Autism and Mental Retardation of Young Children in China

To understand the prevalence and rehabilitation status of autism and mental retardation in China. Methods Screening test and clinical assessment were conducted for the diagnosis of autism and mental retardation. The assessment included investigation of the histories of medical conditions and development of these two disorders, utilization and needs for the rehabilitation service, and related intellectual and behavioral appraisal. Results Among the 7345 children investigated, the prevalence of autism disorder was 1.10 cases per 1000 children aged 2-6 years （95% CI=0.34 to 2.54）, and the prevalence of mental retardation was 10.76 cases per 1000 children （95% CI=8.40 to 13.12）. All the children suffering from autistic disorder were intellectually disabled, whereas 31.0% of the non-autism mental retardates had other disabilities. The medical conditions prior to birth and perinatal period were important potential factors for autism. Half of the autistic children and 84% of the children with non-autism mental retardation had never received any rehabilitative service. Conclusions The prevalence of autistic disorder in children aged 2-6 years in Tianjin is rather high. It is urgent to improve the status of the autistic and intelligently disabled young children in China. In order to upgrade the level of early diagnostic and improve the intervention to autism and mental retardation, public awareness and training courses should be heightened.

Autism with dysphasia accompanied by mental retardation caused by FOXP1 exon deletion:A case report

BACKGROUND Forkhead box protein 1(FOXP1)(OMIM:605515)at chromosomal region 3p14.1 plays an important regulatory role in cell development and functions by regulating genetic expression.Earlier studies have suggested that FOXP1,an oncogene,is capable of initiating tumorigenicity depending on the cell type.FOXP1 also plays an important role in regulating the cell development and functions of the immune system,e.g.,regulating B-cell maturation and mononuclear phagocyte differentiation,and in the occurrence and development of various immune diseases.The mRNA of this gene is widely expressed in humans,and its differential expression is related to numerous diseases.CASE SUMMARY A 5-year-old boy mainly presented with attention deficit and hyperactivity disorder and developmental retardation accompanied by gait instability and abnormal facial features(low-set ears).DNA samples were extracted from the child’s and his parents’peripheral blood to detect whole-exome sequences and whole-genome copy number variations.Results revealed heterozygous deletions of exon 6-21 of FOXP1 gene in the child.Physical examination upon admission showed that the child was generally in good condition,had a moderate nutritional status,a slightly slow response to external stimuli,equally large and equally round bilateral pupils,was sensitive to light reflection,and had poor eye contact and joint attention.He had no meaningful utterance and could not pronounce words properly.He was able to use gestures to simply express his thoughts,to perform simple actions,and to listen to instructions.He had no rash,cafe-au-lait macules,or depigmentation spots.He had thick black hair and low-set ears.He had highly sensitive skin,especially on his face and palms.He had no abnormal palm fingerprint.Cardiopulmonary and abdominal examinations revealed no abnormalities.He had normal limb muscle strength and tension.He showed normal tendon reflexes of both knees.His bilateral Babinski and meningeal irritation signs were negative.He had a normal male vulva.CONCLUSION We report the characteristic features of autism with dysphasia accompanied by mental retardation caused by FOXP1 exon deletion.This study provides a molecular basis for etiological diagnosis and treatment of the child,as well as for genetic counseling for the pedigree.

GABAB receptor upregulates fragile X mental retardation protein expression in neurons

Aim Fragile X mental retardation protein （FMRP） is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome （FXS） , which leads to intellectual disability and social impairment. γ-aminobutyric acid （GABA） is the major inhibitory neuro- transmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation. Here we investi- gated the signaling events linking the GABAB receptor and FMRP. Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons. For key molecules in signal- ling pathway, RNAi was used in MEFs to confirm the results in neurons. Results GABAB receptor activation up- regulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms： the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a po- tential interest of GABAB receptor signaling in FXS improvement.

