家族性Von Hipple-Lindau病3例并文献复习

目的 对von Hipple-Lindau病(VHL病)进行系统探讨,提高临床医生对该病的认识水平.方法 通过临床典型3例家族性后颅窝-椎管内发病的VHL病罕见病例结合文献复习,讨论VHL病的诊断治疗特点.结果 VHL病需根据患者的临床表现及基因检测结果做出诊断,突变基因的DNA分析要明显优于基于临床表现所进行的诊断....     

遗传性多器官肿瘤综合征应引起重视——龚侃教授谈VHL病

日前,北京大学第一医院泌尿外科龚侃教授向记者介绍了遗传性多器官肿瘤综合征,即VHL病(von Hippel-Lindau disease)的临床情况.龚侃指出,VHL病是由VHL基因突变或启动子高甲基化导致的常染色体显性遗传病,表现为全身多器官的肿瘤综合征.VHL病临床表现复杂,通常累及多个脏器.然而,目前国内很多医生对VHL病的整体性认识不足,往往只针对某一系统的病灶进行治疗,继而不能给予准确诊断和合理治疗.因此,广大医务工作者对VHL病应有更为深入的了解,更好地开展疾病的筛查、诊断和治疗.     

Von Hippel-Lindau(VHL)病诊断与治疗(附3例报告)

目的提高Von Hippel-Lindau病(VHL)并发泌尿系疾病的诊断和治疗水平。方法回顾分析3例VHL病并发泌尿系疾病患者临床资料并结合文献复习讨论。2例为VHLⅠ型,1例为VHLⅢ型。结果1例VHLⅢ型随访3个月。肿瘤无复发。2例VHLⅠ型,其中1例随访26个月未见肿瘤复发,另1例因肾癌晚期远处转移致多脏器功能衰竭术后4个月死亡。结论肾癌、肾囊肿、嗜铬细胞瘤是VHL病在泌尿系的表现而肾癌具有多中心、双侧发病、易复发等特点。薄层CT是主要的诊断和随访手段。手术治疗方式包括双肾切除,肾肿瘤剜除和肾部分切除等,保留肾单位术后应密切随访,及时发现再发的病变。     

Von Hippel-Lindau病15例影像学分析

目的:探讨Von Hippel-Lindau disease(VHL)病临床和影像学特点。方法:回顾性分析日本横滨市立大学附属医院2001～2006年间经手术和病理确诊的15例Von Hippel-Lindau disease(VHL)病的临床和影像学资料并且复习相关文献。结果:本病好发男性青壮年,47%(7/15)可追溯到家族史,所有病例有血管母细胞瘤,绝大多数发生在小脑(13/15),为实性小结节或者囊实性结节,部分见于脊髓;视网膜血管瘤占40%(6/15);绝大多数合并内脏囊肿,包括肝脏、胰腺和肾脏,占87%(13/15);肾癌占60%(9/15),可单侧或者双侧;嗜铬细胞瘤占13%(2/15)。结论:VHL病是家族遗传性多系统肿瘤综合征,熟悉其临床和影像学表现有助于正确的诊断。     

家族性延髓血管母细胞瘤3例报告

目的 探讨家族性延髓血管母细胞瘤的诊断和治疗.方法 分析一个家系3例延髓血管母细胞瘤的临床资料和手术疗效,结合文献讨论.结果 本家系确诊VHL病[Von Hippel-Lindau Syndrome(VHL ),"希佩尔-林道综合征"].3例肿瘤全部切除,随访6～48个月,3例KPS(karnofsky评分)均>90分.结论 延髓血管母细胞瘤诊断主要依靠CT、MRI,基因检测对VHL病诊断有重要价值.显微手术技巧可显著提高本病的疗效.围术期控制"正常灌注压突破综合征".及时发现和处理相关并发症对本病的预后有重要意义.     

