Ⅰ型神经纤维瘤病罕见NF1基因突变一例

患儿,女,4岁,因左侧颌面部肿胀、反复头痛1年左朽在我院神经专科就诊。患儿近1年左侧颌面部肿胀,且肿胀不断加重,伴有反复头痛,可忍,无明显呕吐。患儿为独女,G1P1,足月顺产,出生史无异常,精神运动发育无明显迟缓,无惊厥。母孕期体健。家族中无特殊病史。     

Ⅰ型神经纤维瘤病1例

Ⅰ型神经纤维瘤病(NF1)又称Von Recklinghausen病,是一种常见的常染色体显性遗传病.临床特点为多系统、多器官受损,主要特征为皮肤牛奶咖啡斑和多发性皮肤软组织纤维瘤.儿童NF1罕见,且临床表现不典型,易误诊.现报告本院2007年7月收治的NF1患儿1例.     

儿童神经纤维瘤病I型的临床与监测新进展

神经纤维瘤病(neurofibromatosis,NF)是来源于神经嵴的错构瘤紊乱[1].根据受累下颌骨放射学的表现证实了NF来源于中胚层[2],1882年由Von Reckinghamsence首先报道.它是最常见的神经皮肤综合征.     

神经纤维瘤病1型并癫痫发作15例临床特征

目的总结神经纤维瘤病1型(NF1)并癫痫发作的临床特征。方法病例系列研究, 收集2017年1月至2023年7月在首都儿科研究所附属儿童医院就诊的15例NF1并癫痫发作患儿的病例资料, 对其临床特征、治疗情况和预后进行总结分析。结果 15例NF1并癫痫发作患儿中男12例、女3例。15例患儿均有皮肤咖啡牛奶斑, 6例存在神经发育障碍以智力障碍或发育落后为主。首次癫痫发作年龄为2.5(1.2, 5.5)岁, 癫痫发作形式多样, 包括全面强直-阵挛发作8例、局灶运动性发作6例、痉挛发作4例、强直发作1例、失神发作1例、全面性肌阵挛发作1例、局灶性继发双侧强直-阵挛发作1例。14例可获得颅脑磁共振成像结果的患儿中, 6例胼胝体、基底节、丘脑、小脑等部位点片状异常信号, 3例不同程度脑室扩大, 2例灰白质分界模糊, 1例胼胝体发育不全, 余无明显异常。13例符合癫痫诊断的患儿中, 8例应用1～2种抗癫痫药物后不再发作, 1例药物难治性癫痫患儿在接受左侧颞叶切除术后未再发作, 4例曾应用2～9种抗癫痫药物, 仍未控制发作。1例复杂热性惊厥患儿发热时口服地西泮预防性治疗, 未再发作, 1例患儿仅非诱发...     

儿童神经纤维瘤病Ⅰ型的临床与监测新进展

神经纤维瘤病 (ｎｅｕｒｏｆｉｂｒｏｍａｔｏｓｉｓ,ＮＦ)是来源于神经嵴的错构瘤紊乱[1] 。根据受累下颌骨放射学的表现证实了ＮＦ来源于中胚层[2 ] ,1882年由ＶｏｎＲｅｃｋｉｎｇｈａｍｓｅｎｃｅ首先报道。它是最常见的神经皮肤综合征。该病主要表现为咖啡牛奶斑 ,皮肤神经纤维瘤 ,虹膜Ｌｉｓｃｈ小体。本病临床表现多种多样 ,除累及中枢及周围神经系统外 ,还有多系统受累[1] 。一、分类　Ｒｉｃｃａｒｄｉ提出ＮＦ包括 7个独特形式的分类 :1.ＮＦ Ⅰ (周围型 ) :最常见 ,占 80 %～ 90 % ;2 .ＮＦ Ⅱ (双侧听神经或中枢性ＮＦ) :主要表…     