Correlating fine motor function to cognitive competence in children with mental retardation An analysis of 42 cases

BACKGROUND： In clinical practice, the degree of cognitive competence damage correlates to fine motor function deficits in children with psychomotor development retardation. Clear correlations between the two can help to develop and perform corresponding functional training for children with mental retardation （MR）. OBJECTIVE： This study was designed to evaluate and analyze the correlation of fine motor function to cognitive competence in MR children using the Peabody Developmental Motor Scale-Fine Motor （PDMS-FM） and Symbolic Play Test. DESIGN： Scale evaluation and correlation analysis. SETTING： Children＇s Rehabilitation Center ＆ Huajing District Hospital, Children＇s Hospital Affiliated to Fudan University. PARTICIPANTS： A total of 42 MR children, 28 males and 14 females, aged 14-69 months, were admitted to the Rehabilitation Center, Children＇s Hospital, Fudan University between June 2003 and April 2006, and were recruited for this study. All children corresponded to MR diagnosis criteria determined by Chinese Neurology and Psychiatry Society in 1989. Written informed consent for participating in the evaluation and for evaluated content was obtained from each child＇s guardian. METHODS： Subsequent to admission and prior to treatment, fine motor function of each MR child was evaluated using PDMS-FM （Chinese version）. The scale captured 98 items that formed the grasping （Gr） and visual-motor integration （Vi） subtests. Cognitive competence was evaluated using the Symbolic Play Test （Chinese version）, which captured four 6-item specific contents. The original score of each subtest was used to evaluate results for statistical analysis. Higher scores from the two evaluations indicated stronger abilities. Pearson correlation analysis was applied for analyzing data correlation. MAIN OUTCOME MEASURES： Fine motor function was evaluated using PDMS-FM. Cognitive competence was measured using the Symbolic Play Test. Correlations between results from the two evaluations were analyzed. RESULTS： All 42 MR children were included in the final analysis. Correlation analysis results demonstrated significant positive correlations of original scores existed between Gr and Vi subtests in the PDMS-FM （r = 0.761, P 〈 0.01）, and between Vi and Gr subtests in PDMS-FM and Symbolic Play Test （r = 0.663, 0.450, P 〈 0.01）. CONCLUSION： Fine motor function closely correlates to cognitive competence in MR children. This indicates fine motor function training should be developed in combination with cognitive competence training.

Molecular Genetic Analysis of Partial 9p Trisomy in Two Chinese Families with Mental Retardation and Facial Anomaly

Mental retardation is defined by significant limitations in intellectual function and adaptive behavior that occur before 18 years of age.Many chromosomal diseases come with mental retardation.We reported two Chinese families with partial trisomy 9p and other chromosome partial monosomy,clinical features of mental retardation and mild facial and pinkie anomalies.In the family 1,we showed that the proband carried a trisomy 9p21.3→pter and monosomy 21q22.3→qter by using fluorescence in situ hybridization analysis.Molecular genetic analysis defined the precise breakpoint on chromosome 9p between markers D9S1846 and D9S171,an interval of about 2.9 Mb on 9p21.3,and the breakpoint on chromosome 21q between markers D21S1897 and D21S1446,a region of about 1.5 Mb on 21q22.3.In the family 2,a patient with trisomy 9p21.3→pter and monosomy 5p15.33→pter,and a de novo maternal balanced translocation between chromosomes 5 and 9 was identified in his mother.Cytogenetic and molecular genetic analysis defined the precise breakpoints on chromosome 9p21.3 and chromosome 5p15.33.Further clinical investigation found that any individual had no refractoriness eczema disease except the proband in this family.These results further implicate that trisomy 9p is associated with mental retardation,and that there may be key gene duplication on chromosome 9p21.3→9pter responsible for mental retardation and mild facial anomaly.This result has been applied successfully in prenatal diagnosis of the second family.

