene have found that the variants in some members of this family are closely related to intellectual disability.This review will discuss the correlation between the chloride voltage-gated channel and intellectual disability.

Biallelic TENM3 variants were recently reported to cause non-syndromic microphthalmia with coloboma-9 (MCOPCB9) and microphthalmia and/or coloboma with developmental delay (MCOPS15). To date, only eight syndromic and non-syndromic microphthalmia cases with recessive TENM3 variants have been reported. Herein, we report two unrelated new cases with biallelic variants in TENM3, widening the molecular and clinical spectrum. Regarding patient 1, WES revealed compound heterozygous variants in the TENM3 gene: c.3847_3855del; p.Leu1283_Ser1285del and c.3698_3699insA; p.Thr1233Thrfs*20 in the index patient, who was presenting with bilateral microphthalmia, congenital cataract, microcephaly, and global developmental delay. Regarding patient 2, compound missense heterozygous variants in the TENM3 gene were identified: c.941C > T; p.Ala314Val and c.6464T > C; p.Leu2155Pro in the 3-year-old boy, who presented with congenital esotropia, speech delay, and motor developmental delay. The clinical features of these two cases revealed high concordance with the previously reported cases, including microphthalmia and developmental delay. The presence of microcephaly in our patient potentially expands the neurologic phenotype associated with loss of function variants in TENM3, as microcephaly has not previously been described. Furthermore, we present evidence that missense variants in TENM3 are associated with similar, but milder, ocular features.

OBJECTIVES:Microcephaly is caused by reduced brain volume and most usually associated with a variety of neurodevelopmental disorders (NDDs). To provide an overview of the diagnostic yield of whole exome sequencing (WES) and promote novel candidates in genetically unsolved families, we studied the clinical and genetic landscape of an unselected Chinese cohort of patients with microcephaly.METHODS:We performed WES in an unselected cohort of 103 NDDs patients with microcephaly as one of the features. Full evaluation of potential novel candidate genes was applied in genetically undiagnosed families. Functional validations of selected variants were conducted in cultured cells. To augment the discovery of novel candidates, we queried our genomic sequencing data repository for additional likely disease-causing variants in the identified candidate genes.RESULTS:In 65 families (63.1%), causative sequence variants (SVs) and clinically relevant copy number variants (CNVs) with a pathogenic or likely pathogenic (P/LP) level were identified. By incorporating coverage analysis to WES, a pathogenic or likely pathogenic CNV was detected in 15 families (16/103, 15.5%). In another eight families (8/103, 7.8%), we identified variants in newly reported gene (CCND2) and potential novel neurodevelopmental disorders /microcephaly candidate genes, which involved in cell cycle and division (PWP2, CCND2), CDC42/RAC signaling related actin cytoskeletal organization (DOCK9, RHOF), neurogenesis (ELAVL3, PPP1R9B, KCNH3) and transcription regulation (IRF2BP1). By looking into our data repository of 5066 families with NDDs, we identified additional two cases with variants in DOCK9 and PPP1R9B, respectively.CONCLUSION:Our results expand the morbid genome of monogenic neurodevelopmental disorders and support the adoption of WES as a first-tier test for individuals with microcephaly.

Objective The dysfunction of the CLCN4 gene can lead to X-linked intellectual disability and Raynaud–Claes syndrome (MRXSRC), characterized by severe cognitive impairment and mental disorders. This study aimed to investigate the genetic defects and clinical features of Chinese children with CLCN4 variants and explore the effect of mutant ClC-4 on the protein expression level and subcellular localization through in vitro experiments. Methods A total of 401 children with intellectual disabilities were screened for genetic variability using whole-exome sequencing (WES). Clinical data, including age, sex, perinatal conditions, and environmental exposure, were collected. Cognitive, verbal, motor, and social behavioral abilities were evaluated. Candidate variants were verified using Sanger sequencing, and their pathogenicity and conservation were analyzed using in silico prediction tools. Protein expression and localization of mutant ClC-4 were measured using Western blotting (WB) and immunofluorescence microscopy. The impact of a splice site variant was assessed with a minigene assay. Results Exome analysis identified five rare CLCN4 variants in six unrelated patients with intellectual disabilities, including two recurrent heterozygous de novo missense variants (p.D89N and p.A555V) in three female patients, and two hemizygous missense variants (p.N141S and p.R694Q) and a splicing variant (c.1390-12T > G) that are maternally inherited in three male patients. The p.N141S variant and the splicing variant c.1390-12(T > G were novel, while p.R694Q was identified in two asymptomatic heterozygous female patients. The six children with CLCN4 variants exhibited a neurodevelopmental spectrum disease characterized by intellectual disability (ID), delayed speech, autism spectrum disorders (ASD), microcephaly, hypertonia, and abnormal imaging findings. The minigene splicing result indicated that the c.1390-12T > G did not affect the splicing of CLCN4 mRNA. In vitro experiments showed that the mutant protein level and localization of mutant protein are similar to the wild type. Conclusion The study identified six probands with CLCN4 gene variants associated with X-linked ID. It expanded the gene and phenotype spectrum of CLCN4 variants. The bioinformatic analysis supported the pathogenicity of CLCN4 variants. However, these CLCN4 gene variants did not affect the ClC-4 expression levels and protein location, consistent with previous studies. Further investigations are necessary to investigate the pathogenetic mechanism.

