Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 1857 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 

Table of Contents   
CASE REPORT  
Year : 2015  |  Volume : 26  |  Issue : 6  |  Page : 1266-1269
Dizziness and renal failure revealing the Von Hippel Lindau disease


1 Department of Nephrology, CHU Hassan II, Fez, Morocco
2 Department of Radiology, University Hospital Hassan II, Fez, Morocco

Click here for correspondence address and email

Date of Web Publication30-Oct-2015
 

   Abstract 

The germinal mutation of the Von Hippel Lindeau (VHL) tumor suppressor gene predisposes to the development of benign or malignant richly vascularized tumors. VHL disease is an autosomal-dominant disorder with complete penetrance at the age of 60 years. Screening for people at risk is strongly recommended, and careful monitoring allows treatment of the tumor lesions as early as possible. A 42-year-old man sought medical consult for hematuria, disabling dizziness and balance disorders lasting for two months. The neurological examination revealed the presence of a kinetic cerebellar syndrome. The cerebro-spinal magnetic resonance imaging revealed multiple hemangioblastomas, both encephalic and medullar. Abdominal computed tomography revealed a big solid mass in the left kidney and multiple intra-parenchymal cystic lesions in the right kidney and the pancreas. The diagnosis of VHL disease was strongly suspected. The operative indication of brain damage and renal mass have been submitted. The pathological study of the renal surgical specimen revealed a clear cell carcinoma. The post-operative course was uneventful and all the symptoms have disappeared. Genetic study and close follow-up are recommended for this disease.

How to cite this article:
Sekkouri KA, Alaoui S R, Batta F, Belghiti K A, Alaoui H, El Fadil C, Arrayhani, Husseini T S. Dizziness and renal failure revealing the Von Hippel Lindau disease. Saudi J Kidney Dis Transpl 2015;26:1266-9

How to cite this URL:
Sekkouri KA, Alaoui S R, Batta F, Belghiti K A, Alaoui H, El Fadil C, Arrayhani, Husseini T S. Dizziness and renal failure revealing the Von Hippel Lindau disease. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2020 May 29];26:1266-9. Available from: http://www.sjkdt.org/text.asp?2015/26/6/1266/168667

   Introduction Top


The Von Hippel Lindeau (VHL) gene plays a fundamental role in the tissue response to hypoxia. [1] A germinal mutation of the VHL tumor suppressor gene predisposes to the development of benign or malignant tumors that are richly vascularized in the central nervous system, retina, kidneys, adrenals and pancreas. [2] VHL disease is an autosomal-dominant inherited disorder with complete penetrance at the age of 60 years. [2] Its incidence is estimated at a new case for 36,000 births. [2],[3] Clinical manifestations usually appear between 18 and 30 years. [1] The diagnosis is genetic. The treatment of the majority of tumor lesions is surgical. [4],[5],[6] Screening for people at risk is strongly recommended; also, careful monitoring allows the treatment of the tumor lesions as early as possible. [7]

Here, we describe a patient with multiple tumors related to the VHL disease with surgical management to his tumors in the neurological system and kidneys.


   Case Report Top


A 42-year-old man born from a non-consanguineous marriage and who had no children sought medical advice for hematuria, disabling dizziness and balance disorders lasting for two months. The patient had no family history of VHL.

The neurological examination revealed the presence of a kinetic cerebellar syndrome, dysarthria, discrete central facial paralysis and signs of pyramidal irritation. Examination of the fundus was unremarkable.

The laboratory investigations revealed proteinuria at 1.2 g/day. The measurement of urinary catecholamines and methoxy derivatives disclosed normal levels.

Cerebro-spinal magnetic resonance imaging was performed objectifying multiple hemangioblastomas, both encephalic and spinal, and the largest one was in the right cerebellar tonsil [Figure 1] and [Figure 2]. There was no individualized endolymphatic sac tumor.
Figure 1: MRI revealing the enormous cerebellar hemangioblastoma with tonsillar involvement (sagittal section).

Click here to view
Figure 2: MRI showing cerebellar hemangioblastoma with the enormous commitment amygdala (coronal).

Click here to view


Abdominal computed tomography revealed a big solid mass in the left kidney, long axis of 5 cm, at the upper pole, and very limited, with no signs of tampering or capsular invasion pedicle. Multiple intra-parenchymal cystic lesions were also found in the right kidney and pancreas without detectable adrenal masses.

The diagnosis of VHL disease was strongly suspected. Only the large cerebellar hemangioblastoma was removed without an opportunity to the others.

The patient was subsequently nephrectomized. The pathological study of the surgical specimen revealed clear cell carcinoma.

The post-operative course was uneventful and all the neurological and urinary symptoms disappeared. The genetic investigations could not be performed due to the lack of resources available to the patient and his family.


   Discussion Top


The inactivation of this gene plays a crucial role in angiogenesis, suppressing the expression of the transcription factor, hypoxia-inducible factor (HIF), which is involved in cell growth. [8]

There is usually a demonstrative family history; however, the "cryptic" forms due to neomutations are estimated at 20%. [4]

VHL disease affects many organs, but the attacks are not synchronous and will occur sequentially in life. [9],[10],[11],[12] It appears clinically in six major lesions: The central nervous system hemangioblastoma, hemangioblastoma of the retina, clear cell renal carcinoma and renal cysts, neuro-endocrine tumors or pancreatic cysts, pheochromocytomas and endo-lymphatic sac tumor. The frequency and age of revelation of these manifestations are variable [Table 1]. [8],[10]
Table 1: Frequency and age of revelation manifestations of VHL.

