Review: Should patients with apparently sporadic pheochromocytomas or paragangliomas be screened for hereditary syndromes?
BACKGROUND
The recent identification of germline mutations of the mitochondrial complex II genes in variants of paraganglioma/pheochromocytoma syndrome has enlarged the number of known causative genes for hereditary pheochromocytoma. A question confronting clinicians is whether they should screen patients with apparently sporadic pheochromocytomas for unsuspected germline mutations of some or all of the seven genes known to cause hereditary paraganglioma or pheochromocytoma (NF1, VHL, RET, MEN1, SDHD, SDHC, and SDHB). A positive answer was suggested by a report that placed the estimate of hereditary disease in apparently sporadic pheochromocytoma as high as 24%.


METHODS
We applied clinically useful criteria to a review of the literature, defining cases of apparently sporadic pheochromocytoma as those without a suspicious personal or family history, with a focal, unilateral pheochromocytoma, and presenting at age less than 50 yr.


RESULTS
We reduced the overall estimate of unsuspected hereditary pheochromocytoma patients with apparently sporadic pheochromocytoma to approximately 17%. Mutations in only three genes (VHL, SDHB, and SDHD) accounted for almost this entire minority, and unsuspected RET mutation was rare. Costs, coverage by insurance, the potential effect on insurability, and deficient information for populations outside of referral centers should be considered before recommending genetic testing in patients with apparently sporadic presentations of pheochromocytomas.


CONCLUSIONS
We recommend genetic testing for patients with an apparently sporadic pheochromocytoma under the age of 20 yr with family history or features suggestive of hereditary pheochromocytoma or for patients with sympathetic paragangliomas. For individuals who do not meet these criteria, genetic testing is optional.
Jiménez
Camilo
C
Instituto Nacional de Cancerología, Fundación Santafé de Bogotá, Colombia, South America.
Cote
Gilbert
G
Arnold
Andrew
A
Gagel
Robert F
RF
D000328:Adult; D018095:Germ-Line Mutation; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D010235:Paraganglioma / Q000175:diagnosis / Q000235:genetics*; D010673:Pheochromocytoma / Q000175:diagnosis / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics; D013577:Syndrome; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
D007506:Iron-Sulfur Proteins; D008565:Membrane Proteins; D021122:Protein Subunits; C491545:SDHD protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human