Phaeochromocytoma associated with a de novo VHL mutation as form fruste of von Hippel-Lindau disease.
Phaeochromocytomas usually occur sporadically but may be associated with dominant inherited cancer syndromes such as multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau disease (VHL) and type 1 neurofibromatosis. We report on a boy presenting at age 8 years with an isolated benign phaeochromocytoma of the left adrenal. Three years later a second adrenal phaeochromocytoma was diagnosed on the right side and removed. His family history was negative. Genetic analysis did not show a mutation in the MEN 2 susceptible proto-oncogene rearranged during transfection; however, we found a germline missense mutation in the VHL gene (nucleotide 695 G to A transversion) which has been described only twice before in the literature. Both parents had normal (wild type) VHL copies indicating that our patient had a de novo germline VHL mutation. Careful clinical evaluation of the patient at 18 years did not reveal any other manifestations of VHL disease.


CONCLUSIONS
Carriers of von Hippel-Lindau germline mutations can present with a form fruste of von Hippel-Lindau disease presenting initially with unilateral phaeochromocytoma and therefore mutation analysis should be carried out.
Frenzel
S
S
Division of Paediatric Endocrinology, University Hospital for Children and Adolescents, Loschgestrasse 15, 91054 Erlangen, Germany. HGDoerr@kinder.imed.uni-erlangen.de
Apel
T W
TW
Heidemann
P H
PH
Zerres
K
K
Neumann
H P
HP
Dörr
H G
HG
D000310:Adrenal Gland Neoplasms / Q000150:complications* / Q000235:genetics* / Q000601:surgery; D000315:Adrenalectomy; D002648:Child; D005500:Follow-Up Studies; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D010673:Pheochromocytoma / Q000150:complications* / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D000090063:Proto-Oncogene Mas; D018570:Risk Assessment; D014057:Tomography, X-Ray Computed; D006623:von Hippel-Lindau Disease / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*