Cornelia de Lange综合征首个国际共识的解读

Cornelia de Lange综合征（CdLS）是一种以严重神经发育障碍为主要表现的遗传综合征，临床表现为智力障碍、典型的面部特征、宫内和生后生长发育迟缓及多器官系统畸形等，发病率约1/10?000~1/30?000。2017年国际CdLS共识小组成立，并于2018年7月发表了国际上首个关于CdLS的共识“Diagnosis and management of Cornelia de Lange syndrome：first international consensus statement”（《Cornelia de Lange综合征的诊断和管理：第一份国际共识声明》）。该共识通过改良德尔菲法制定，对CdLS患儿的诊断和管理提出了若干指导性意见。该文对共识进行解读，旨在帮助临床医生早期识别、诊断、规范随访及管理CdLS患者。     

2例Cornelia de Lange综合征患儿NIPBL基因突变研究

两例患儿（1例男婴、1例女婴）均为婴儿期起病,均以生长缓慢为主诉就诊,均具有特殊面容如毛发浓密、弓形眉、连体眉,睫毛长且弯曲,以及短鼻、小下颌,患儿1伴有先心病（房间隔缺损、肺动脉狭窄）和特殊皮纹（通贯掌）,患儿2有腭裂、中重度耳聋。2例患儿的临床特点均提示Cornelia de Lange综合征。应用高通量基因捕获测序技术检测两例患儿Cornelia de Lange综合征的7个已知致病基因NIPBL、SMC1A、SMC3、HDAC8、RAD21、EP300和ANKRD11,Sanger测序法对突变基因进行分析和验证。2例均检测到NIPBL基因的新发突变,1例为移码突变：Exon 45 R2612fsX20（c.7834dupA）;另1例为无义突变：Q169X（c.505C > T）。2例患儿父母的NIPBL基因该位点正常,50例无关健康个体也未发现这两个位点的突变。     

SMC1A基因变异所致Cornelia de Lange综合征一例

患儿女,5月龄,因"10 d内抽搐5次"住院。特殊面容,浓眉、弓形眉、连心眉,睫毛长且弯曲,小下颌,肌张力略增高,大运动和精神发育落后。头颅磁共振成像示胼胝体变薄;视频脑电图示双侧前头部异常放电;家系全外显子组检测提示患儿存在SMC1A基因NM_006306:exon4:c.607A>G(p.K203E)杂合变异所致Cornelia de Lange综合征Ⅱ型。患儿SMC1A基因检测到的杂合变异c.607A>G是新发变异,在国内未见报道,扩大了SMC1A基因变异谱。     

De Lange �ۺ���1��

De Lange综合征,即德朗热综合征(精神发育阻滞伴有多种先天畸形)是一种少见遗传病。由Brachmann于1916年首次报道。国内报道很少。其发病率为1/3万至1/5万,无性别差异,患儿同胞发病率为2%～5%。现报道我院1例Cornelia de lange综合征病例。1病历摘要患儿女,8月龄,于2011-04-11因"生长发育落后8个月"于中山市博爱医院就诊收住院。患儿系第4胎第2产,孕8个月,家中顺产娩出,出生体重1.6kg。生后母乳、奶粉喂养,每次30mL,2～3h一次。体重增长缓慢,8月龄时体重4kg。患儿2月龄时会笑,4月龄能抬头,至来诊仍不会翻     

HDAC8基因变异所致Cornelia de Lange综合征1例报告

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.Y 225X)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。     

早产儿德朗热综合征一例

德朗热综合征又称为阿姆斯特丹侏儒症[1]、Cornelia deLange Syndrome,是一种多发性先天异常综合征.其特点是具有典型的面部特征,宫内生长发育迟缓,并可能出现多发畸形,存活者常有严重生长发育落后.     

