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.

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.

Objective:To summarize and analyze the clinical and genotype features of female-restricted X-linked syndromic mental retardation-99(MRXS99F, OMIM: 300968)caused by USP9 X gene mutation, and to improve the clinicians′ understanding of the disease. Methods:Clinical data and genotypes of 2 children with MRXS99F treated in the Children′s Hospital of Nanjing Medical University in March 2020 (case 1) and June 2020 (case 2) were analyzed, and the relevant databases at home and abroad were reviewed to summarize the clinical characteristics and gene variation characteristics of the disease.Results:The 2 cases were 6 months old (case 1) and 5 years old (case 2), both showed psychomotor retardation.Case 1 presented a short stature, pigment abnormality, characteristic facial features, hypotonia, recurrent respiratory tract infections, laryngeal cartilage hypoplasia, atrial septal defect, feeding difficulty, hearing loss and brain hypoplasia.Case 2 had abnormal electroencephalogram.As confirmed by whole-exome sequencing, two children carried c. 6972+ 1G>A, c.6437C>T of USP9 X, respectively.Neither of the 2 variations was previously reported.Twenty-two cases of MRXS99F caused by USP9 X gene mutation were reported in 4 literatures globally, and 24 cases were combined with this study.The clinical manifestations of 20/22 children had special faces.All of them accompanied mental retardation combined with motor and language retardation, and carried neonatal variation. Conclusions:This is the first case report of MRXS99F induced by USP9 X gene variation in China.MRXS99F caused by functional deletion and variation of USP9 X gene is mainly characterized by psychomotor retardation, language disorder, special face and multiple congenital malformations.For children with unexplained growth retardation, special face and multiple congenital malformations, genetic testing like high-throughput sequencing should be carried out as early as possible to determine the etiology.

Background Interstitial deletions of chromosome band 10q11-q22 was a genomic disorder distinguished by developmental delay, congenital cleft palate and muscular hypotonia. The phenotypes involved were heterogeneous, hinge on the variable breakpoints and size. Case presentation Here, we presented a patient with soft palate cleft, growth and development delay. The patient was a 2 years and 5 months girl who was not able to walk unless using a children’s crutches to support herself. Whole-exome sequencing (WES) and whole-genome mate-pair sequencing (WGMS) were both performed by next generation sequencing (NGS). A 20.76 Mb deletion at 10q11.23q22.1 (seq[GRCh37/hg19]del(10)(50,319,387-71,083,899) × 1) was revealed by the WGMS, which was verified as de novo by quantitative polymerase chain reaction (QPCR). Conclusion Children with 10q11-q22 deletions greater than 20 MB have never been reported before, and we are the first to report and provide a detailed clinical phenotype, which brings further knowledge of 10q11-q22 deletions.

Objective:To detect the mutations of the ALDH3A2 gene in 2 families of patients with Sj?gren-Larsson syndrome(SLS), and to guide their parents to be pregnant rationally. Methods:Two SLS children admitted to Children′s Hospital of Nanjing Medical University were clinically researched and analyzed of their ALDH3A2 gene mutations, comprehensive rehabilitation treatment, and systematic review.The clinical studies of 16 children and 8 cases of ALDH3A2 gene mutation sites that have been reported in China so far were analyzed in order to provide theoretical basis for early diagnosis, treatment, genetic counseling, and prenatal diagnosis. Results:The 2 children in this study had typical ichthyosis-like skin changes, spastic diplegia or quadriplegia, and cannot walk independently, combined with mental retardation and delayed language development.The patients′s ALDH3A2 gene changed, and both their parents and unaffected sister were heterozygous carriers of the mutation. Conclusions:The detection of the ALDH3A2 gene in suspicious SLS patients works well in early diagnosis, rehabilitation treatment, and can improve curative effect.At the same time it is more meaningful to guide genetic counseling and prenatal diagnosis.

