An update on the genetics of pheochromocytoma

Abstract

Phaeochromocytomas and paragangliomas are rare tumors. Nowadays, about 30% or more of them are thought to be of inherited origin due to germ-line mutations in at least ten genes. There is data linking specific genotypes of these tumors to specific locations, typical biochemical phenotypes or future clinical behaviors. Conversely, clinical features, catecholamine production and histological evaluation can help with the proper order of genetic testing for phaeochromocytoma and paraganglioma. The identification of a germ-line mutation can lead to an early diagnosis, appropriate treatment, regular surveillance and better prognosis not only for the patient, but also for their family members. Moreover, the latest discoveries in molecular pathogenesis will probably provide a basis for future personalized therapy.

The clinical genetics of phaeochromocytoma and paraganglioma

“…In VHL syndrome, catecholamine-secreting tumours develop in 10-20% with a mean age of presentation of 30 years (25). They are more frequently benign, intraadrenal and bilateral.…”

“…head and neck paraganglioma), multifocal, recurrent or malignant disease and a positive family history of phaeochromocytoma. Therefore, patients with these features were considered for genetic testing (25,53). Then, depending on certain feature associated with different mutations one could decide on the order of genes to be tested (Figure 1).…”

Pheochromocytomas

“…As with MEN 2, von Hippel Lindau (VHL) and neuroibromatosis type 1 (NF1) are characterized by a predisposition to multiple tumor types. The rate of pheochromocytoma development in NF1 is signiicantly lower than in VHL or MEN 2 syndromes; however, the metastatic rate for NF1-associated pheochromocytomas of approximately 12% is higher than with MEN 2 or VHL [21]. The Carney Syndrome (or Carney Complex) is a triad of tumors, which includes the development of paragangliomas.…”

Rare Cause of Severe Hypertension in a Young Woman

“…10,11 Hereditary paragangliomas are most often associated with mutations in genes encoding or stabilizing the SDH enzyme complex (SDHB, SDHD, SDHC, and SDHA), which forms the mitochondrial complex 2 and links the Krebs cycle to electron transport, 12 whereas mutations in other genes that have been identified as predisposing to pheochromocytoma and paraganglioma include SDHAF2, MAX, and TMEM127. 13 Overall, the risk of malignancy, defined as the presence of metastases in nonchromaffin tissue, is relatively low, with prevalence between 10% and 17%.…”