力欣奇继续医学教育园地——思考病例系列（3）答案

正(病例见本期彩页)建议完善的检查:基因检测。检查结果:该患儿进行全外显子基因测序分析,提示NIPBL基因杂合变异,突变位点为c.5624TA(p.Ile1875Asn),该患儿父母均未携带该突变。该突变是一个未经报道的新发杂合变异,软件预测有致病性。诊断:德朗综合征(cornelia de Lange syndrome,CdLs)。CdLs是一种罕见的累及多系统的先天性疾病。该综合征主要临床表现为特殊面容、宫内或生后生长发育迟缓、认知障碍及多器官缺陷可能。已知的致病基因包括:NippedB相似基因(NIPBL)、SMC1A、SMC3、RAD21和HDAC8基     

儿童闭塞性细支气管炎

闭塞性细支气管炎（bronchiolitis obliterans,BO）是1901年德国病理学家Lange首次报道并命名的。从病理学角度,BO被定义为两种类型的支气管损伤：狭窄性细支气管炎和增殖性细支气管炎。从临床意义上讲,BO是一种与小气道炎症损伤相关的慢性气流阻塞综合征。各种因素导致的细支气管上皮细胞和上皮下结构的损伤和炎症,及机体对以上损伤和炎症的不正当修复是BO的发病原因。     

新生儿芬兰型先天性肾病综合征1例基因突变类型

目的探讨芬兰型先天性肾病综合征(CNF)患儿的NPHS1基因突变类型。方法回顾分析1例CNF患儿的临床资料,以及患儿及其父母的NPHS1基因检测结果。结果男性新生儿,34周早产,出生后呼吸困难,出生第3天出现尿糖、尿蛋白、血尿,临床确诊为先天性肾病综合征。患儿NPHS1基因出现2个杂合突变:c.1699??C,p.(Cys567Arg);c.3523_3524de1TT,p.(Leu1175Valfs)。其父亲携带c.1699??C,p.(Cys567Arg)杂合突变,母亲携带c.3523_3524de1TT,p.(Leu1175Valfs)杂合突变。结论 NPHS1基因的c.1699??C,p.(Cys567Arg);c.3523_3524de1TT,p.(Leu1175Valfs)突变可能引起CNF,其中c.1 699??C,p.(Cys567Arg)国内外未见报道。     

儿童闭塞性细支气管炎

闭塞性细支气管炎(bronchiolitis obliterans,BO)是1901年德国病理学家Lange首次报道并命名的.从病理学角度,BO被定义为两种类型的支气管损伤:狭窄性细支气管炎和增殖性细支气管炎.从临床意义上讲,BO是一种与小气道炎症损伤相关的慢性气流阻塞综合征.各种因素导致的细支气管上皮细胞和上皮下结构的损伤和炎症,及机体对以上损伤和炎症的不正当修复是BO的发病原因.这些因素包括感染、器官或骨髓移植、严重的皮肤黏膜过敏性疾病,如Stevens-Johnson 综合征、结缔组织病、吸入有毒物质、胃食管反流、药物不良反应等,在儿童多为感染后BO.临床表现为持续的咳嗽喘息,高分辨CT可见到马赛克灌注征、支气管壁增厚、支气管扩张等特征性改变,肺功能表现为阻塞性通气功能障碍.BO目前尚无有效的治疗方法,预后不良.     

Leigh's disease with clinical manifestations of Cornelia de Lange syndrome.

Leigh's disease was found postmortem in a 5-year-old girl who was diagnosed clinically as Cornelia de Lange syndrome at age 1 year. The child's neurological status began to deteriorate rapidly at age 4.5 years and she died suddenly 6 months later. Postmortem examination of the brain revealed bilateral necrosis of the hypothalamus, subthalamic nuclei, midbrain, pons, and medulla. Previous studies have linked Cornelia de Lange syndrome to hypothalamic lesions. This case demonstrates that Leigh's disease, which also damages the hypothalamus, could present with phenotypic features of Cornelia de Lange syndrome.     

Cornelia de Lange syndrome: a case study

Cornelia de Lange syndrome (CdLS) is a rare dysmorphogenic disorder characterized by growth retardation, severe cognitive limitations, distinctive facial features, and limb reduction anomalies recognizable at birth. Currently, no single criterion is diagnostic for CdLS, and misdiagnosis is not uncommon. Long-term management of the infant with CdLS requires a coordinated effort among many different specialists. This article presents a general overview of Cornelia de Lange syndrome. It concludes with a case study illustrating the many problems infants with CdLS may have and the great amount of teaching and support that is needed by families affected by CdLS.     

