NR2F1基因变异导致视神经萎缩综合征1例报道并文献复习

目的 回顾性分析NR2F1基因变异导致视神经萎缩综合征的基因变异特点、临床表型、诊断及预后。方法收集1例青岛大学附属医院确诊的Bosch-Boonstra-Schaaf视神经萎缩综合征（BBSOAS）患儿的临床资料并进行相关文献复习。结果 患儿,女,7月17 d,表现为不会抓物,无追视,对检查者缺乏视觉互动行为,面部表情单一,不能独坐。眼底检查示：双侧视盘小而苍白。全外显子测序示：患儿NR2F1基因c.327C>G(p.F109L)错义变异,新发。检索NR2F1数据库共收录89名患者,123个变异,涉及83个核苷酸位点,变异类型最多为错义变异。BBSOAS的临床表型以眼部受累、脑功能受损和脑形态学异常最为显著,比例较高的还有肌张力低下,癫痫及喂养困难。结论 NR2F1基因的新发错义变异c.327C>G(p.F109L)是本例BBSOAS的遗传学病因,导致其严重发育迟缓和视力障碍。     

Kenny-Caffey综合征2型一例并文献复习

目的 探讨Kenny-Caffey综合征2型(KCS2)的临床特征、基因突变特点及诊疗进展.方法 回顾性分析广西医科大学第二附属医院儿科收治的1例KCS2患儿的临床资料.以Kenny-Caffey SyndromeFAM111A geneHypoparathyroidismHypocalcemiaSh...     

儿童原发性1型高草酸尿症1例并文献复习

目的总结儿童原发性1型高草酸尿症（PH1）临床资料,提高对该病的认识。方法采集1例PH1患儿的临床特点、影像学表现,。肾结石分析信息;进行家系调查;对该家系相关成员进行AGXT基因外显子及附近调控区域直接测序,分析突变位点;文献综述。结果女童,3岁时起病,首发症状为肉眼血尿,继腰、背部疼痛,体外震波碎石、排石治疗后结石复发,7年内进展为终末期肾病。腹部B超、X线平片和CT均提示多发双肾脏和输尿管结石。。肾结石成份为单水草酸钙。未发现患儿家族有相同疾病的患者。AGXT基因分析发现,患儿存在c．242C〉A（P．Ser81X）和c．823_824dupAG（P·Ser275delinsArgAlafs）杂合突变,其父亲携带c．823_824dupAG杂合突变,其母亲携带c．242C〉A杂合突变。患儿为AGXT基因复合杂合突变,其中c．242C〉A无义突变为首次报道。结论PH1为罕见遗传性疾病。经影像学证实为多发和复发性双肾结石,排除其他原因所致,应该考虑原发性高草酸尿症,肾结石成份和AGXT基因分析是PH1诊断的重要手段,尤其AGXT基因分析在某些情况下可以替代肝穿刺成为PH1确诊的无创检查;PH1早期诊断和干预将会延缓肾功能恶化,改善预后。     

Crouzon综合征1例报告

目的 分析1例FGFR2基因突变导致Crouzon综合征患儿的病例资料,了解该病的典型特征及分子生物学特点,为临床诊治提供依据。方法 回顾分析Crouzon综合征患儿的临床资料,完善相关辅助检查,同时采集患者及其父母的外周血,应用高通量测序目标序列捕获技术进行家系全外显子组测序,并进行遗传学分析。结果 该患儿典型临床特征主要为特殊面容（眼距宽、双眼突出、鼻梁低平、舟状颅、耳位低、上唇短、下颌前突）。经全外显子组测序结果显示FGFR2基因发生突变,染色体位置（chr10:123276891）,核酸改变（c.1026(exon8)C>G）,氨基酸改变（p.Cys342Trp,NM＿000141）。结论 该患儿具有典型的临床特征和基因检测结果,支持诊断Crouzon综合征。     

Pierre Robin综合征1例并文献复习

Pierre obin综合征是由Pierre obin于1923年提出并以他的名字命名的一种先天性异常综合征。本病发病率约占新生儿的五万分之一。国内报道根据手头资料有沈氏等4篇，但多为个案报告，近年我们收治了1例，并查阅有关文献，报告如下。     