常染色体显性遗传脊髓性肌萎缩症-下肢1型(spinalmuscular atrophy,lowerextremitypredominant-1, SMALED1)是一种非常罕见的、因DYNC1H1基因杂合性突变导致的常染色体显性遗传病.2010年, Harms等[1-2]根据染色体14q32连锁显性遗传与主要表现为下肢远端受累脊髓性肌萎缩症的临床特征,提出了SMALED1的命名,并在随后的研究中鉴定了DYNC1H1基因杂合性突变为SMALED1的遗传性病因.

Objective:To explore any effect of orofacial myofunction therapy (OMT) on the swallowing and speech of children with Pierre-Robin malformation (PRS) after a corrective operation.Methods:Fifty-two children with dysphagia caused by PRS mandibular distraction osteogenesis were randomly divided into an observation group and a control group, each of 26. All were given routine nutrition support, but the observation group was additionally provided with OMT. Swallowing disorders, nutritional risk and body mass index were compared between the two groups after 6 months of the intervention. Orofacial muscle functioning and speech and language disorders were also compared between the two groups at the age of 3.Results:After the 6-month intervention the average Ichiro Fujishima dysphagia score in the observation group had improved significantly compared with before treatment and with the control group. The observation group′s nutritional status was also significantly better. At age three the orofacial myofunction classification of the observation group remained significantly better, on average, than that in the control group, and dysarthria or language retardation was significantly less prevalent.Conclusion:OMT can significantly improve the swallowing function, speech and nutritional status of children after surgery to correct PRS. This therapy is worthy of promotion and clinical application.

Objective:To observe the effect of oral-facial muscle training applying virtual reality technology (VR) and of action observation therapy on the salivation of children with cerebral palsy (CP).Methods:Sixty CP children with uncontrolled salivation were randomly divided into a control group and an observation group, each of 30. In addition to conventional rehabilitation treatment, the control group received routine tongue muscle training, buccal lip muscle training, ice stimulation, and Masako swallowing training. The observation group received oral-facial muscle training based on action observation therapy in a virtual environment. Both groups were trained 30min per day, 5 times a week for 3 weeks. Before and after the treatment, drooling (DDSS) and swallowing function scores were evaluated. Integrated surface electromyography (iEMG) of the buccinator and orbicularis oris muscles was also performed.Results:After treatment, a significant decrease was observed in the average DDSS and the swallowing function scores of both the control and observation groups, along with a significant increase in the average root mean square values of the buccinator and orbicularis oris iEMGs of both groups. However, the average DDSS score of the observation group was significantly lower than that of the control group, while the average iEMG readings were significantly better.Conclusion:VR-based action observation oral-facial muscle training is a more effective supplement to conventional rehabilitation treatment than conventional oral-facial muscle training in improving the salivation of children with CP.

Objective:To explore the ability of the Hammersmith Infant Neurological Examination (HINE) to predict the gross motor development of high-risk infants.Methods:A total of 207 high-risk infants were assessed with the HINE and the Gesell Developmental Schedule (GDS) at the ages of 3, 6, 9 and 12 months. They were then divided into a normal development group and a delayed group according to their gross motor development at 12 months old. The validity of the HINE′s discrimination was quantified retrospectively as the difference in the total HINE score at each follow-up month between the two groups. Spearman coefficients relating the total HINE score with the gross motor development quotient from the GDS were calculated at each follow-up month. The HINE′s total score threshold for predicting gross motor retardation at 12 months was determined from a receiver operating characteristics curve, and the predictive validity, sensitivity and specificity were evaluated by calculating the area under the curve.Results:At each time point the average total HINE score of the delayed group was significantly lower than the normal group′s average. The correlation between the HINE total scores and the GDS gross motor development quotients was strongest at 6 months old, and weakest at 3 months. The threshold total HINE score for predicting gross motor retardation at 12 months old was 60 at 3 months, 67 at 6 months, and then 71. The instrument′s sensitivity and specificity were very good at all four time points.Conclusion:The HINE can usefully predict gross motor retardation in the first year of life for high-risk infants. The critical value of the total score can be used as an auxiliary diagnostic reference for neuromotor development in such infants.