Objective To investigate any protective effect of transplanting EPhrinB2-modified bone marrow mesenchymal stem cells ( BMSCs) with a rat model of cerebral palsy. Methods BMSCs were isolated and cultured, then further modified by lentivirus-mediated transfection of the EPhrinB2 gene. Ninety-six Sprague-Dawley rats were randomly divided into a sham group, a solvent control group ( PBS group) , an empty lentivirus group ( EGFP group) and an EPhrinB2 recombinant lentivirus group ( EPhrinB2 group) , each of 24. A model of cerebral palsy was estab-lished in the rats of the PBS, EGFP and EPhrinB2 groups using hypoxic-ischemic encephalopathy. Seven days after the operation, the lateral ventricles of the PBS, EGFP and EPhrinB2 group mice were injected with phosphate-buff-ered saline solution, BMSCs or EPhrinB2-modified BMSCs respectively. EPhrinB2 protein expression in the hippo-campus was detected using immunohistochemistry 28 days after the operation. The neuron density in the CA1 region of the hippocampus was observed using hematoxylin and eosin staining, and any apoptosis of hippocampal neurons was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling. The expression of nestin and CD31 in the hippocampus was observed using immunofluorescence assays. Morris water maze testing was also conducted to e-valuate changes in learning and memory ability. Results Compared with the other 3 groups, a significant increase in the expression of protein EPhrinB2 was observed in the hippocampuses of the EPhrinB2 group rats. The pathologi-cal changes in the hippocampus among the EPhrinB2 group were significantly less severe than those in the PBS and EGFP groups. The rate of apoptosis in the hippocampuses of the EPhrinB2 group was significantly lower than that of the other groups. Immunofluorescence showed that nestin- and CD31-positive cells were significantly more numerous in the EPhrinB2 group than in the others. In the water maze the average latency of the EPhrinB2 group was signifi-cantly shorter than those of the other groups. Conclusion Lentiviral-mediated EPhrinb2 transfection of BMSCs into the hippocampus can promote EPhrinB2 gene expression, promote angiogenesis and neuron differentiation, inhibit ap-optosis and accelerate the repair of injured nerves.

Sj(o)gren-Larsson综合征(SLS)是一种罕见的常染色体隐性遗传性神经皮肤综合征,临床表现主要包括先天性鱼鳞病、精神发育落后、双侧或四肢痉挛性瘫痪三联征.我国迄今报道10余例,其中相关基因报道较少,现对南京医科大学附属儿童医院康复科收治的1例SLS患儿家系进行ALDH3A2基因突变研究,探讨此病临床表现与基因的关系.

目的 分析新生儿鸟氨酸氨甲酰转移酶缺乏症(OTCD)的临床特征及鸟氨酸氨甲酰转移酶(OTC)基因突变位点。 方法 分析1例疑诊新生儿OTCD患儿的临床特征，采用高通量测序技术筛选遗传代谢疾病相关基因，应用聚合酶链反应和Sanger测序的方法对患儿及其父母血样进行OTC基因突变检测。中国知网和万方数据库上检索文献，比较分析国内已报道新生儿OTCD患儿的临床特征及OTC基因突变位点。 结果 本例患儿男性，日龄6 d，因气促6 d，反应差、发热伴抽搐1 d入院，质谱分析显示血氨>500 μmol/L，乳酸5.7 mmol/L。基因检测发现患儿OTC基因第2外显子发生c.176T>G (p.Leu59Pro)错义突变，是一新发现的OTC基因突变位点。文献报道国内有18例新生儿OTCD患儿，全为男性，临床上多数表现为反应差、吃奶差或呕吐、呼吸困难、抽搐、嗜睡或昏迷等症状，质谱结果显示患儿血氨均明显升高，仅7例患儿行OTC基因突变分析。 结论 本研究丰富了新生OTCD患儿的临床表现和基因突变类型，高通量测序技术可用于疑诊OTCD患儿的基因检测，OTC基因c.176T>G是一新发生的错义突变，国内外未见报道。