儿童滤泡淋巴瘤1例报道及文献复习

目的 探讨儿童型滤泡性淋巴瘤(pediatric folliculaRlymphoma,PFL)的临床病理特征,提高对PFL的认识和病理诊断水平.方法 对1例PFL进行临床表现分析、对其组织病理学和免疫组织化学染色进行观察.结果 患儿男,17岁.发现右侧耳屏前生长缓慢的无痛性肿块1年.病程中无发热、皮疹、消瘦等症状.临床分期为Ⅰ期.镜下:淋巴结结构破坏,滤泡部分区域相互拥挤,背靠背.滤泡中心有两种细胞组成,一种数量较少的中心细胞,另一种数量较多的中心母细胞.另外在滤泡中心可见到成对出现的滤泡树突细胞.肿瘤细胞表达CD20、CD79α、bcl-6,而bcl-2阴性.滤泡树突细胞表达CD21、CD23.淋巴细胞克隆性基因重排发现有IgH基因重排,EB病毒原位杂交阴性.结论 发生于儿童的滤泡性淋巴瘤(folliculaRlymphoma,FL)较少见,组织学上具有明显的滤泡结构.临床分期多为Ⅰ期,组织学分级为较高级别.其临床表现、预后与成人型FL有较大差别.     

Sweet综合征并发结节性红斑1例并文献复习

对1例同时发生的Sweet综合征与结节性红斑病例进行报道。患者女,43岁,咽痛、发热20余天,伴四肢皮疹半月。查体：眼睑结膜、面色苍白。双手背及前臂伸侧可见边缘突起的淡红色斑疹,有触痛,有假水泡形成,表面有痂皮,大小<2cm×3cm,呈圆形或椭圆形。双侧胫前皮肤广泛发红、水肿,其间可见数枚大小不等的红色结节。直径1~3cm,质较硬,触痛,无溃破及渗出。皮损病理：上肢皮肤乳头层及真皮层水肿,可见灶状淋巴细胞及大量炎细胞浸润,可见核碎。下肢真皮浅层、深层血管周围及脂肪间隔淋巴样细胞浸润。诊断：Sweet综合征合并结节性红斑。     

膝关节旁儿童纤维性错构瘤1例并文献复习

通过对1例儿童膝关节旁纤维性错构瘤的组织病理及临床表现进行观察,并复习相关文献.最终依靠病理结果确定本例为膝关节旁软组织内罕见的错构瘤.组织学上,肿瘤由束状排列的长梭形细胞、幼稚的未分化间叶细胞和成熟的脂肪组织不同比例组成.免疫组织化学上,幼稚的间叶细胞表达CD34,而梭形细胞表达平滑肌肌动蛋白(smooth muscle actin,SMA).儿童膝关节旁纤维性错构瘤是一种罕见的原发性软组织良性病变,发病缓慢,容易误诊,通过完整切除肿瘤,预后良好.     

Kartagener综合征一例并文献复习

目的探讨Kartagener综合征的临床特点、诊断标准,以提高对Kartagener综合征认识。方法 Kartagener综合征1例。患儿,女,10岁余。因反复咳嗽1年,咯血4次入院。回顾性分析该患儿临床资料,检索国内外文献,进行总结分析。结果患儿隐匿起病,主要表现为反复咳嗽,咳脓痰,伴咯血。CT示双肺支扩伴感染,全内脏反位,鼻窦炎。经抗感染对症治疗1周后,临床症状消失出院。检索国内外文献发现,Kartagener综合征以全内脏反位,支气管扩张,副鼻窦炎三联征为诊断标准。治疗以对症治疗为主。结论 Kartagener综合征是一种罕见的常染色体隐性遗传病,加强对该病的认识,有利于提高对该病的诊断率,减少误诊率。对该病的致病基因、机制的进一步研究,可能提供更好的诊断和治疗方法。     

先天性束带综合征一例并文献复习

目的提高对先天性束带综合征的认识水平。方法通过回顾性分析本科收治的先天性束带综合征1例和复习先天性束带综合征的文献5篇36例,共37例的临床资料。结果先天性束带综合征为先天畸形,是肢体发育中的异常,部位多在小腿,前臂,足趾,手指;治疗行环束带切除及皮瓣Z形缝合,术后预后好。结论先天性束带综合征临床少见,以肢体远端为多见,及早行手术治疗,术后预后好。     

Efficacy of flecainide in bidirectional ventricular tachycardia and tachycardia-induced cardiomyopathy with Andersen-Tawil syndrome

Andersen-Tawil syndrome is a rare autosomal dominant genetic or sporadic disorder characterized by periodic paralysis, ventricular arrhythmias and dysmorphic features. Ventricular arrhythmias can include frequent premature ventricular complex, polymorphic ventricular tachycardia, and less frequently bidirectional ventricular tachycardia. Left ventricle function has been reported in only a few individual cases of Andersen-Tawil syndrome. A 14-year-old female patient was referred to our clinic from another center with documented arrhythmia and left ventricular systolic dysfunction. Andersen-Tawil syndrome was suspected and the diagnosis was confirmed after detection of a previously unreported mutation in children. We report the successful use of flecainide in bidirectional ventricular tachycardia and tachycardia-induced cardiomyopathy in a case of Andersen-Tawil syndrome associated with a novel mutation.     