Primed In Situ Labeling Technique for Subtelomeric Rearrangements in 70 Children with Idiopathic Mental Retardation

Subtelomeric rearrangements contribute to idiopathic mental retardation （MR）, but most children with idiopathic MR do not show any chromosome abnormalities with standard cytogenetic analysis. The primed in situ labeling （PRINS） technique, using an oligonucleotide primer complementary to the telemetric repeat sequences （TTAGGG）, can identify chromosome telomeric abnormality （deletion） in idiopathic MR children. In this study, seventy children with idiopathic MR were enrolled and subjected to PR1NS. The results showed normal karyotype in all the children, subtelomeric rearrangements （lq del and 4q del） in 2 cases, which was confirmed by fluorescence in situ hybridization （FISH）. It was concluded that PRINS is effective for the detection of subtelomeric rearrangements and may become a routine technique for cytogenetical abnormality screening.

A STUDY ON CNV OF PATIENTS WITH MENTAL RETARDATION

Objective: To investigate the variations of contingent negative variation (CNV) of petients with mental retardation. Methods: The CNV was recorded in 16 children with mental retardation (MR) and 14 healthly age-matched controls. And CNV retest was carried out in 11 children with MR after one yeat treatment of Piracetam. Results: Compared with the normal control, the CNV of MR group showed prolonged postimperative negative variation (PINV) duration (P＜0.01) and total A-C duration (P ＜ 0.01), decreased amplitude B (P＜0.01 ), and reduced preimperative A-S2 area (P＜0.01). A comparison of the CNV of MR group was made between before and after one year treatment of Piracetam and no significant difference was found. Conclusions:The significant CNV variations were found in children with MR and these abnormal changes presisted throughout the Piracetam treatment.

Periodontal Tissue Status among Mental Retardation Patients with Fixed Prosthodontic Appliances

Background: The mental, physical and social impediments cause limitation of chances in normal life as an equal level with others of the community;particularly in relation to maintain good oral hygiene and periodontal health among the disabled patients who were receiving fixed partial denture. So the present study was performed to evaluate the periodontal tissue status among mental retardation patients with fixed prosthodontic appliances. Subjects and Methods: A total of 400 patients between the ages 18 and 50 years were clinically selected from outpatient clinics, college of dentistry, King Khalid University and rehabilitation center in Abha city, Saudi Arabia. They were divided into two equal groups as the following: group I: Two hundred mental retardation patients without fixed prosthodontic appliances (control group) and, group II: Two hundred mental retardation patients had fixed prosthodontic appliances for at least a year ago. A complete periodontal clinical examination was performed and the following indices were recorded: plaque index (PLI), gingival index (GI), and clinical attachment loss (CAL). All data was recorded and analyzed by ANOVA test. Results: The clinical results of the present study confirmed the relationship among the mental retardation, fixed prosthodontic appliances and destruction of periodontal tissues. It has been found that the severity of periodontal disease increases among the study group compared to the control group. Statistically significant differences were found in PLI, GI and CAL in the comparison between group I and II (p Conclusion: There was a negative relationship between mental retardation with a status of periodontal tissues and oral hygiene among the patients under fixed prosthodontic management.

Prevalence of Mental Retardation in Children of Shimoga District—An Overview

Background: Mental retardation is an important condition in children. People in the community need to be aware of the presence, need to act and prevent this problem. Mental retardation means mental growth of the child is not at par with physical growth. Mental retardation is calculated as intelligence quationent. (IQ) = Mental age/chronological age × 100. There are causes and can be categorized as prenatal, natal and postnatal factors. Mental retardation is classified as Mild Mental retardation IQ of 51 - 70;Moderate Mental retardation IQ of 36 - 50;Severe Mental retardation IQ of 21 - 35;Profound Mental retardation IQ of less than 20. IQ of 71 - 89 is designated as borderline mental retardation. Objectives: Analyzing the procured data creates awareness in the society regarding mental retardation and its burden to the society. Results: The analysis is done using the data provided from the office of Deputy Director, Department of Public Instruction, Sarvashikshana Abhiyana (SSA) Shimoga District [1]. 555 children were having mental retardation ranging from mild to profound severity. The total number of children with various disabilities was 1185, mental retardation alone was nearing 50% of the total disabilities. Conclusion: 50% of total disability was found to be mental retardation which needs to proliferate.

