ObjectiveThis study aims to describe the characteristics of the brain network attributes in children diagnosed with Infantile Epileptic Spasms Syndrome (IESS) and to determine the influence exerted by adrenocorticotrophic hormone (ACTH) or methylprednisolone (MP) on network attributes.MethodsIn this retrospective cohort study, we recruited 19 infants diagnosed with IESS and 10 healthy subjects as the control from the Pediatric Neurology Department at the Third Affiliated Hospital of Zhengzhou University between October 2019 and December 2020. The first thirty-minute processed electroencephalograms (EEGs) were clipped and filtered into EEG frequency bands (2 s each). A comparative assessment was conducted between the IESS group and the controls as well as the pre- and post-treatment in the IESS group. Mutual information values for each EEG channel were collected and compared including characteristic path length (CPL), node degree (ND), clustering coefficient (CC), and betweenness centrality (BC), based on graph theory.ResultsComparing the control group, in the IESS group, there was an increase in CPL of the Delta band, and a decrease in ND and CC of the Delta band during the waking period, contrary to those during the sleeping period (P < 0.05), a decreased in CPL of the fast waves and an increase in ND and CC (P < 0.05) in the sleep-wake cycle, and a decrease in ND and CC of the Theta band in the waking phase. Post-treatment compared with the pre-treatment, during the waking ictal phase, there was a noted decrease in CPL in the Delta band and fast waves, while an increase was observed in ND and CC (P < 0.05).ConclusionsThe Delta band and fast waves are crucial components of the network attributes in IESS.SignificanceThis investigation provides a precise characterization of the brain network in children afflicted with IESS, and lays the groundwork for predicting the prognosis using graph theory.

目的 观察癫痫患儿规范应用抗癫痫发作药物(antiseizure medications,ASMs)或联合糖皮质激素治疗后低纤维蛋白原血症发生情况及严重程度,探讨抗癫痫治疗后发生低纤维蛋白原血症的因素和治疗结局.方法 33例应用ASMs或联合糖皮质激素规范治疗后发生低纤维蛋白原血症的癫痫患儿,确诊低纤维蛋白原血症后给予人纤维蛋白原、必要时降低丙戊酸钠药物剂量等治疗.记录癫痫发作类型、综合征类型、病因、治疗后发生低纤维蛋白原血症的中位时间、发生低纤维蛋白原血症时的治疗方案;于抗癫痫治疗前、诊断低纤维蛋白原血症时、低纤维蛋白原血症治疗次日及治疗后1个月检测纤维蛋白原(fibrinogen,Fib)、凝血酶原时间、凝血酶时间、活化部分凝血活酶时间、纤维蛋白降解产物、D-二聚体、中性粒细胞计数、白细胞计数、血红蛋白、血小板计数.随访至2022年8月,观察患儿低纤维蛋白原血症复发情况.结果 33例发作类型为痉挛发作24例,强直-阵挛发作6例,强直痉挛发作2例,肌阵挛发作1例;婴儿癫痫性痉挛综合征21例;病因不明14例,结构性病因13例,遗传性病因6例;1例因不易止血发现且合并轻度肝功能损伤,余32例在随访期间常规检测血常规、凝血功能时发现.诊断低纤维蛋白原血症时,33例中32例应用丙戊酸钠,其中26例(含21例婴儿癫痫性痉挛综合征)应用糖皮质激素联合丙戊酸钠等ASMs,1例应用糖皮质激素联合左乙拉西坦、托吡酯及氯硝西泮,6例未应用糖皮质激素(5例应用丙戊酸钠联合其他ASMs,1例单用丙戊酸钠).诊断低纤维蛋白原血症时Fib水平[0.930(0.850,0.980)g/L]低于抗癫痫治疗前[2.460(2.140,2.675)g/L](Z=-5.013,P＜0.001),凝血酶时间[(20.676±1.756)s]长于抗癫痫治疗前[(18.284±1.605)s](t=7.478,P＜0.001),活化部分凝血活酶时间[(34.803±5.446)s]短于抗癫痫治疗前[(40.447±5.402)s](t=-6.030,P＜0.001).31例诊断低纤维蛋白原血症时Fib水平＜1.0 g/L,静脉滴注人纤维蛋白原,30例应用丙戊酸钠者同时口服左卡尼汀,次日低纤维蛋白原血症纠正;2例诊断低纤维蛋白原血症时Fib水平为1.0 g/L,口服左卡尼汀并降低丙戊酸钠剂量后低纤维蛋白原血症得到纠正.33例低纤维蛋白原血症治疗次日Fib水平[1.950(1.515,2.490)g/L]高于诊断低纤维蛋白原血症时(P＜0.05),凝血酶原时间[(12.564±1.140)s]、凝血酶时间[(17.491±1.515)s]均短于诊断低纤维蛋白原血症时[(13.752±1.591)、(20.676±1.756)s](P＜0.05);低纤维蛋白原血症治疗1个月Fib水平[1.550(1.390,1.659)g/L]高于诊断低纤维蛋白原血症时(P＜0.05),凝血酶时间[(17.680±1.465)s]短于诊断低纤维蛋白原血症时(P＜0.05),活化部分凝血活酶时间[(37.601±5.728)s]长于诊断低纤维蛋白原血症时(P＜0.05).中位随访32.75(24.90,43.88)个月,1例间隔2个月再次发生低纤维蛋白原血症,再次静脉滴注人纤维蛋白原并降低丙戊酸钠剂量后纠正,余患儿未再发生低纤维蛋白原血症.结论 应用丙戊酸钠或联合糖皮质激素治疗、发作类型为婴儿癫痫性痉挛综合征的癫痫患儿易发生低纤维蛋白原血症,临床应注意监测癫痫患儿凝血功能,发现低纤维蛋白原血症后及时处理,减少相关出血并发症.