The costello syndrome: Report of a case and review of the literature

Summary A 5-year-old girl with the Costello syndrome is reported. Her clinical manifestations included growth and developmental delay, a distinct facial appearance with sparse and curly hair, nasal papillomata, and dark loose skin of the hands and feet. These manifestations, especially nasal papilloma, an age-dependent anomaly, are distinct in the Costello syndrome.     

Genotype-phenotype correlations of KCNJ2 mutations in Japanese patients with Andersen-Tawil syndrome

Andersen-Tawil syndrome (ATS) is a rare inherited disorder characterized by periodic paralysis, mild dysmorphic features, and QT or QU prolongation with ventricular arrhythmias in electrocardiograms (ECGs). Mutations of KCNJ2, encoding the human inward rectifying potassium channel Kir 2.1, have been identified in patients with ATS. We aimed to clarify the genotype-phenotype correlations in ATS patients. We screened 23 clinically diagnosed ATS patients from 13 unrelated Japanese families. Ten different forms of KCNJ2 mutations were identified in the 23 ATS patients included in this study. Their ECGs showed normal QTc intervals and abnormal U waves with QUc prolongation and a variety of ventricular arrhythmias. Especially, bidirectional ventricular tachycardia (VT) was observed in 13 of 23 patients (57%). Periodic paralysis was seen in 13 of 23 carriers (57%), dysmorphic features in 17 (74%), and seizures during infancy in 4 (17%). Functional assays for the two novel KCNJ2 mutations (c. 200G>A (p. R67Q) and c. 436G>A (p. G146S)) displayed no functional inward rectifying currents in a heterologous expression system and showed strong dominant negative effects when co-expressed with wild-type KCNJ2 channels (91% and 84% reduction at -50 mV respectively compared to wild-type alone). Immunocytochemistry and confocal imaging revealed normal trafficking for mutant channels. In our study, all of the clinically diagnosed ATS patients had KCNJ2 mutations and showed a high penetrance with regard to the typical cardiac phenotypes: predominant U wave and ventricular arrhythmias, typically bidirectional VT.     

Goldenhar综合征一例报道及文献复习

目的探讨Goldenhar综合征的发病机制、临床表现、诊断及治疗,以提高,临床医生对本病的认识。方法报道一例Goldenhar综合征患儿的临床资料,并复习通过文献数据库检索的相关文献。结果Goldenhar综合征病因尚不清楚,临床表现具有高度多样性,包括眼部畸形、耳部畸形、颜面畸形、脊柱异常、心脏及其它脏器等的发育缺陷;诊断主要依靠特征性的临床表现及头颅、脊柱的影像学检查;治疗以整形外科手术为主,如无合并严重脏器畸形,一般预后良好;产前胎儿超声对产前诊断有一定帮助。结论Goldenhar综合征是一种涉及全身多个器官系统的先天性畸形,详细的体格检查,并进行影像学检查,避免因诊断不全而延误对患者进行及时的诊治非常重要。     

Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome

Background

Andersen‐Tawil syndrome (ATS) is a rare inherited disorder, characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic features, and is caused by mutations in the gene KCNJ2, which encodes the inward rectifier potassium channel, Kir2.1. This study sought to analyse KCNJ2 in patients with familial ATS and to determine the functional characteristics of the mutated gene.

Methods and results

We screened a family with inherited ATS for the mutation in KCNJ2, using direct DNA sequencing. A missense mutation (T75R) of Kir2.1, located in the highly conserved cytoplasmic N‐terminal domain, was identified in three affected members of this family. Using the Xenopus oocyte expression system and whole cell voltage clamp analyses, we found that the T75R mutant was non‐functional and possessed a strong dominant negative effect when co‐expressed with the same amount of wild type Kir2.1. Transgenic (Tg) mice expressing the mutated form of Kir2.1 in the heart had prolonged QTc intervals compared with mice expressing the wild type protein. Ventricular tachyarrhythmias were observed in 5 of 14 T75R‐Tg mice compared with 1 of 7 Wt‐Tg and none of 6 non‐transgenic littermates. In three of five T75R‐Tg mice with ventricular tachycardia, their ECG disclosed bidirectional tachycardia as in our proband.

Conclusions

The in vitro studies revealed that the T75R mutant of Kir2.1 had a strong dominant negative effect in the Xenopus oocyte expression system. It still preserved the ability to co‐assemble and traffic to the cell membrane in mammalian cells. For in vivo studies, the T75R‐Tg mice had bidirectional ventricular tachycardia after induction and longer QT intervals.     

