Genetic testing in pheochromocytoma or functional paraganglioma.
OBJECTIVE
To assess the yield and the clinical value of systematic screening of susceptibility genes for patients with pheochromocytoma (pheo) or functional paraganglioma (pgl).


METHODS
We studied 314 patients with a pheo or a functional pgl, including 56 patients having a family history and/or a syndromic presentation and 258 patients having an apparently sporadic presentation. Clinical data and blood samples were collected, and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened. Neurofibromatosis type 1 was diagnosed from phenotypic criteria.


RESULTS
We have identified 86 patients (27.4%) with a hereditary tumor. Among the 56 patients with a family/syndromic presentation, 13 have had neurofibromatosis type 1, and germline mutations on the VHL, RET, SDHD, and SDHB genes were present in 16, 15, nine, and three patients, respectively. Among the 258 patients with an apparently sporadic presentation, 30 (11.6%) had a germline mutation (18 patients on SDHB, nine patients on VHL, two patients on SDHD, and one patient on RET). Mutation carriers were younger and more frequently had bilateral or extra-adrenal tumors. In patients with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant.


CONCLUSIONS
Genetic testing oriented by family/sporadic presentation should be proposed to all patients with pheo or functional pgl. We suggest an algorithm that would allow the confirmation of suspected inherited disease as well as the diagnosis of unexpected inherited disease.
Amar
Laurence
L
Université Paris-Descartes, Faculté de Médecine, France.
Bertherat
Jérôme
J
Baudin
Eric
E
Ajzenberg
Christiane
C
Bressac-de Paillerets
Brigitte
B
Chabre
Olivier
O
Chamontin
Bernard
B
Delemer
Brigitte
B
Giraud
Sophie
S
Murat
Arnaud
A
Niccoli-Sire
Patricia
P
Richard
Stéphane
S
Rohmer
Vincent
V
Sadoul
Jean-Louis
JL
Strompf
Laurence
L
Schlumberger
Martin
M
Bertagna
Xavier
X
Plouin
Pierre-François
PF
Jeunemaitre
Xavier
X
Gimenez-Roqueplo
Anne-Paule
AP
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002648:Child; D005260:Female; D005602:France; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000175:diagnosis / Q000235:genetics; D010235:Paraganglioma / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D010673:Pheochromocytoma / Q000175:diagnosis / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics; 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; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C497446:VHL protein, human