Head and Neck Paragangliomas in Von Hippel-Lindau Disease and ...

one case with HNP and adrenal pheochromocytoma, lung metastases were found by biopsy (20). Most
patients were diagnosed with HNP in their 3 rd to 5 th decades of life. Of note, 3 of the 16 VHL cases, 1
from France, 1 from Germany and 1 from America (23) share the identical mutation VHL p.Tyr98His
which has been shown as a founder effect in the Blackforest with emigrants to Pennsylvania and Ohio
(28).
In summary, VHL is the dominant syndrome in Non-SDHx mutation-associated inherited HNP. Since
the majority of our and the reported patients with HNP have clinical features suggesting VHL, MEN 2
or NF 1, our data provide evidence that genetic testing for VHL, RET and NF1 mutations are not
necessary unless other syndromic component tumors occur in the patient or there is at least one family
member with known VHL, MEN 2 or NF 1. If the data continue to hold, then NF 1 needs not to be
considered in HNP presentations. In pursuing this exercise, it also became obvious that there exists
an additional set of individuals who have at least one “red flag” likewise multiple HNPs, additional
pheochromocytoma and/or a family history for paraganglial tumors denoting genetic contribution but
are without any mutation in the known PGL/pheochromocytoma-predisposing genes. These will serve
to guide the search for novel predisposition genes.
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