Silver-Russell综合征病例报道一例并文献复习

目的通过报道罕见的Silver-Russell综合征病例1例,并文献复习,了解该疾病的研究进展。方法对1例Silver-Russell综合征患儿的临床表现、实验室检查进行观察与分析并复习相关文献。结果确诊Silver-Russell综合征1例。结论 Silver-Russell综合征临床极少见,临床有遇到（1）宫内及生后生长发育迟缓;（2）典型面部特征：相对巨颅、三角脸等;（3）躯体不对称畸形;（4）喂养困难的患儿应警惕本病可能。本疾病临床表现非特异性,临床诊断困难,对高度可疑本病的患儿应行基因检查,一旦确诊应尽早采取重组人生长激素（GH）替代治疗等综合治疗,以改善患儿生存质量。     

Cushing's syndrome and nocardiosis associated with a pulmonary carcinoid tumor: Report of a case and review of the literature

Ectopic hormone production is an uncommon complication of neoplastic lung disease. Rarely, patients may present with signs and symptoms of systemic endocrine dysfunction related to a hormone‐secreting tumor. Bronchopulmonary carcinoids are the most common neoplasm implicated in ectopic ACTH‐dependent Cushing's syndrome. Persistent hypercortisolism, such as that which occurs in Cushing's syndrome, causes immunosuppression and makes patients vulnerable to opportunistic infections. We present a case of a 42‐year‐old woman diagnosed with ACTH‐dependent Cushing's syndrome which was originally thought to stem from a pituitary lesion as interpreted on magnetic resonance imaging. Her symptoms persisted after undergoing hypophysectomy, and further work‐up involving a fine needle aspiration of the left lung revealed an ACTH‐producing carcinoid tumor. Before treatment could be administered, the patient developed several new suspicious nodules in the left lung that were shown by fine needle aspiration to be infectious in nature. A Gram stain revealed numerous Gram positive branching organisms, and culture of the specimen grew Nocardia asteroides. Her pulmonary infection was treated with antibiotics and she underwent successful ablation of the carcinoid tumor. Diagn. Cytopathol. 2011. © 2010 Wiley‐Liss, Inc.     

Duplication 3p syndrome: Report of a new case and review of the literature

A review of the 17 previously reported cases of duplication 3p and study of a new patient who has a duplication of the chromosome segment 3p21→pter show a remarkably consistent phenotype among these patients and suggest some generalizations about prognosis. The manifestations include low birth weight, short stature, microcephaly, characteristic “square” face with temporal indentations, hypertelorism and/or telecanthus, epicanthus with a broad nasal bridge and large nasal tip, and down-turned corners of the mouth. Cleft lip/palate and eversion of the lips are common. The jaw is typically small and receding and the neck short. Congenital heart disease, gastrointestinal malformations, abnormalities on intravenous urography, and defective masculinization of the male infants are frequently observed. A predominance of whorls is present on the fingers. Nearly half of the cases died before 6 months. All affected children surviving beyond 1 year have been mentally retarded.     

Short rib-polydactyly syndrome,type 3 with chondrocytic inclusions: Report of a case and review of the literature

A newborn with severely shortened ribs, short limbs, and postaxial polydactyly died shortly after birth. Postmortem roentgenograms established the diagnosis of type 3 short rib-polydactyly (SRP) syndrome as described by Naumoff and associates. Histopathologic study showed the chondrocytes to contain previously undescribed cytoplasmic inclusion bodies that were PAS-positive and diastase-resistant. The material appeared by staining reactions to be a glycoprotein that was seen electron microscopically to accumulate within dilated cisterns of rough endoplasmic reticulum. Similar cytoplasmic inclusions have not been seen in other short rib-polydactyly syndromes, including SRP types 1 and 2, Jeune syndrome, and Ellis-van Creveld syndrome. It is often difficult to differentiate cases of type 3 and type 1 (Saldino-Noonan) syndrome, and in the past the diagnosis has sometimes been confused. A review of previously reported cases showed that type 3 syndrome rarely (1 in 13) had cloacal developmental abnormalities, which are invariably present in patients with type 1 syndrome. Type 3 is also associated with a lower incidence of congenital heart disease, and cardiac malformations, when present, differ from those associated with type 1 syndrome. Both type 3 and type 1 SRP syndromes are transmitted in autosomal recessive fashion. Type 3 SRP syndrome has had an equal sex distribution, although type 1 has so far been reported to occur only in girls. Further investigation with additional patients is necessary to verify the above preliminary findings.