Paraganglioma and pheochromocytomas are described as sporadic and hereditary conditions. Hereditary are the lesions in the tumor syndromes Multiple endocrine neoplasia type 2 (MEN 2), Von Hippel-Lindau disease (VHL), neurofibromatosis type 1 (NF1), and the paraganglioma syndromes type 1 type 3 and type 4 (PGL1, PGL3, PGL4). The susceptibility genes are for PGL1 SDHD, PGL3 SDHC, and for PGL4 SDHB. In contrast to PLG1 and PGL4 in which numerous carriers have been reported, PGL3 was described only in 4 index cases.
We established registries for head and neck paragangliomas (HNP) and pheochromocytomas and paragangliomas of other sites. After exclusion of NF1, MEN 2 and VHL we tested all subjects for SDHC, SDHB and SDHD germline mutations.
The Pheochromocytoma Registry comprised after exclusion of SDHB and SDHD mutations 369 subjects. None of these had an SDHC mutation. The HNP Registry comprised 121 subjects. Fife had an SDHC mutation. Thus, prevalence of of PGL 3 was 4%.
We were able to compare 22 SDHC positive subjects with 15 positive for SDHB and 42 positive for SDHB and 88 subjects with sporadic HNP (mutations of RET, VHL, SDHB, SDHC, SDHD excluded). Clinical features of SDHC mutation carriers were similar to sporadic HNP patients, but different to SDHB and SDHD carriers. Frequent location of HNP was the jugular ganglion. 4/5 patients had permanent palsy of at least one cranial nerve.
In the Freiburg HNP Registry, mutations were dominated by such of the SDHD gene followed by SDHB whereas SDHC mutations were the smallest group.
Moleculargenetic investigation of the SDHC gene should not be offered patients with pheochromocytoma. HNP patients who are negative for SDHD and SDHB mutations should be offered testing for SDHC mutations in order to detect HNP relapse and timely tumor diagnosis and treatment in relatives if shown to be carriers.
01 - 05 Apr 2006
European Society of Endocrinology