Improvement of mental retardation plus epilepsy in children following management

Objective To investigate the effective management approaches for mental retardat ion plus epilepsy in children.Method Sodium valproat 15～60mg /(kg·day)or nitrazepam0.5～1mg /(kg·day)and guanmaishu containing hyoscyam ine(0.0045～0.045mg /(kg·day)as adjuvant were administered for 1.5～2consecutive years.EEG,three di mensional Doppler ultrasonic exami nation of cerebral vessels were performed.Result Favorable therapeutic effect was obtained in 25cases(48.1%),good effect in 12cases(23.1%).Conclusion Favorable therapeutic effect of hyoscyamine i n epilepsy is correlated with improved cerebral microcirculation,cortical choline receptor blocking ,red uced con-duction between synapses.These factors all inhibit onset of epilepsy.

INFLUENCE OF ACUPUNCTURE ("JIN'S SAN ZHEN") ON BRAINSTEM EVOKED POTENTIALS IN MENTAL RETARDATION CHILDREN

Objective: To investigate the effect of acupuncture ("JIN’s San Zhen") on infantile mental retardation (MR). Methods: 44 cases of MR children were attributed to treatment group and 39 normal children to control group. P 3 (event related potential) and brainstem evoked potentials were used as the indexes. Acupoints "Si shen Zhen", "Head Zhi San Zhen", "Hand Zhi San Zhen", "Foot Zhi San Zhen" were punctured with filiform needles, and stimulated by manipulating the needle once every 5 minutes with uniform reinforcing reducing method. The treatment was conducted once daily, 6 times every week, with 4 months being a therapeutic course. Results: In comparison with normal children, the latency of P 3 was longer and its amplitude lower in MR children. After 4 months’ acupuncture treatment, the latency was shortened and the amplitude increased significantly in comparison with pre treatment (P<0.01, 0.05). Results of the total intelligence quotient (TIQ) evaluation showed a 70.3% coincidence rate compared with improvement of P 3. Conclusion: Changes of P 3 and BAEP(brain auditory evoked potential) after acupuncture treatment may be related to the effect of "JIN’s San Zhen" in bettering clinical symptoms and signs of MR infantile patients.

CNKSR2 mutation causes the X-linked epilepsy-aphasia syndrome:A case report and review of literature

The mutation in CNKSR2 leads to a broad spectrum of phenotypic variability and manifests as an X-linked intellectual disability. However, we reported that the male patient in this study not only had intellectual disability but also epileptic seizures. In addition, there were progressive language impairment, attention deficit hype-ractivity disorder and autism. Electroencephalograms showed continuous spike-and-wave during sleep. Genetic testing revealed a de novo mutation of the CNKSR2 gene(c.2185C >T, p.Arg729Ter) in the child that was not detected in the parents. Therefore, the child was diagnosed with X-linked epilepsy aphasia syndrome. Deletion of the CNKSR2 gene has been rarely reported in epilepsy aphasia syndrome, but no de novo mutation has been found in this gene. This report not only adds to the spectrum of epilepsy aphasia syndrome but also helps clinicians in diagnosis and genetic counseling.

Prevalence of Strongyloides stercoralis and other intestinal parasitic infections among mentally retarded residents in central institution of southern Iran