Click here to view


The diagnosis is established in the presence of two major lesions, including a hemangioblastoma in the absence of family history or a single lesion in the presence of family history. There are two main clinical VHL types: (1) classical VHL type I without pheochromocytoma and (2) VHL type II with pheochromocytoma. [11],[12]

In one family, there is also a phenotypic heterogeneity: Some patients can have a severe form with multiple tumors, requiring repeated interventions, while others have only a small number of lesions without a clinical impact.

The age of discovery of the disease for our patient was advanced compared with the usual cases, explaining the multi-visceral lesions. There was no family or at least no known history of VHL. Three major lesions were found: Hemangioblatomas of the central nervous system, renal clear cell cancer and pancreatic cysts. Accordingly, the diagnosis of VHL disease was evident.

The final diagnosis, however, involves a genetic detection of the germinal mutation of the VHL gene, which is a tumor suppressor gene located on chromosome 3. This gene is small (exon 3), which allows a reliable genetic diagnosis (almost 100% detection). [11],[12]

Genetic study and research of the VHL gene mutation appears essential to carry the positive diagnosis and also for pre-symptomatic screening for people at risk of family members. [9],[10],[11],[12]

This could not be performed in our case due to the lack of resources available to our patients and their families.

At the therapeutic level, the CNS tumors require neurosurgical intervention. The multiple natures of the tumors and the possible unresectable locations explain that these tumors remain a major cause of death. Stereo-tactic radiosurgery has recently emerged as a possible alternative to surgery that would control the majority of <3 cm hemangioblastomas. [4],[9] The treatment of renal cell carcinoma is the most difficult because of the frequent multiplicity of tumors, requiring repeated interventions. [1],[8] Whenever feasible, conservative surgery is recommended and solid tumors are removed if ≥ 3 cm in diameter and to try to conserve as much kidney tissue as possible. [1],[6] A new therapeutic technique, the radiofrequency, has recently been introduced, and it allows "grilling" the most superficial tumors <3 cm with a satisfactory oncological safety. [1],[12]

Pancreatic cysts do not justify any surgery, but percutaneous drainage or the establishment of a biliary stent is indicated if there is a mechanical compression. Our patient did not need any intervention on the encountered pancreatic tumors.

Renal tumor in our patient exceeded 5 cm in diameter and it required a total nephrectomy of the left kidney. Most brain and spinal hemangioblastomas were not extractable, only the largest was removed.

In conclusion, most of the manifestations of VHL disease are potentially treatable. Thereby, genetic testing should be practiced for the identification of the pre-symptomatic patients. New therapies are promising, including molecules opposing the function of the HIF factor or possibly gene therapy to restore the function of the VHL gene.

 
   References Top

1.
Chrétien Y, Chauveau D, Richard S, et al. Treatment of von Hippel-Lindau disease with renal involvement. Prog Urol 1997;7:939-47.  Back to cited text no. 1
    
2.
Maher ER, Yates JR. Familial renal cell carcinoma: Clinical and molecular genetic aspects. Br J Cancer 1991;63:176-9.  Back to cited text no. 2
    
3.
Richard S, Olshwang S, Chauveau D. The von Hippel Lindau. Med Sci 1995;11:45-51.  Back to cited text no. 3
    
4.
Chang SD, Meisel JA, Hancock SL, Martin DP, McManus M, Adler JR Jr. Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery. Neurosurgery 1998;43:28-34.  Back to cited text no. 4
    
5.
Giraud S, Plauchu H, Dollfus H. The von Hippel Lindau. Sheet recommendations of the French society of human genetics. The specifications of genetic diagnosis. INSERM; 2001.  Back to cited text no. 5
    
6.
Herring JC, Enquist EG, Chernoff A, Linehan WM, Choyke PL, Walther MM. Parenchymal sparing surgery in patients with hereditary renal cell carcinoma: 10-year experience. J Urol 2001;165:777-81.  Back to cited text no. 6
    
7.
Kaelin WG Jr. Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2002;2:673-82.  Back to cited text no. 7
    
8.
Lonser RR, Glenn GM, Walther M, et al. von Hippel-Lindau disease. Lancet 2003;361:2059-67.  Back to cited text no. 8
    
9.
Niemelä M, Lim YJ, Söderman M, Jääskeläinen J, Lindquist C. Gamma knife radiosurgery in 11 hemangioblastomas. J Neurosurg 1996;85:591-6.  Back to cited text no. 9
    
10.
Richard S, David PH, Marsot Dupuch K. Central nervous system hemangioblastomas, Endolymphatic sac tumors and von Hippel Lindau disease. Neurosurg Rev 2000;23:1-22.  Back to cited text no. 10
    
11.
Richard S; French VHL Study Group. von Hippel-Lindau disease: Recent advances and therapeutic perspectives. Expert Rev Anticancer Ther 2003;3:215-33.  Back to cited text no. 11
    
12.
Richard S. The Von Hippel Lindau. Orphanet Encyclopedia; February, 2002.  Back to cited text no. 12
    

Top
Correspondence Address:
Kawtar Alaoui Sekkouri
Department of Nephrology, CHU Hassan II, Fez
Morocco
Login to access the Email id


DOI: 10.4103/1319-2442.168667

PMID: 26586070

Rights and Permissions


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]



 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
   Case Report
   Discussion
    References
    Article Figures
    Article Tables
 

 Article Access Statistics
    Viewed1592    
    Printed15    
    Emailed0    
    PDF Downloaded261    
    Comments [Add]    

Recommend this journal