Cornelia de Lange syndrome associated with cecal volvulus: report of a case

Cornelia de Lange syndrome is known to be occasionally associated with gastrointestinal malformation. However, the occurrence of cecal volvulus in such anomalies is very rare. We report a 15-y-old Japanese boy with Cornelia de Lange syndrome associated with a cecal volvulus secondary to non-fixation of the cecum and ascending colon. The patient was admitted to our hospital because of abdominal pain and bilious vomiting. At emergent laparotomy, cecal volvulus with non-fixation of the ascending colon and cecum was diagnosed. Release of the cecal volvulus and the fixation of the cecum and ascending colon to the right retroperitonium were performed. The postoperative course was uneventful, except for sepsis caused by aspiration pneumonia soon after the operation. Conclusion: Clinicians treating patients with this syndrome should be aware that such patients may be at risk for developing severe gastrointestinal anomalies, including cecal volvulus.     

Radiological manifestations of the Cornelia de Lange syndrome

This paper describes the radiological findings obtained in 20 patients with the Cornelia de Lange syndrome. The pattern profiles of the hand skeleton were studied in these patients, using the method described by Poznanski et al. This study revealed a short first metacarpal bone, combined with relatively long third and fourth metacarpals, to be the most characteristic feature of the syndrome. No radiological characteristic was found to be pathognomonic of the syndrome, but the combination of a deformed proximal metaphysis of the radius with the above mentioned abnormality in the pattern profile of the hand is described as highly suggestive of the Cornelia de Lange syndrome.     

Aberrant course of the umbilical vein in a newborn with Cornelia de Lange syndrome

Congenital anomalies of the umbilical vein are rare. We describe an aberrant course of the umbilical vein discovered by identifying an unusual umbilical venous catheter course on abdominal radiography in a patient with Cornelia de Lange syndrome. The umbilical vein bypassed the liver to insert directly into a right pelvic vein. Use of the lateral abdominal radiograph and sonography were helpful in determining the catheter location after identifying the unusual course of the catheter on the frontal radiograph.     

Fatal sepsis associated with acute pancreatitis caused by Moraxella catarrhalis in a child.

We describe a 4-year-old boy with Cornelia de Lange syndrome who died of septic shock caused by Moraxella catarrhalis bacteremia. At autopsy there was evidence of acute hemorrhagic pancreatitis with abscesses. Gram-negative diplococci were seen histologically in the abscesses and pancreatic ducts.     

Microcephalic dwarfism with associated low amniotic fluid 5-hydroxyindole-3-acetic acid (5HIAA). Report of a case of Cornelia de Lange syndrome

A very low level of 5HIAA in the amniotic fluid was found in a microcephalic dwarf presenting subsequently with Cornelia de Lange syndrome. Since both the amount of amniotic fluid and the renal function after birth were normal this observation suggests that low amniotic fluid 5HIAA may be secondary to abnormalities in foetal neurological development.     

Anoxic-epileptic seizures in Cornelia de Lange syndrome: Case report of epileptic seizures induced by obstructive apnea

We describe epileptic seizures including status epilepticus provoked by recurrent obstructive apnea in a child with Cornelia de Lange syndrome. From the age of 10 months, this boy had recurrent respiratory infections with obstructive apnea leading to cyanosis and loss of consciousness. Approximately, 25% of apneas were followed by clonic jerks usually lasting 10 min, but once status epilepticus. He never had unprovoked epileptic seizures. At first he was diagnosed with symptomatic epilepsy and given carbamazepine and phenobarbital, without benefit. Significant improvement occurred after his mother was taught to extract mucus from his upper airways before obstruction occurred. He is no longer on anti-epileptic drugs. With this management, he had only one episode of obstructive apnea followed by an epileptic component.The events in this child were anoxic-epileptic seizures, that is, epileptic seizures triggered by syncopes. Anoxic-epileptic seizures have not previously been described in Cornelia de Lange syndrome. This case illustrates that, even when recurrent epileptic seizures occur in patients with known structural cerebral pathology, the diagnosis of symptomatic epilepsy should not be uncritically accepted.