Objective To explore the clinical features and the gene mutations in MECP 2 duplication syndrome. Methods The clinical data of a child with developmental retardation and hypophrenia accompanied with respiratory tract infection was analyzed retrospectively. Microarray analysis technique was used to detect the genes in the patient and his family. The pertinent literature was reviewed. Results A 1-year and 7-month old boy was found to have hypotonia, developmental delay, and recurrent respiratory tract infections after birth. Microarray analysis showed a duplication of 441.88kb in Xq28 area and diagnosis of MECP2 duplication syndrome was confirmed. His grandmother, mother, and two aunts were found duplication of 441.73-441.88kb in Xq28 area, all of whom were MECP2’s female carrier. Conclusions The improvement of chromosome chip technology inspection is helpful to the early diagnosis of MECP2 duplication syndrome.

目的：观察丙戊酸钠对痉挛型脑性瘫痪（简称脑瘫）伴发临床下癫痫样放电（ SEDs ）患儿临床发作及癫痫样放电次数的影响。方法将76例伴发SEDs的痉挛型脑瘫患儿按照完全随机数字表法分为观察组和对照组各38例，两组均给予常规综合康复治疗和抗癫痫治疗，观察组在此基础上口服丙戊酸钠，疗程1年。观察两组治疗期间癫痫临床发作情况，无临床发作患儿于疗程结束行16导脑电图检查，记录癫痫样放电次数以评价疗效。结果观察组治疗期间有癫痫临床发作2例、无临床发作36例，对照组分别为4、34例；两组比较，P＞0．05。脑电图检查结果显示，观察组对放电次数控制有效13例（34．2％）、无效23例，对照组分别为4（10．5％）、30例；两组有效率比较，P＜0．05。结论丙戊酸钠对伴发SEDs的痉挛型脑瘫患儿转化为癫痫临床发作无明显影响，但可以明显减少无临床发作患儿的SEDs次数。

OBJECTIVE To analyze the clinical data of the children with asthma induced by Mycoplasma pneumoni‐ae infection and explore the treatment measures so as to provide guidance for the improvement of efficacy . METHODS From Mar 2012 to Mar 2013 ,a total of 80 children with conformed asthma were recruited as the study objects and were divided into the observation group with 40 cases (the children with M .pneumoniae infection‐in‐duced asthma) and the control group with 40 cases (the children with non‐M .pneumoniae infection‐induced asth‐ma);the clinical symptoms of the two groups of children were observed and recorded .RESULTS Of the 40 children in the observation group ,33 (82 .5% ) cases were with fever ,among whom the children with the body temperature more than 37 .3 ℃ accounted for 42 .5% (17 cases) ,the children with the body temperature more than 38 ℃35 .0% (14 cases) ,the children with the body temperature more than 39 ℃ 5 .0% (2 cases) .Of the 40 children in the control group ,18 (45 .0% ) cases were with fever ,among whom the children with body temperature more than 37 .3 ℃ accounted for 35 .0% (14 cases) ,the children with the body temperature more than 38℃ 10 .0% (4 ca‐ses) .The clinical manifestations such as the wheezing ,fever ,and pulmonary infections varied between the obser‐vation group and the control group .CONCLUSION The clinical symptoms of the observation group are more severe than those of the control group .For the treatment of the children with M .pneumoniae infection‐induced asthma , it is necessary to use macrolides and bronchodilators in combination with corticosteroids sugar inhalation ,with the daily care supplemented .