1型神经纤维瘤病发病机制的研究进展

1型神经纤维瘤病(neurofibromatosis type 1, NF1)是常见的常染色体显性遗传病之一。该疾病由NF1基因突变所引起, 可累及多个系统, 具有多种临床表现, 包括牛奶咖啡斑、虹膜结节、神经胶质瘤、孤独症谱系障碍、学习困难、神经纤维瘤和骨骼发育不良等。既往在NF1发病机制的研究中, 多聚焦在神经纤维蛋白调控RAS信号通路。近年来, 研究者开始探索除RAS信号之外的通路, 挖掘神经纤维蛋白潜在功能。该文就近年来对NF1发病机制的研究进展进行综述, 旨在为治疗提供新思路。     

神经纤维瘤病Ⅰ型合并儿童恶性实体肿瘤的临床分析

目的 总结神经纤维瘤病Ⅰ型(NF1)合并恶性实体肿瘤患儿的临床特征及预后。方法 回顾性分析2018年—2022年在我院肿瘤内科诊断并治疗随访的NF1合并恶性实体肿瘤患儿的临床资料,并分析预后。结果 共8名患儿纳入分析,男女各4例。诊断NF1的中位年龄为6.8(0.9-12.9)岁,诊断恶性实体肿瘤的中位年龄为5.3(0.9-13.3)岁。6例在实体肿瘤诊断时或之后确诊为NF1,仅2例在肿瘤诊断前确诊。肿瘤包括3例恶性周围神经鞘瘤、2例横纹肌肉瘤、2例视神路胶质瘤和1例神经母细胞瘤。所有患儿接受化疗;7例进行手术治疗,其中6例完全切除;4例接受放疗。随访中位时间为12.5(1-68)个月,7例存活,复发3例。结论 NF1可合并多种恶性实体肿瘤,早期识别NF1合并恶性肿瘤。     

神经纤维瘤病1家系报告

患儿,男,5岁,因“昏迷、发热、呕吐3 d”入院。1岁内反复无热惊厥3次,可自行缓解,当地按“低钙惊厥”治疗“好转”;近1年来反复在玩耍中突然摔倒,立即或数小时后开始昏迷,期间伴中度发热、频繁呕吐,当地诊所治疗(具体不详),2~3 d后可恢复正常。3 d前再次出现类似病症而来我院就     

儿童Ⅰ型神经纤维瘤病伴巨大颅骨缺损一例

患儿：女，3岁。因发现右颞部颅骨缺损逐渐增大2年余入院。患儿系孕38周剖腹产。生后无窒息，出生时即发现右侧颞骨有一小缺损，约1cm×2cm，当时未在意。患儿5个月大小时颅骨缺损增大而行头颅CT检查示右侧颞骨缺损，约2cm×3cm，未见占位性病变，故未予治疗，此后颞骨缺损仍继续增大，为进一步治疗来我院检查。患儿生长发育与同年龄儿童相仿。前囟已闭，右颞部缺损约6cm×7cm大小，     

A novel mutation in the NF1 gene in two siblings with neurofibromatosis type 1 and bilateral optic pathway glioma

We present the clinical and ophthalmological findings, genetic analysis, and therapy of two siblings with NF1 and bilateral OPG. In genetic analysis, a heteroduplex profile was detected in exon 4b of the NF1 gene for the affected patients and mother. Sequencing of the DNA samples identified a C > T nucleotide change in exon 4b (c484CAG > TAG). This nonsense mutation resulted in a change of glutamine to a stop codon (Q162X) and is a novel NF1 gene alteration.     