Objective:To analyze the clinical characteristics and genetic basis of two children patients with CHARGE syndrome.Methods:The clinical features of the two patients were analyzed, and potential variants were detected by Trio whole exome sequencing (trio-WES) of the probands and their parents.Results:Child 1 has manifested cerebellar vermis dysplasia, enlargement of cerebral ventricles, whereas child 2 manifested with infantile spasm and congenital hip dysplasia. Both children were found to harbor de novo heterozygous variants of the CHD7 gene, namely c. 4015C>T (exon 17) and c. 5050G>A (exon 22). Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were rated as pathogenic variants, and the related disease was CHARGE syndrome. Furthermore, child 2 was also found to harbor a novel heterozygous c. 6161A>C (p.Gln2054Pro) missense variant of COL12A1 gene, which was rated as possibly pathogenic, and the associated disease was Bethlem myopathy type 2, which is partially matched with the patient’s clinical phenotype. Conclusion:The special clinical phenotypes shown by the two children harboring novel CHD7 variants have further expanded the phenotypic spectrum of CHARGE syndrome.

Congenital disorder of glycosylation (CDG) is a group of genetic metabolic diseases involving multiple organs. A case of CDG caused by SLC35A2 gene mutation was diagnosed. The clinical characteristics included spasms, developmental retardation and multiple malformations. Video-electroencephalogram showed dysrhythmia. A de novo heterozygous missense mutation of SLC35A2 gene was detected by whole exome sequencing: c.844G>A (p.Gly282Arg). It was predicted to be likely pathogenic according to American College of Medical Genetics and Genomics guidelines which had not been reported in China.

Objective: The study aimed to identify the signatures of brain networks using electroencephalogram (EEG) in patients with infantile spasms (IS). Methods Scalp EEGs of subjects with IS were prospectively collected in the first year of life (n = 8; age range 4–8 months; 3 males, 5 females). Ten minutes of ictal and interictal EEGs were clipped and filtered into different EEG frequency bands. The values of each pair of EEG channels were directly compared between ictal with interictal onsets and the sleep-wake phase to calculate IS brain network attributes: characteristic path length (CPL), node degree (ND), clustering coefficient (CC), and betweenness centrality (BC). Results CPL, ND, and CC of the fast waves decreased while BC increased. CPL and BC of the slow waves decreased, while ND and CC increased during the IS ictal onset (P < 0.05). CPL of the alpha decreased, and BC increased during the waking time (P < 0.05). Conclusion The transmission capability of the fast waves, the local connectivity, and the defense capability of the slow waves during the IS ictal onset were enhanced. The alpha band played the most important role in both the global and local networks during the waking time. These may represent the brain network signatures of IS.

