Horm Metab Res 2009; 41(9): 672-675
DOI: 10.1055/s-0029-1202814
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Rationalization of Genetic Testing in Patients with Apparently Sporadic Pheochromocytoma/Paraganglioma

A. Cascón 1 , 2 , E. López-Jiménez 1 , I. Landa 1 , S. Leskelä 1 , L. J. Leandro-García 1 , A. Maliszewska 1 , R. Letón 1 , L. de la Vega 1 , M. J. García-Barcina 3 , C. Sanabria 4 , C. Álvarez-Escolá 5 , C. Rodríguez-Antona 1 , 2 , M. Robledo 1 , 2
  • 1Spanish National Cancer Research Centre (CNIO), Hereditary Endocrine Cancer Group,Madrid, Spain
  • 2Genotyping Unit, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  • 3Genetics Department, Hospital de Basurto, Bilbao, Spain
  • 4Department of Endocrinology and Nutrition, Hospital Clínico San Carlos, Madrid, Spain
  • 5Endocrinology Service, Hospital La Paz, Madrid, Spain
Further Information

Publication History

received 16.12.2008

accepted 27.01.2009

Publication Date:
02 April 2009 (online)


Hereditary susceptibility to pheochromocytoma (PCC) and paraganglioma (PGL) represents a very complex genetic scenario. It has been reported that the absence of familial antecedents of the disease does not preclude the existence of a mutation affecting any of the five major susceptibility genes. In fact, 11–24% of apparently sporadic cases (without familial or syndromic antecedents) harbor an unexpected germline mutation, but we do not know what is happening in “truly apparently” sporadic patients (i.e., apparently sporadic cases diagnosed with only one tumor). In the present study, we have analyzed 135 apparently sporadic patients developing a single tumor for the five major susceptibility genes: VHL, RET, SDHB, SDHC, and SDHD. Fourteen percent of cases were found to harbor a germline mutation, and only 2.2% of patients were older than 45 years at onset. By taking into account the tumor location and a threshold age at onset of 45 years, we propose a rational scheme for genetic testing. Analyzing VHL and RET genes would be recommended only in young patients developing a single PCC. On the other hand, genetic testing of SDHD should be done in all patients developing an extra-adrenal tumor before the age of 45, and SDHC could be the responsible gene in cases developing a single head and neck tumor, independently of age. Finally, the analysis of SDHB should always be performed because of its association to malignancy and the low penetrance of mutations affecting this gene.



M. Robledo, PhD 

Hereditary Endocrine Cancer Group

Human Cancer Genetics Programme

Centro Nacional de Investigaciones Oncológicas

Melchor Fernández Almagro 3

28029 Madrid


Phone: +34/91/224 69 47

Fax: +34/91/224 69 23

Email: [email protected]