A 21-year-old Chinese gentleman with no known medical illness, presented with a history of right painless blurring of vision with central scotoma of two weeks duration. He also had a history of multiple episodes of seizures prior to presentation. Visual acuity was 1/60 with unremarkable anterior segment findings and no relative afferent pupillary defect. Fundus examination of the right eye revealed dilated and tortuous retinal veins with multiple retinal capillary hemangiomas and sub retinal hard exudates at the macula with edema. A diagnosis of Von Hippel Lindau disease was made when a posterior fossa mass suggestive of hemangioblastoma with obstructive hydrocephalus was seen on computed tomography of the brain. Craniotomy with nodule excision was performed. The retinal capillary hemangiomas were treated with the combination of laser photocoagulation and intravitreal Ranibizumab injections. Visual acuity subsequently improved to 6/36.
Hemangioblastoma ; von Hippel-Lindau Disease

Humans ; von Hippel-Lindau Disease ; pathology

No abstract available.
Cystadenoma, Papillary* ; Fallopian Tubes* ; Female ; von Hippel-Lindau Disease*

A rare case of multiple supratentorial and infratentorial hemangioblastomas in a 50-year old man is presented. There were neither manifestations of visceral tumors nor familial history. The two tumors were totally removed in two sessions and the diagnosis in both tumors were hemangioblastomas.
Diagnosis ; Hemangioblastoma* ; Humans ; Middle Aged ; von Hippel-Lindau Disease

OBJECTIVE: Spinal cord hemangioblastomas are rare tumors. Despite their benign, slow-growing nature, they can cause severe neurological consequences. The purpose of this study was to evaluate variable factors, including clinical features, tumor findings, the extent of resection, and its recurrence or progression, which determine postoperative functional outcomes. METHODS: This study included sixteen patients at our institute who underwent microsurgical resection for sporadic spinal intramedullary hemangioblastomas and spinal intramedullary hemangioblastomas associated with von Hippel-Lindau (VHL) disease, between June 2003 and March 2012. RESULTS: A total of 30 operations were performed. Total resection (TR) of the tumor was achieved in 10 patients, and subtotal resection (STR) was achieved in 6. Postoperatively, the initial presenting symptoms were improved in 18.7% of the patients and were unchanged in 56.3%, but 25% were worse. Stable postoperative neurological functions were found in 83% of patients with preoperative McCormick grade I, and TR was achieved in 75% of these patients. In the STR group, poorer neurological status was observed in one patient, despite multiple operations. There were no poorer outcomes in the four cases of VHL disease. Various factors were analyzed, but only a correlation between the pre- and postoperative neurological status was verified in the TR-group patients. CONCLUSION: Preoperative focal neurological impairment and meticulous microsurgical manipulation may be predictors of favorable outcomes for solitary hemangioblastomas. In addition, the preservation of function is more important than the extent of resection in VHL disease.
Hemangioblastoma ; Humans ; Recurrence ; Spinal Cord ; von Hippel-Lindau Disease

Conus medullaris hemangioblastoma is very rare. We report a hemangioblastoma which was removed after embolization in conus medullaris. It was associated with syringomyelia from cervical cord to conus medullaris. There was no manifestation of von Hippel-Lindau disease. The literature on conus medullaris hemangioblastoma is reviewed and the mechanism of the syringomyelia associated with the hemangioblastoma is discussed.
Conus Snail* ; Hemangioblastoma* ; Syringomyelia ; von Hippel-Lindau Disease

OBJECTIVE: To detect VHL gene mutation in a pedigree affected with von Hippel-Lindau syndrome (VHL). METHODS: Clinical data of the pedigree was reviewed. Patients were subjected to Sanger sequencing to detect mutation of the VHL gene. Structure of pVHL was predicted by 3D modeling using the swiss-model. RESULTS: A novel c.426delT(p.V142fs) [NM_000551] mutation was found in exon 2 of the VHL gene. 3D modeling suggested that the alpha-structure of pVHL is completely absent. CONCLUSION The novel c.426delT(p.V142fs) mutation probably underlies the VHL in this pedigree.
DNA Mutational Analysis ; Exons ; Humans ; Mutation ; Pedigree ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder and its clinical manifestation including haemangioblastomas of the central nervous system, renal cell carcinoma, haeochromocytomas, and pancreatic cyst. The deletion, mutation and promoter methylation of VHL gene can cause VHL disease. Swine is considered as an ideal model for human disease because of its physiological and anatomical similarity to human. We cloned pig VHL gene that is 2 725 bp in length. VHL highly expressed in adrenal gland, liver, pancreas, heart and testis. We designed 5 shRNAs and screened the most effective interference RNA fragment with a knockdown efficiency of 72%. Porcine embryonic fibroblasts stably transfected with pGenesil-shRNA vector were used as donor cells for nuclear transfer and there was no significant difference of embryo development compared with the control group. Moreover, VHL was efficiently knocked-down with efficiency of 71% in porcine cloned blastocyst, these results lay a solid foundation for constructing the VHL knock-down model of pig.
Animals ; Cloning, Molecular ; Disease Models, Animal ; Embryo, Mammalian ; Gene Knockdown Techniques ; Swine ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

BACKGROUNDVon 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.

METHODSNine 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).

RESULTSThe 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.

CONCLUSIONSGenetic 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.

Asian Continental Ancestry Group ; DNA Mutational Analysis ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

OBJECTIVEEndolymphatic sac tumors (ELSTs) are rare in the general population with much higher prevalence in von Hippel-Lindau(VHL) disease. The purpose of this study is to present two cases of endolymphatic sac tumor with VHL disease with analysis of VHL gene and to explore their association with VHL disease using molecular analysis.

METHODSClinical data of these two patients from different VHL families were studied. DNAs extracted from peripheral bloods were amplified by the polymerase chain reaction using oligonucleotide primers corresponding to the VHL gene, then compared the mutations with the Human Gene Mutation Database.

RESULTSIn case 1, 6 family members were enrolled in the study. Among them, three had been identified to have a germline missense point mutation at codon 194 of the VHL gene exon 1 (p.S65W). The little sister of the patient (case 1) underwent vitrectomy for retinal hemangioblastoma 5 years ago in another hospital. The mother of the patient (case 1) was further diagnosed to have a cerebellar hemangioblastoma and renal carcinoma in the following physical examination. Case 2 with her parents were also tested. Codon 499 of the VHL gene exon 3 (p.R167W) were detected in case 2 and her mother, but the mother refused further examination.

CONCLUSIONSThe genetic diagnosis plays an important role in early detection of symptomatic patients and suspected patients. Clinical screening for members of the VHL families, and close follow-up of carriers allow an early detection of tumors and the metastasis, which is the most common cause of death of these patients.

Adolescent ; Adult ; DNA Mutational Analysis ; Ear Neoplasms ; complications ; genetics ; Endolymphatic Sac ; Female ; Humans ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; complications ; genetics