NO ABERRANT METHYLATION OF NEUROFIBROMATOSIS 1 GENE (NF1) PROMOTER IN PILOCYTIC ASTROCYTOMA IN CHILDHOOD

Tumours of the central nervous system are the most frequent solid tumours in childhood. With 30 % - 40 % of this heterogenous group, low-grade astrocytomas represent the most common subtype. Neurofibromatosis type 1 (NF1) is strongly associated with the development of pilocytic astrocytoma (PA), frequently appearing as optic glioma. Neurofibromatosis 1 gene (NF1) fulfills the criteria of a tumour suppressor gene and is deleted or mutated heterozygously in patients with NF1. This suggests an involvement in the development of PA. To clarify whether silencing of NF1 by promoter methylation plays a role in PA and especially in optic glioma, we investigated the methylation status in 30 PA, 6 of which had optic glioma. However, we found no methylation at the NF1 promoter region in PA. To rule out that silencing of NF1 by promoter methylation is restricted to higher-grade astrocytomas, we analyzed 15 pediatric WHO II° and IV° astrocytomas. 12 astrocytomas II° and 3 glioblastomas displayed no NF1 promoter methylation. We conclude that NF1 silencing by methylation plays no role in low-grade astrocytoma.     

NO ABERRANT METHYLATION OF NEUROFIBROMATOSIS 1 GENE (NF1) PROMOTER IN PILOCYTIC ASTROCYTOMA IN CHILDHOOD

Tumours of the central nervous system are the most frequent solid tumours in childhood. With 30 % - 40 % of this heterogenous group, low-grade astrocytomas represent the most common subtype. Neurofibromatosis type 1 (NF1) is strongly associated with the development of pilocytic astrocytoma (PA), frequently appearing as optic glioma. Neurofibromatosis 1 gene (NF1) fulfills the criteria of a tumour suppressor gene and is deleted or mutated heterozygously in patients with NF1. This suggests an involvement in the development of PA. To clarify whether silencing of NF1 by promoter methylation plays a role in PA and especially in optic glioma, we investigated the methylation status in 30 PA, 6 of which had optic glioma. However, we found no methylation at the NF1 promoter region in PA. To rule out that silencing of NF1 by promoter methylation is restricted to higher-grade astrocytomas, we analyzed 15 pediatric WHO II° and IV° astrocytomas. 12 astrocytomas II° and 3 glioblastomas displayed no NF1 promoter methylation. We conclude that NF1 silencing by methylation plays no role in low-grade astrocytoma.     

Complex epileptic (Foix–Chavany–Marie like) syndrome in a child with neurofibromatosis type 1 (NF1) and bilateral (opercular and paracentral) polymicrogyria

The association of brain malformations and symptomatic epilepsy in the setting of neurofibromatosis type 1 (NF1) is rarely reported. When it occurs, patients can present clinically with infantile spasms, focal seizures, generalized tonic clonic seizures or atypical absences. We report on a 10-year-old (molecularly proven) NF1 girl manifesting a complex epileptic syndrome resembling the Foix–Chavany–Marie spectrum (also known as opercular syndrome) associated with bilateral (opercular and paracentral lobular) polymicrogyria (PMG). Anecdotal cases of unilateral PMG in the setting of NF1 have been described in association with other-than-opercular epileptic syndromes. The typical clinical opercular syndrome consisting in mild mental retardation, epilepsy and pseudobulbar palsy is usually associated to bilateral perisylvian PMG (BPP)
Conclusion: To the best of our knowledge, the complex epileptic syndrome hereby reported has not been previously recorded in the setting of NF1. In addition, the present girl manifested all the clinical features of an opercular syndrome but had an asymmetrical PMG (not a BPP).     

进行性家族性肝内胆汁淤积症1型1例临床特点和ATP8B1基因突变分析

进行性家族性肝内胆汁淤积症1型 （PFIC1） 是一种ATP8B1基因突变导致的以进行性胆汁淤积为主要临床表现的常染色体隐性遗传病。该文报道1例经ATP8B1突变分析证实的PFIC1患儿临床和遗传学特征。患儿为1岁2个月的男孩,因发现皮肤黄染10月余就诊。发病后先后在多家医院诊治,病因不详,疗效不佳。体查发现皮肤巩膜黄染,肝右肋下4cm,剑突下2cm,脾左肋下2cm可触及。肝功能检查发现血清胆汁酸、胆红素、转氨酶等均升高,而γ-谷氨酰转肽酶水平未见异常。诊断为遗传性胆汁淤积症,但病因不明。1岁8个月时经胆囊结肠Roux-en-Y吻合术,之后患儿黄疸迅速消退。5岁1个月时经全基因组测序及Sanger测序验证,发现患儿为ATP8B1基因突变c.2081T > A （p.I694N） 的纯合子,最终确诊为PFIC1。电话随访至6岁,黄疸未再反复,但远期预后有待观察。     

