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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2013, Vol. 7 Issue (3) : 378-385     DOI: 10.1007/s11684-013-0276-0
RESEARCH ARTICLE |
Epidemiological study of a von Hippel-Lindau family in northwest China
Jingyao Zhang1, Dapeng Wu2, Hong Ai3, Jigang Bai1, Shunbin Dong1, Qinling Yang1, Kai Qu1, Lei Zhou1, Xinsen Xu1, Chang Liu1()
1. Department of Hepatobiliary Surgery, the First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China; 2. Department of Urology Surgery, the First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China; 3. Department of Ultrasound, the First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China
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Abstract  

von Hippel-Lindau (VHL) disease is a rare, inherited neoplastic disease characterized by hemangioblastomas (HBL) of the central nervous system (CNS), retinal angiomas, renal cell carcinomas (RCC), pancreatic endocrine tumors (PETs), pheochromocytomas, paragangliomas, and visceral cysts. We encountered a large VHL family in northwest China and conducted a systematic screening of the family members based on their epidemiological and clinical characteristics. A self-designed questionnaire was used to collect the general sociodemographic and health information of the family members. For the preliminary family screening, physical examination and abdomen B ultrasonography were performed. The suspected patients were subjected to cranial computerized tomography and fundus examination. The clinical data of the patients with confirmed VHL disease were collected from hospital records. A total of 63 lineal descendants in six generations were observed in the family (generations O, A, B, C, D, E), including 9 dead suspected cases (6 males, 3 females) and 10 living cases (2 males, 8 females). Among the 10 living cases, 4, 2, 1, 3, 4, 8, and 2 manifested HBLs of the CNS, PETs, RCC, pancreatic cysts, renal cysts, pheochromocytomas (4 hemi and 4 bilateral), and paragangliomas, respectively. Data showed that the morbidity of VHL disease in generation C was lower than that in generation B, but the age of onset was younger. This study is the first to report VHL disease in northwest China and VHL-associated PET cases in Chinese. Therefore, follow-up checkups of the family should be focused on younger generations. Proper family screening protocols should be followed for the treatment of patients with VHL disease.

Keywords von Hippel-Lindau disease      epidemiology      family screening      pancreatic endocrine tumor     
Corresponding Authors: Liu Chang,Email:liuchangdoctor@gmail.com   
Issue Date: 05 September 2013
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-013-0276-0     OR     http://academic.hep.com.cn/fmd/EN/Y2013/V7/I3/378
Fig.1  Simple family genogram of the VHL family.
GenderC A (years)SymptomMarital statusBP (mmHg)
MFPatientsHealthyYesNot≥140/90<140/90
Total34291 to 61 (34.9±5.18)1944
Living28261 to 61 (32.2±4.75)104422321638
Dead6321 to 56 (40.00±8.89)9
Tab.1  Sociodemographic characteristics of the family members (Part 1/2)
Patients in generations
G OG AG BG CG DG E
GenderDAMDGenderDAMDGenderDAMDGenderDAMDMDMD
MFMFMFMF
Total1042100%1143.5±4.50100%4239.33±5.4466.67%2828.90±7.10*37.14%*00
Living1134.00±4.001732.00±5.10
Dead1042100%1143.5±4.50100%3142.00±5.501116.50±4.50
Tab.2  Table1 Sociodemographic characteristics of the family members (Part 2/2)
Fig.2  Cumulative survival function curve of the 19 patients with VHL disease. The median survival time after diagnosis was 4.896 years and the 10-year survival rate was 39.00%.
PatientsGenderDACAHBL(Cerebellar)Retinal angiomataPancreaticlesionsRenalPheochromocytomaParagangliomaManagementOutcome
PETsCystsRCCCystsHemi-Bilateral
O1M42#45SDUnknownDead
A1M39#40SDUnknownDead
A2F48#50SDSurgeryDead
B1M4552SDSurgeryDead
B7F34#36SDUnknownDead
B8M5051SDSurgeryDead
B9M39#42SDUnknownDead
C5M1223DDSurgeryDead
C21F21#21SDUnknownDead
B3M3856DDDDSurgeryAlive
B5F3045DDSurgeryAlive
C2F4141DDDDDDDDDDSurgeryAlive
C3F2437DDDDDDDDDDSurgeryAlive
C4F3434DDDDDDDDSurgeryAlive
C10F2828DDDDSurgeryAlive
C11M2424DDSurgeryAlive
C22F3542DDSurgeryAlive
C24F2932DDSurgeryAlive
C27F4142DDDDSurgeryAlive
Tab.3  Clinicopathological characteristics of the 19 patients with VHL disease from a large family in China
C2C3C4C11
Peripheral blood
RBC ( × 104 /μl)3.64.644.244.77
Hemoglobin (g/dl)110145132153
Platelet ( × 104 /μl)177335283163
WBC (/μl)64.25.46.2
Endocrinological test
ATI- Angiotensin-1 orthostatic6.854.713.212.62
AT1- Angiotensin-1 supine1.771.841.681.65
ATII- Angiotensin-2 orthostatic76.478.656.749.4
AT2- Angiotensin-2 supine54.243.253.452.4
Ald- Aldosterone orthostatic143.0139.8196.1180.0
ALD- Aldosterone supine108.8122.2108.9176.5
Urinalysis
VMA (mg/d)66.5349.158.5668.72
CA319.1432997.51212.76
17 KS71.01478.1667.361.2
17 OH4.420.5510.3620.31
NE122.58287.661.47147.24
E196.5640.436.0365.52
Tab.4  Biochemical parameters of the four patients with VHL disease manifesting pheochromocytoma.
Fig.3  Typical clinical imaging data of the patients affected with VHL disease. (A) Contrast-enhanced computerized tomography (CT) scan of patient C3 (a 37-year-old female) showing a mass lesion in the left adrenal, indicating pheochromocytoma (red arrow). (B) Contrast-enhanced CT scan of patient C2 (a 41-year-old female) showing masses in the right adrenal gland (red arrow) and pancreas (green arrow), indicating pheochromocytoma and PET, respectively. (C) Contrast-enhanced CT scan of patient C2 (a 41-year-old female) showing masses in the spleen (green arrow) and post-operation pathology of the resected specimens, confirming splenic metastasis of PETs. (D) Magnetic resonance imaging (T2W) of patient C4 (a 34-year-old female) showing lesions in the cerebellum, indicating hemangioblastoma (black arrow). (E) Contrast-enhanced CT scan of patient C11 (a 24-year-old male) showing a mass in the left adrenal, indicating pheochromocytoma (red arrow).
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