VHL综合征基因研究进展

Von Hippel-Lindau (VHL)综合征是一种常染色体显性遗传病。人们发现VHL基因是一个抑癌基因,VHL综合征是由VHL基因突变引起。随着基因技术的发展,VHL基因检测诊断疾病已经越来越重要,同时对VHL综合征的治疗也提供了一条新的途径和广阔的应用前景。     

VHL病伴发双侧肾癌3例报告并文献复习

目的 初步探讨以冯·希佩尔·林道(Von Hippel-Lindau,VHL)病并发双侧肾癌的发病特点、诊断及治疗.方法 回顾分析2007年2月-2011年6月解放军第309医院收治的3例VHL病并发双侧肾癌的患者,并结合文献复习.结果 3例中1例有家族史,先后行右侧保留肾单位手术,左侧腹腔镜下肾癌根治性切除,病理提示为透明细胞癌,术后规律血液透析,等待肾移植;另2例为多发病变,双侧肾癌伴双侧多发肾囊肿,2例均选择双侧保留肾单位手术和肾囊肿去盖术,术后病理提示为透明细胞癌,肾功能正常.结论 VHL病肾癌有独特的临床特征,不同于散发性肾癌,诊断主要依靠MRI和CT;治疗主要依靠手术,术后易复发,因累及多脏器,需要多学科给予综合治疗.     

Von Hippel—Lindau病1例

Von Hippel-Lindau(VHL)病是一种少见的常染色体遗传性疾病,患者常以中枢神经系统症状前来就诊,神经外科医生通常会诊断为血管网织细胞瘤.但事实上有20% -30%的患者还合并有其他系统的肿瘤.我们报道此病例是希望能提高大家对Von Hippel-Lindau(VHL)病的认识,重视其遗传特性,做好患者家属的随访工作.     

VHL基因研究与中枢神经系统血管网状细胞瘤

希佩尔-林道病(Von Hippel-Lindau,VHL)是一种常染色体显性遗传病,以发生中枢神经系统和其他内脏器官多系统肿瘤为特征。VHL基因是重要的肿瘤抑制基因,VHL基因突变导致VHL蛋白及pVHL-ElonginC-Elongin B-Cul2复合物形成障碍,引起形成富血管肿瘤重要步骤的缺氧诱导因子功能障碍,导致肿瘤发生。发生中枢神经系统血管网状细胞瘤是VHL病中的常见事件。     

VHL综合征的影像学诊断

VHL综合征是一种常染色体显性遗传性疾病,通常多脏器患病,影像检查是发现病变的主要手段。本文介绍了VHL综合征的影像学表现,诊断标准和检查时机,重点比较了不同影像学方法应用于VHL综合征的优势和限制。     

Von Hippel-Lindau综合征4例影像学表现和遗传史回顾及文献复习

目的总结Von Hippel-Lindau(VHL)综合征的影像学表现和诊断方法。方法回顾分析4例vHL综合征患者的影像学、家族遗传史和其他临床资料,结合复习相关文献,探讨该少见遗传病的诊断方法。结果本组4例患者,男1例,女3例,年龄28⁴1岁,中位年龄34.3岁,影像学均表现为胰腺多发囊实性占位和双肾多发囊实性肿物。既往都有脑内肿瘤手术史和家族多人发病的遗传史,符合Maher等提出的该综合征诊断标准。结论 VHL基因不同突变类型导致不同表现型,临床表现形式复杂多样,认识VHL综合征的影像特征,结合临床病史可以明显提高其诊断水平。     