Objective:To determine the prevalence of intestinal parasitic infections among mentally retarded residents of rehabilitation center of Bandar Abbas,Hormozgan province,southern Iran.Methods:A cross-sectional study was carried out in central rehabilitation institute of Hormozgan province in summer 2010.Fecal samples of all 133 residents(72 males,61 females)aged 3-52,were collected in triplicate.Specimens were examined by direct smear,formalin-ether concentration techniques and stained by permanent Trichrome,Ziehl-Neelsen stains.Statistical analysis was conducted by SPSS 13.5.Results:Intestinal parasitic infections were seen in 48.5%(64 out of 133 subjects:53.4%in males and 46.6%in females).Strongyloides stercoralis with17.3%showed the highest incidence followed by Entamoeba coli(9.8%),Blastocystis hominis(7.5%),Giardia lamblia(2.3%),Endolimax nana(2.3%),Hymenolepis nana(0.8%),Oxyuris vermicularis(0.8%),and Chilomasix mesnili(0.8%).Double infections were found to be as:Strongyloides stercoralis+Giardia lamblia(2.3%),Entamoeba coli+Giardia lamblia(1.5%),Entamoeba coli+Blastocystis hominis(1.5%),Oxyuris vermicularis+Entamoeba coli(0.8%),Strongyloides stercoralis+Entamoeba coli(0.8%),respectively.Conclusions:Our findings reveal that strongyloidiasis is a common disease among mentally retarded population in southern Iran.

On the Lawful Rights and Interests of Mentally Retarded Children——A case study of a rehabilitation center in Liaoning Province

Mentally retarded children are the most disadvan- taged among disabled children. Since the reform and opening up, with sup- port from the Communist Party of China, the government and the public, the legitimate rights and interests of mentally retarded children have greatly improved. But problems in this respect remain serious, and vari- ous levels of government, relevant departments and the public should attach much importance to these problems. This paper, taking a reha- bilitation center in Liaoning Province for mentally retarded children as a single case, studies the protection of these children＇s lawful rights and in- terests in a systematic manner.

郭氏背三针结合头针丛刺法治疗智力障碍/全面发育迟缓儿童的疗效观察

目的 观察郭氏背三针结合头针丛刺法治疗智力障碍/全面发育迟缓儿童的疗效。方法 选取2022年4月至2023年8月河南省中医院收治的70例全面发育迟缓或智力障碍患儿,采用随机数字表法,将患者分成试验组和对照组,每组各35例,对照组仅给予头针丛刺法配合常规康复训练,试验组在对照组基础上给予郭氏背三针治疗。比较治疗前后儿童神经心理发育量表(Gesell)评分发育商、韦氏儿童智力测试(WISC)评分、婴儿-初中生社会生活能力量表(S-M)评分及脑血流动力学指标[脑动脉平均血流速度(Vm)、收缩期峰流速度(Vs)、血管阻力指数(RI)及血管搏动指数(PI)],比较两组临床疗效和不良事件发生情况。结果 试验组治疗后总有效率(91.43%)较对照组(71.43%)高(P<0.05);治疗后Gesell评分各发育商、WSIC各评分及(≥5岁和<5岁)的S-M评分均较治疗前高,且试验组较对照组高(P<0.05);治疗后Vm、Vs、PI均较治疗前高,且试验组较对照组高(P<0.05);治疗后RI较治疗前低,且试验组较对照组低(P<0.05);两组不良事件发生率比较差异无统计学意义(P>0.05)。结论 郭氏背三针结合头针丛刺法治疗智力障碍/全面发育迟缓儿童疗效明显,可提高儿童的神经发育、智力发育及生活能力,改善脑血流动力学,且有良好的安全性。

