Analysis of characteristics of pedigrees with von Hippel-Lindau disease / 中华泌尿外科杂志

ABSTRACT

Objective To discuss the clinical characteristics of yon Hippel-Lindau (VHL)syndrome and the significance of genetic test for this disease.Methods Patients with VHL disease from 3 different families were reviewed from August 1985 to October 2017.The study was including clinical family survey and VHL-gene test on phylogenetic level.Totally 21 family members from 3 families were investigated,consisting of 14 males and 7 females with average age of 48.6 (5-70)years when analyzed.There were 8 patients with VHL disease comprising 5 males and 3 females with average onset age of 31.5 (9-67) years.Results The proband of pedigree one (VHL-Ⅱ C) was diagnosed as pheochromocytoma (PHEO) of right adrenal gland at 18 years old and underwent adrenalectomy,and her son was diagnosed with PHEO of bilateral adrenal glands with diagnostic age of 9 years old and received bilateral adrenalectomy sequentially.Her niece was diagnosed as PHEO of bilateral adrenal glands at 28 years old and received bilateral adrenal-sparing surgery simultaneously.Genetic analysis revealed a heterozygous mutation located at the third exon of the VHL gene (c.482G ＞ A).The proband of pedigree two (VHL-Ⅱ B) was diagnosed as right PHEO,bilateral multiple renal clear cell carcinoma (RCC),multiple pancreatic cysts and bilateral epididymal cystadenoma,and he received right adrenalectomy,right partial nephrectomy at 25 years old and delayed eystadenoma excision.His younger brother was also diagnosed as bilateral,pancreatic multiple cysts and bilateral epididymal nodules at 27 years old,and underwent right radical nephrectomy.Genetic analysis revealed a heterozygous mutation located at the first exon of the VHL gene (c.233A ＞ G).The proband of pedigree three (VHL-Ⅱ B) was diagnosed with central nerve system hemangioblastomas (CNS-HB) at 35 years old and received external beam radiotherapy.His elder sister was diagnosed as CNS-HB at 43 years old and received surgery.His father was diagnosed as right PHEO,bilateral RCC,bilateral multiple renal and pancreatic cysts and pancreatic neuroendocrine tumors at 67 years old.He received right adrenalectomy and partial nephrectomy.Genetic analysis showed a heterozygous mutation located at the third exon of the VHL gene(c.500G ＞ A).In addition,two cases (F2-Ⅲ 1 and F3-ⅣV1) were found to be asymptomatic VHL gene carriers by genetic screening.8 patients were followed up for an average of 9.8 (2-32) years.The symptoms were stable and no local recurrence or distant metastasis was found after operation.In this study,no CNS-HB was found in patients within family 1 and family 2,and RCC in 3 patients within family 2 and family 3 were low grade.Conclusions The clinical manifestations of VHL disease are diverse.RCC and CNS-HB are not present in all patients with the disease.PHEO is the only manifestation in patients with VHL-ⅡC.It is necessary to inform the members of VHL syndrome family for genetic test.Genetic test combined with clinical screening can facilitate differential diagnosis for VHL syndrome and other hereditary urological diseases.