甲基丙二酸尿症cblB型1例及其MMAB基因新突变

cblB缺陷是甲基丙二酸尿症中的罕见类型,该文首次报道1例中国cblB型甲基丙二酸尿症患儿,就其临床经过、血液酯酰肉碱谱、尿液有机酸分析、基因缺陷进行研究.该患儿以代谢性脑病形式起病,液相串联质谱分析显示患儿血液丙酰肉碱显著增高(22.43 μmol/L,参考值 1.0~5.0 μmol/L),丙酰肉碱/乙酰肉碱比值轻度增高(0.51,参考值0.03~0.50),尿液甲基丙二酸(195.41 mmol/mol肌酐,正常值0.2~3.6 mmol/mol肌酐)及其代谢产物浓度增高,血清总同型半胱氨酸浓度正常,符合单纯型甲基丙二酸血症.患儿MUT基因分析未见突变,MMAB基因存在c.562G>A(p.V188M)和c.577G>A(p.E193K)杂合突变,确诊为cblB型甲基丙二酸尿症.其中,c.562G>A为新突变.经羟钴铵肌肉注射、口服左卡尼汀、低蛋白饮食及特殊配方奶粉治疗后,患儿病情逐渐好转.随访至患儿3岁11个月,智力运动明显进步.cblB缺陷患者缺乏特异性症状,临床表型为单纯型甲基丙二酸尿症,可通过代谢筛查及MMAB基因分析获得确诊.     

Neuropsychological profile in Italian children with neurofibromatosis type 1 (NF1) and their relationships with neuroradiological data: Preliminary results

Background

Neurofibromatosis type 1 is a genetic disorder associated with cognitive deficits, learning disabilities and behavioral problems. These domains appear to have a still controversial debated association with local areas of T2-hyperintensities on MRI images, called unidentified bright objects (UBOs).

Dravet�ۺ����ٴ���SCN1A����ͻ���������60�����棩

??Objective??To study the clinical features and SCN1A genes detection results in children with Dravet syndrome in order to provide reference for clinical treatment. Methods??The clinical data??SCN1A genes reports and antiepileptic drug effects of 60 DS children who were diagnosed from December 2013 to December 2015 were collected from the Children’s Hospital of Fudan University. Results??The onset of seizures occured during 1-9 months with a median of 6 months and 83.3% of patients were febrile seizures at frist onset??they were heat sensitive??and hot water bath induced seizures in 63.3%??38/60??. There were multiple phenotypes??including generalized tonic-clonic seizures??95.0%??57/60????partial seizures??alternating unilateral seizure????78.3%??47/60????status epilepticus??65.0%,39/60????myoclonic seizures??65.0%??39/60????and atypical absence ??63.3%??38/60??. Seizure ouccurred most frequently??2-3 times per month?? in 1-3 years of age. The median age of mental retardation was 18 months. The number of mental retardation and the positive rate of EEG increased with age. Dravet syndrome were intractable. In patients who used sodium ion blocking drugs 40.0%??24/60?? children had aggravated seizures. 80.0%??48/60?? patients had SCN1A mutation with missense and nonsense mutation accounting for over a half. There was no correlation between SCN1A mutations and onset age??sex??seizure type or seizure frequency. Conclusion??Dravet syndrome is a childhood-onset epileptic encephalopathy??which is not rare in the national seizure center. The positive rate of SCNIA mutation is high??which can help the diagnosis of DS. Anti-epiletic drug treatment for DS is difficult and the misuse of drugs is in a high proportion??so the diagnosis and treatment level still needs to be improved.