目的 观察清醒期、睡眠期婴儿痉挛症(infantile spasms,IS)患儿痉挛发作期间不同频段脑功能网络属性特征路径长度(characteristic path length,CPL)的变化,探讨激素冲击治疗对IS患儿脑功能网络的作用.方法 IS患儿19例(IS组),均行甲泼尼龙或促肾上腺皮质激素冲击治疗;记录IS组激素冲击治疗前、后清醒期、睡眠期、清醒发作期、睡眠发作期脑电图数据,应用matlab软件分析delta、theta、alpha、beta、gamma频段CPL.选取同期行视频脑电图检查结果正常的儿童10例为对照组,比较2组清醒期、睡眠期脑电图delta、theta、alpha、beta、gamma频段CPL.随访1年,观察IS患儿激素冲击治疗后痉挛发作的控制情况.结果 随访1年,痉挛发作完全控制11例,治疗无效8例.激素冲击治疗前IS组患儿清醒期脑电图delta频段CPL[130.79(121.61,144.74)×10-3]高于对照组[128.50(119.11,140.78)×10-3](Z=-2.645,P=0.008),beta、gamma 频段 CPL[89.72(78.65,65 535.00)×10-3、94.22(83.98,65 535.00)×10-3]均低于对照组[107.87(90.37,65 535.00)×10-3、98.33(88.53,65 535.00)×10-3](Z=-9.236,P＜0.001;Z=-3.282,P=0.001);睡眠期脑电图 delta、beta 频段 CPL[129.17(118.06,140.99)×10-3、82.80(74.14,113.68)×10-3]均低于对照组[131.90(122.48,141.69)×10-3、92.38(76.94,65 535.00)×10-3](Z=-2.688,P=0.007;Z=-5.079,P＜0.001).清醒期IS组患儿激素冲击治疗后脑电图beta、gamma频段CPL[94.37(83.64,65 535.00)×10-3、97.98(88.04,65 535.00)×10-3]均高于激素冲击治疗前(Z=-4.503,P＜0.001;Z=-3.611,P＜0.001);睡眠期IS组患儿激素冲击治疗后脑电图beta频段CPL[89.65(79.43,65 535.00)×10-3]高于激素冲击治疗前(Z=-7.311,P＜0.001).IS患儿激素冲击治疗后清醒发作期脑电图delta、alpha、beta、gamma频段CPL[111.73(106.44,117.92)×10-3、110.75(103.97,130.07)×10-3、81.35(74.07,97.43)×10-3、92.61(79.01,65 535.00)×10-3]均低于冲击治疗前[118.16(110.58,130.23)×10-3、115.19(104.83,162.77)×10-3、90.53(76.98,65 535.00)×10-3、96.17(82.78,65 535.00)×10-3](P＜0.05);睡眠发作期脑电图 delta 频段 CPL[116.50(109.31,128.12)×10-3]高于冲击治疗前[113.66(107.56,121.60)×10-3](Z=-4.412,P＜0.001),theta 频段 CPL[131.56(114.90,177.63)×10-3]低于冲击治疗前[153.11(127.55,65 535.00)×10-3](Z=-6.109,P＜0.001).结论 IS患儿清醒期、睡眠期脑电图beta频段传输效率增强,激素冲击治疗可降低发作间期beta频段、睡眠发作期delta频段的传输效率,增强清醒发作期delta、alpha、beta、gamma频段的传输效率,改善脑电图高峰失律、减少高频振荡募集可能.

目的探讨Cornelia de Lange综合征（CdLS）的临床表型及基因型特点。方法回顾分析1例确诊CdLS患儿的临床资料,并总结分析国内已报道病例的情况。结果女性患儿,1岁2月龄,有特殊外貌,智力及运动发育落后,合并四肢畸形及听力异常。基因检测发现患儿HDAC8基因c.675C＞A（p.Y225X）存在新发杂合无义变异,根据ACMG指南预测为致病性变异,确诊CdLS。通过对万方、维普、中国知网及PubMed数据库搜索,发现国内报道CdLS病例46例。其中26例行基因检查,20例（76.9%）存在NIPBL基因变异,3例（11.5%）HDAC8基因变异,1例（3.8%）SCM1A基因变异,2例未发现与临床吻合的致病性基因变异,表型各异。结论 CdLS患儿存在特殊外貌、生长发育迟缓、多器官受累、听力障碍,多数可通过典型临床表型诊断,基因检测有助于非典型患者的早期诊断。

Mental retardation-40 (MRD40) is a rare autosomal dominant neurodevelopmental disorder with a poor prognosis that is caused by a heterozygous mutation in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). It was previously considered a non-syndromic disease due to the lack of specific external features. Only limited international reports describing CHAMP1 mutations are currently available. The present case study was the first to report on a Chinese patient with MRD40. The patient presented with severe global development delay with significant craniofacial dysmorphia. Using trio whole-exome sequencing, a novel de novo frameshift mutation in CHAMP1, NM_032436.2: c.530delCinsTTT, was identified, which expands the spectrum of the known pathogenic variants. The present case report helps to improve the syndromic profile of the rare MRD40 disorder and provides an example for the clinical diagnosis of MRD40.

目的:明确1例Okur-Chung神经发育综合征(Okur-Chung neurodevelopmental syndrome, OCNDS)患者的发病原因。方法:对1例生长发育迟缓、智力障碍、特殊面容、多器官受累的患儿行全外显子组测序，对致病基因变异进行生物信息学分析。结果:患儿存在全面性发育迟缓、特殊面容，合并脐疝和腹股沟疝，全外显子测序显示其 CSNK2A1基因第4外显子c.140G>A杂合错义变异，该变异为新发变异，ClinVar数据库和HGMD数据库均已收录。根据ACMG指南判定为致病性变异，符合OCNDS的诊断。分析其氨基酸保守性，并利用Swiss PDB view软件进行蛋白结构建模分析，发现该变异可导致编码蛋白空间结构改变，从而影响蛋白功能。 结论:携带 CSNK2A1基因第4外显子c.140G>A(p.Arg47Gln)变异的患儿具有高度相似的临床表型，基因检测有助于该病早期诊断。