Genotype-Phenotype Correlations in Familial Pheochromocytomas
Issue: 3/2010
Author: А. Еlenkova, X. Jeunemaitre, AP Gimenez-Roqueplo, К. Hristozov, S. Zacharieva
Abstract:
Germline mutations in RET proto-oncogene, VHL gene and the genes encoding SDHB, SDHD and SDHC subunits of succinate dehydrogenase are responsible for approximately 30% of all pheochromocytomas. Most importantly, according to literature data, 12-24% of patients with an apparently sporadic pheochromocytoma (ASP) and a negative family history have a hereditary disease. The aim of this study was to identify carriers of genetic forms of pheochromocytoma (PCC) and catecholamine producing paragangliomas (PGL) and assess genotype-phenotype correlations in these patients.
Study design: Study participants were recruited from the PCC/PGL database comprising the electronic medical records from 106 patients being followed up at our centre. We investigated 20 patients who met the criteria for genetic analysis: 13 subjects with histologically confirmed pheochromocytomas, 1 family (father and his three children) with abdominal paragangliomas, 1 with a PGL of the urinary bladder, 1 patient with multiple paragangliomas and 1 woman with catecholamine-producing neuroblastoma. Direct DNA sequencing of five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) was performed using a twostep algorithm.
Results: Mutations in PCC/PGL susceptibility genes were found in 35% of investigated patients. The prevalence of familial forms by decades was as follows: 88% in 10-19 yr; 43% in 20-29 yr and 33% in 30-39 age at diagnosis. We have identified 5 families with von Hippel- Lindau disease and 1 family with a mutation in the gene encoding SDHD subunit. Mutation carriers were younger and more frequently had bilateral or extra-adrenal tumors.
Keywords: familial pheochromocytomas; paragangliomas; germline mutations; succinate dehydrogenase subunits; multiple endocrine neoplasia; von Hippel-Lindau disease; neurofibomatosis.