Genetic study of a large Chinese kindred with von Hippel-Lindau disease

Background Von HippeI-Lindau (VHL) disease is a heraditary cancer syndrome caused by germline mutations of the VHL tumor on the suppressor gene. This study was to show the clinical characteristics of a large Chinese kindred with yon HippeI-Lindau disease and to evaluate the role of the genetic test of VHL disease in the diagnosis of VHL disease and clinical screening of members of the VHL disease family.Methods DNA extracted from peripheral blood was amplified by PCR to three exons of the VHL gene in 27 members of a large kindred with VHL disease. PCR products were directly sequenced. The involvements of multi-organs in the kindred with VHL disease were confirmed by history taking and radiography.Results Of 47 members in the four generations of the kindred, 18 members were diagnosed as having VHL desease. Clinical manifestations of 18 patients included: central nervous system (CNS)hemangioblastoma (5), renal cell carcinoma and CNS hemangioblastoma (3), renal cell carcinoma and retinal angioma (3), renal cell carcinoma and multiple pancreatic cysts (1), renal cell carcinoma and retinal angioma and multiple pancreatic cysts (2), renal cell carcinoma and CNS hemangioblastomas and multiple pancreatic cysts (1), and multiple pancreatic cysts and multiple renal cysts (1), multiple pancreatic cysts (2). The common lesions of the 18 patients were renal cell carcinoma (55.6%), CNS hemangioblastoma (50.0%), retinal angioma (27.8%), and multiple pancreatic cysts (38.9%). Among the 27 members who volunteered for genetic analysis, 15 members including 9 affected family patients and 2 asymptomatic patients and 4 carriers, who are still alive, presented a codon 78 from Asn to Ser change at nucleotide 446 (A→G) in exon 1. Four members were carriers with the same VHL gene mutation. Two asymptomatic patients were initially diagnosed by genetic testing and subsequently confirmed radiologically and surgically. Members without gene mutation had no clinical evidence of VHL disease.Conclusions The large Chinese kindred with VHL disease was classified as type I . The main characteristics in the kindred were higher incidence of renal cell carcinoma and lower incidence of retinal angioma. Genetic test plays an important role in early detecting asymptomatic patients and the carriers in clinical screening of members of the families with VHL disease. It is also important to prevent the transmission of VHL disease to their offsprings in the kindred.     

Imaging manifestations of von Hippel-Lindau disease: a report of 3 casesImaging manifestations of von Hippel-Lindau disease: a report of 3 cases

Von Hippel-Lindau (VHL) disease is an autosomal dominant here ditary familial neoplasm syndrome characte rized by development of a variety of benign and malignant tumors in multiple organ systems,such as the brain,kidney,pancreas,adrenalgland,and epididymis,with aprev a lence of one in 39000- 53000.1 4 Hallmarks of the condition in clude retinal angiomas,hem angioblastomas of the cerebellum and the spinal cord,renal cell carcinoma and cysts,and pheochrom ocytomas.In this article,we report imaging findings in three cases of VHLdisease.     

von Hippel-Lindau病三例并文献复习

目的:初步探讨VHL病的发病机制、诊断以及治疗。方法:回顾分析既往收治的3例VHL病人并结合文献复习。结果:3例患者中1例有家族史,另2例为多发病变,均未能全切。第1例患者鞍上无症状病变动态观察,第2例患者颈椎HB过小,动态观察,第3例患者一处病变位于颈椎腹侧,无法切除,其余病变全部切除。结论:本病诊断主要依靠MRI,治疗主要依靠手术,因累及脏器多,很难全部切除,易复发,愈后较差。     

Molecular basis of von Hippel-Lindau syndrome in Chinese patients

Background  Von Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.

Methods  Nine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).

Results  The nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G>T, was novel. The other seven VHL mutations, c.233A>G [p.Asn78Ser], c.239G>T [p.Ser80Ile], c.319C>G [p.Arg107Gly], c.481C>T [p.Arg161X], c.482G>A [p.Arg161Gln], c.499C>T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.

Conclusions  Genetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families. 

     

von Hippel-Lindau syndrome: molecular diagnosis of two Lebanese families and analysis of the genotype-phenotype correlation

The von Hippel-Lindau syndrome (VHL) is a dominantly transmitted hereditary disorder associating multisystemic tumors affecting mainly the central nervous system, the kidneys, the pancreas, as well as pheochromocytomas. Mutations of the tumor suppressor gene VHL on chromosome 3 are responsible for the disease. This article reports for the first time the study of two Lebanese VHL affected families, presenting particularly hemangioblastomas of the central nervous system. Two different mutations of the VHL gene, S65W and F76S, respectively identified in the two families, confirmed the clinical diagnosis of the patients. Molecular diagnosis was then performed for at risk members of these families. This article reveals the importance of molecular diagnosis for suspected patients and of presymptomatic diagnosis for at risk members, especially that a close follow-up of carriers allows an early detection of tumors and prevents the metastasis stage, the most common cause of death of these patients.     