Objective To assess the role and value of acupuncture therapy in rehabilitation of children with spastic cerebral palsy by using the Gross Motor Function Measure (GMFM 88) and visual evoked potential (VEP). Methods Sixty children with spastic cerebral palsy aged 1 to 7 included in the study. The acupuncture group (n = 20) received scalp and body acupuncture; the rehabilitation training group (n = 20) received physical therapy with the Bobath method; and acupuncture and rehabilitation training group (n = 20) received combination therapy. Results The total effectiveness rate was significantly higher in both acupuncture group and acupuncture and rehabilitation training group than in rehabilitation training group. GMFM was higher in both acupuncture group and acupuncture and rehabilitation training group than in rehabilitation training group. Improvement rate of VEP was significantly greater in both acupuncture group and acupuncture and rehabilitation training group than in rehabilitation group (P < 0.05 and P < 0.01). Conclusions Acupuncture can significantly improve brain cell metabolism in children with spastic cerebral palsy , partially even fully compensate brain function, and promote brain tissue repair and functional plasticity.

OBJECTIVE To investigate the influence of scalp acupuncture treatment on cognitive dysfunction and brainstem auditory evoked potential on children with cerebral palsy.METHODS 40 cerebral palsy patients with cognitive dysfunction were recruited and randomly divided into treatment group (20 cases using scalp acupuncture treatment and comprehensive rehabilitation training)and control group(20 cases only using comprehensive rehabilitation training).After a course of therapy,Gesell developmental scales and brainstem auditory evoked potential of both groups were statistically analyzed.RESULTS Gesell developmental scales was in a statistically significant difference compared with before in both groups(P<0.01,P<0.05).The wave PL,IPL andⅤwave response threshold were improved significantly.There was significant difference between two groups after treatment(P<0.05).CONCLUSION Scalp acupuncture treatment is more effective than rehabilitation training alone in improving cognitive dysfunction of cerebral palsy,and it can effectively improve the abnormal BAEP.

Objective To observe the therapeutic effects of hyperbaric oxygen (HBO) at different time points in infants with cerebral palsy.Methods Sixty cases of cerebral palsy with an age of 3 months were randomly divided into 4 groups:group 1,2,3,4,each consisting of 15 cases.All the infants of the 4 groups were given routine rehabilitation treatment until they were 1 year old.The sick infants in group 1,2 and 3started HBO therapy at the following ages:3 to 4 months old,4 to 6 months old and over 6 months old respectively,with a treatment course of 8 weeks and a total of 40 sessions.The infants in groups 4 were not treated with HBO.Gross motor function was evaluated with Gross Motor Function Measure (GMFM).Intelligence was evaluated with Gesell Development Scale.Then,developmental quotient and total developmental quotient in gross motor,fine motor,adaptation,language and individual-social domains were calculated.Results At one year old,GMFM,developmental quotients in the above five domains and total developmental quotients of all the sick infants in the 4 groups improved significantly,when compared with those before treatment.Of all the patients in the 4 groups,the patients in groups 1 improved more significantly than those in group 2,3 and 4,with statistical significance (P ＜ 0.05).The patients in groups B improved more significantly than those in group 3 and 4,also with statistical significance (P ＜ 0.05).No statistical significance could be noted in therapeutic effects,when a comparison was made between group 3 and 4 (P ＞0.05).No serious adverse reactions could be noticed in the patients of the 4 groups during treatment.Conclusions Therapeutic time points of HBO therapy played an important role in the treatment of cerebral palsy in infants.The earlier the HBO therapy was implemented,the better the treatment.Optimal therapeutic effects could be achieved,if HBO therapy was started within 3 to 4 months after onset of the disease.Less optimal therapeutic results could be achieved,if HBO intervention was given within 4 to 6 months.And there would be no significant effects,if HBO therapy was started 6 months after the onset of disease.

