Genetic features and surgical managements for von Hippel-Lindau disease type II

Abstract

Objective To improve the diagnosis and treatment of von H ippel-Lindau (VHL) disease.Methods The clinic data of one kindred with VHL disease type Ⅱ B was reviewed including clinical manifestation,imaging,pathology and therapy.A 40-year-old male complained of the left upper extremity numbness for 6 months,and a variety of visceral tumors were found 3 months ago.Contrast-enhanced MR imaging showed multiple brain tumors.CT showed left kidney tumor,pancreatic tumor,pars-aortic tumor and left adrenal tumor.Fundoscopy showed multiple retinal hemangioblastoma.PET-CT discovered abdominal multiple tumors.And pedigree analysis was to determine the family medical history,and 6 members got genetic screening.Results In the kindred with VHL disease type Ⅱ B,9 members (30％) out of 40members in 4 generations got the disease.Six members got genetic screening,and the result showed 5 (5/6) members had mutation.Three (3/5) members with 3 sites genetic mutation showed clinical manifestation,1 (1/5) members with 3 sites genetic mutation without clinical manifestation found brain tumors by MRI,and 1 ( 1/5 ) member with 1 site genetic mutation did not find disease by comprehensive checkup.The main mutation located at exon 1 in chromosome 3p25 of VHL gene.All mutation was hetcrozygous mutation.The 295,337 and 337 nucleotide thymine of the VHL gene were substituted by cytosine,cytosine and adenine,which made the 98th,112th and 112th tyrosine substituted by histidine and asparagines.One member with 1 site mutation had 98th tyrosine substituted by cytosine.The first operation was to remove brain tumor,and the second operation was to remove adrenal tumor,para-aortic tumor and renal tumor.Pathology of the brain tumors showed hemangioblastoma,and the retroperitoneal tumors were clear cell carcinoma,paraganglioma and pheochromocytoma.Followed up for 6 months after operation,no relapse occurred.Conclusions VHL disease is a relatively rare autosomal dominant disorder.Comprehensive management of patients should also include genetic counseling and screening for other manifestations of the disease process.Genetic testing might be helpful in early detection of asymptomatic VHL patients.Members having gene mutation should be followed up strictly.Surgical management of VHL disease should be decided on the base of comprehensive assess.Multiple lesions could be cut off in one operation.For patients with pheochromocytoma,pheochromocytoma shuld be handled first. Key words: Hippel-Lindau disease; Pedigree; Kindred; Surgical procedures, operative