嗜铬细胞瘤和副神经节细胞瘤分子生物学研究进展

嗜铬细胞瘤和副神经节细胞瘤中大约有10%属于遗传性疾病。遗传性嗜铬细胞瘤主要为多发性内分泌腺瘤病2型(MEN2)、von Hippel-Lindau病(VHL)、纤维神经瘤病Ⅰ型(NFⅠ)、遗传性副神经节瘤以及遗传性嗜铬细胞瘤。迄今为止,已了解的与嗜铬细胞瘤有关的基因为RET基因、VHL基因和SDHx基因。本文对上述基因以及散发的嗜铬细胞瘤分子生物学研究做一综述。     

结合临床特征探讨腹部超声在诊断Von-Hippel-Lindau综合征中的作用

目的 分析Von-Hippel-Lindau(VHL)综合征的临床特征,探讨腹部超声在诊断VHL综合征中的作用。方法 回顾性分析1994年1月至2017年12月在北京协和医院收治的35例VHL综合征患者的临床资料,包括首诊年龄、症状、体征、受累脏器、手术次数、检查方法等,分析腹部超声对诊断VHL综合征的作用。 结果 35例患者中,嗜铬细胞瘤(14例)及神经系统血管母细胞瘤(13例)为常见的首发肿瘤,神经系统血管母细胞瘤(21例)、嗜铬细胞瘤(19例)、肾癌(17例)及胰腺占位(15例)为常见的肿瘤。主要手术原因为神经系统血管母细胞瘤(22例次)、嗜铬细胞瘤(23例次)及肾癌(13例次)。33例患者腹部脏器受累,20例(60.6%)首次被腹部超声发现,其中6例为健康体检时发现。行肾上腺超声33次,27次诊断准确。行胰腺超声16次,13次诊断准确。行肾脏超声19次,8次诊断准确。结论 当超声发现肾脏、肾上腺、胰腺等部位的多发肿瘤时,超声医师要仔细询问家族史和神经系统疾病史,考虑VHL综合征的可能性。当临床提示存在VHL综合征时,超声能够发现及诊断腹部肿瘤,同时可以用于长期随访观察肿瘤的变化。超声是VHL综合征腹部疾病筛查和随诊的重要手段。     

Screening for von Hippel-Lindau disease by DNA polymorphism analysis.

OBJECTIVE--Von Hippel-Lindau (VHL) disease is a rare, inherited multisystem neoplastic disorder. There is no biochemical test available to distinguish VHL disease gene carriers from their healthy siblings. We evaluated DNA polymorphism analysis as a method for identifying disease gene carriers. DESIGN--Prospective comparison of the results of DNA analysis with a comprehensive clinical screening examination. SETTING--The Clinical Center of the National Institutes of Health. PATIENTS--Blood was collected from 182 members of 16 families with VHL disease. Forty-eight asymptomatic individuals, at risk of developing this hereditary illness (with an affected parent or sibling), were examined for occult disease at the Clinical Center of the National Institutes of Health and tested by DNA polymorphism analysis. RESULTS--DNA polymorphism analysis predicted nine disease gene carriers and 33 individuals with the wild-type (normal) allele among the 48 individuals at risk of developing VHL disease; the test was not informative in six individuals. All nine individuals predicted to carry the VHL gene had evidence of occult disease on clinical examination. There was no clinical evidence of VHL disease in 32 of 33 individuals predicted to carry the wild-type allele. CONCLUSIONS--DNA polymorphism analysis can identify individuals likely to carry the VHL disease gene among asymptomatic members of disease families. This technique serves to focus attention on those individuals who require periodic medical examination and may help to alleviate the morbidity and mortality associated with this disease.