低频经颅磁刺激联合早期康复训练在伴智力低下孤独症谱系障碍患儿中的应用

目的探究低频经颅磁刺激(TMS)联合早期康复训练治疗伴智力低下孤独症谱系障碍(ASD)患儿的效果。方法选取南阳市第一人民医院2018年2月至2022年9月收治的104例伴智力低下ASD患儿,按随机数字表法分成两组,每组52例。以接受早期康复训练的52例伴智力低下ASD患儿列为B组,以接受低频TMS联合早期康复训练的52例伴智力低下ASD患儿列为A组。对比两组治疗前后孤独症行为评定量表(ABC)评分、中国韦氏儿童智力量表(C-WISC)评分、儿童感觉统合评定量表(CSIRS)评分、事件相关电位(ERP)P3潜伏期、波幅、神经递质[γ-氨基丁酸(GABA)、谷氨酸(GLU)、5-羟色胺(5-HT)、脑源性神经营养因子(BDNF)]水平。结果治疗6个月后A组感觉、交往、躯体运动、语言、生活自理评分较B组低(P<0.05);治疗6个月后A组言语智商、操作智商及总智商评分较B组高(P<0.05);治疗6个月后A组学习能力、触觉防御、本体感觉、前庭失衡评分较B组高(P<0.05);治疗6个月后A组ERP P3潜伏期较B组低,波幅较B组高(P<0.05);治疗6个月后A组血清GLU、5-HT、BDNF水平较B组低,血清GABA水平较B组高(P<0.05)。结论低频TMS联合早期康复训练治疗伴智力低下ASD患儿可进一步改善行为能力,提升智力水平,改善感觉统合能力,维持中枢神经系统内环境平衡。

Sin3A基因变异致Witteveen-Kolk综合征遗传学分析

目的 探讨开关不敏感3转录调节因子家族成员A(Sin3A)基因变异导致的Witteveen-Kolk综合征临床表型和遗传学特点。方法 收集1例发育迟缓患儿的临床资料,对患儿及其父母进行全外显子基因测序,采用Sanger测序验证可疑变异,并进行家系分析。结合文献分析Witteveen-Kolk综合征的临床特征和基因变异特点。结果 Witteveen-Kolk综合征患儿临床表现主要为轻中度智力障碍或发育迟缓、特殊面容(长脸、前额突出、鼻梁凹陷、长人中等)、身材矮小。颅脑磁共振成像(MRI)显示不同程度的脑畸形。全外显子基因测序结果显示,患儿Sin3A基因存在移码变异c.803dupC(p.Leu269Thrfs*37)(杂合)。Sanger测序证实存在变异位点,患儿父母该位点均为正常基因型。gnomAD等对照人群数据库未收录该变异位点,根据美国医学遗传学和基因组学学会(ACMG)/美国分子病理学学会(AMP)指南归类为“致病性”变异。结论 Sin3A基因变异可导致Witteveen-Kolk综合征。基因检测可明确生长发育迟缓伴特殊面容患儿的病因。

伴有癫痫的脆性X综合征家系1例

脆性X综合征(fragile X syndrome,FXS)是FMR1基因CGG异常重复扩增导致的疾病。本文报告1对经基因检测诊断为FXS的兄弟,2例患者分别为15岁和14岁,均存在语言障碍、智力障碍、注意力缺陷障碍、孤独症谱系障碍和FXS特征性面容等临床表现,其中先证者伴有罕见的晚发性癫痫发作,经左乙拉西坦治疗效果良好,而其弟弟经反复随访未见脑电图异常。该对病例提示FXS临床表型具有多样性和异质性。

精神发育迟滞伴精神障碍患者的外科治疗手段及疗效

精神发育迟滞(mentalretardation,MR)患者常表现为智力低下和社会生活适应困难,也可伴有精神障碍、行为障碍、以及情感障碍等其他症状。MR在我国城乡精神疾病中占比较大,属于预防与治疗的重点疾病,是一种难治性精神疾病。精神发育迟滞患病人群年龄较小,在幼年即可发病,相关症状往往伴随终生。精神发育迟滞主要由遗传因素及环境因素导致,患者存在多种躯体和神经系统疾病,伴有行为异常、社会适应能力差等症状。MR可根据IQ值及严重程度分为轻、中、重、极重四级,常用婴儿-初中生社会生活能力量表及格塞尔发展量表、创伤筛选问卷、智力残疾儿童学习能力评估表、简明曼彻斯特生存质量评定量表进行评估。目前常用的外科治疗方案有立体定向毁损术、脑深电刺激术、胼胝体切开术、双侧内囊前肢切开术和杏仁核切开术、间充质干细胞移植等。本文将伴精神障碍的MR疾病特征、外科治疗手段及疗效进行综述。