目的 观察远近配穴针刺治疗脑瘫流涎患儿的疗效.方法 采用随机数字表法将60例脑瘫流涎患儿分为治疗组及对照组,2组患儿均给予言语康复训练,治疗组在此基础上加用远近配穴针刺疗法.于治疗前及治疗3个月后对2组患儿流涎改善情况进行评定.结果 治疗组患儿10 min唾液量及流涎程度、频度均较治疗前及对照组明显改善(P＜0.05);对照组治疗后10 min唾液量未见明显降低(P＞0.05),但流涎频度及程度均较治疗前明显改善(P＜0.05).结论 在常规言语康复训练治疗脑瘫流涎患儿基础上辅以远近配穴针刺治疗,能进一步改善脑瘫患儿流涎症状,提高康复疗效。

Objective To observe the therapeutic effect of transcutaneous electric nerve stimulation on children with flaccid cerebral palsy.Methods 40 children with flaccid cerebral palsy were divided into 2 groups: treatment group(n=20) and control group(n=20).2 groups were given conventional rehabilitation training for 30 d,while the treatment group added transcutaneous electric nerve stimulation on quadriceps femoris for 30 d.Quadriceps femoris was assessed by Modified Lovett classification,gross motor function was assessed by Gross Motor Function Measure(GMFM),and integrated electromyogram(iEMG) and root mean square(RMS) were recorded.Results There was significant improvement in 2 groups in Modified Lovett classification,GMFM,and iEMG and RMS(P<0.05) while the treatment group was better than the control group(P<0.05).Conclusion Transcutaneous electric nerve stimulation can enhance the muscle tone and strength of quadriceps femoris to improve gross motor function for children with flaccid cerebral palsy.

OBJECTIVE: To observe the clinical efficacy of Xiao’er zhili syrup in the treatment of language disorder of cerebral palsy children. METHODS: 60 cerebral palsy (CP) children were randomly divided into normal treatment group (30 cases) and Xiao’er zhili syrup group (30 cases). Normal treatment group was given comprehensive rehabilitation therapy which was mainly based on physical therapy, occupational therapy, massage, physiotherapy and scalp-acupuncture. Xiao’er zhili syrup group was additionally given Xiao’er zhili syrup (10 mL, tid) on the basis of comprehensive rehabilitation therapy. A treatment course lasted for 1 month. The examination of CRRC (S-S) and intelligence evaluation of Gesell method were conducted at the beginning and end of treatment. RESULTS: In Xiao’er zhili syrup group, the ability of language rehabilitation were better than routine treatment group, there was statistical significance (P0.05). Gesell score of Xiao’er zhili syrup group was superior to that of routine treatment group, there was statistical significance (P0.01). CONCLUSION: Xiao’er zhili syrup has obvious effects on language disorder in cerebral palsy children and has low ADR.

婴儿高压氧舱治疗为小儿脑损伤的康复开辟了新的途径,高压氧能明显提高脑组织的血氧含量,促进损伤的脑组织修复,改善脑循环,减轻脑水肿,阻断神经元凋亡,促进缺血半暗带恢复,对神经细胞再生、神经功能恢复起到药物无法替代的作用[1].

Objective To investigate the effect of muscle spasticity therapeutic apparatus on spastic cerebral palsy(CP) in children.Methods Twenty-two spastic CP children aged from 2 to 4 years old were randomly divided into treatment group and control group with 11 cases in each group.All children were treated with physical therapy,massage and cerebral circulation therapy,while those of treatment group were added with muscle spasticity therapeutic apparatus.It lasted for 30 days with one time daily,15 minutes each time.All children were evaluated in terms of tests of the muscle tone of the lower limb by Modified Ashworth Scale(MAS),passive range of motion(PROM) of the popliteal angle,D and E dimensions of gross motor function measure score-88(GMFM-88),and the composite spasticity scale(CSS) at the start and after 30 days.Results No statistically significant differences were found in clinical assessments(the popliteal angle,CSS,GMFM-88)before treatment between 2 groups(Pa0.05).MAS and CSS of the lower extremity muscle tone of all children in 2 groups were decreased 30 days after treatment(Pa0.05).There were significant improvements of the popliteal angle,section D,E of the GMFM-88 for variation in treating period(Pa0.05).Conclusions Muscle spasticity therapeutic apparatus decreases the muscle tone of the children and improves gross motor function and range of motion in spastic CP,so it can be an effective therapeutic technique in children with spastic CP.