Authors' objectives: Hereditary paraganglioma/pheochromocytoma (PGL/PCC) syndromes are a group of tumor predisposition syndromes characterized by the development of paragangliomas (PGLs) and pheochromocytomas (PCCs). PGLs are tumors of the paraganglia (groups of neuroendocrine cells located alongside the spinal column from the base of the skull to the pelvis) that may be located in the head and neck region, thoracic cavity, abdomen, or pelvic area. PCCs are PGLs located within the adrenal gland. The tumors associated with hereditary PGL/PCC syndromes, which may or may not secrete excess catecholamines (e.g., adrenaline and related metabolites), often develop before the age of 45 and sometimes as early as childhood. Clinical symptoms related to PGLs or PCCs are typically due to excess catecholamine secretion or mass effects related to tumor growth, such as increased blood pressure, headache, excess sweating, palpitations, and anxiety. Although the majority of tumors in affected individuals are benign, there is an elevated risk of malignancy in patients with hereditary PGL/PCC. Morbidity and mortality in affected individuals, however, is more frequently due to the complications related to tumor growth and excess catecholamine secretion. Episodes of significant hypertension can lead to changes in heart rhythm, heart attack, stroke, kidney failure, and potentially death. Hereditary PGL/PCC syndromes are most commonly caused by variants in genes encoding the subunits of the mitochondrial enzyme succinate dehydrogenase (SDH): SDHA, SDHB, SDHC, and SDHD. Variants in each of these genes have been found in patients with PGLs and/or PCCs, although SDHB and SDHD gene variants are the most common. PGL/PCC-related genes also include the SDH complex assembly factor 2 gene (SDHAF2), the MYC-associated factor X gene (MAX), and the transmembrane protein 127 gene (TMEM127). Variants in all 7 genes are inherited in an autosomal dominant manner (i.e., only 1 of a person's 2 copies of the gene needs to be altered in order to have the condition), with an affected individual having a 50% chance of passing on the disease-causing gene variant to each of his or her children. However, a parent-of-origin effect is seen with 3 of the PGL/PCC-associated genes: SDHD, SDHAF2, and MAX. Individuals who have inherited a SDHD, SDHAF2, or MAX gene variant from their father are at risk to develop PGLs or PCCs, while those who have inherited a similar change from their mothers will likely remain tumor-free. The treatment of tumors related to hereditary PGL/PCC syndromes typically includes surgical removal of the tumor and/or treatment with medications that block the excess catecholamines secreted by the tumor. There are currently no published guidelines regarding the management of at-risk carriers, although it is generally recommended that tumor surveillance begin at age 10 or at least 10 years before the earliest diagnosis in an affected family member. Surveillance typically includes lifelong biochemical screening for excess catecholamines, clinical evaluations, and imaging as necessary.

Project Status: Completed

Year Published: 2014

URL for published report: The report may be purchased from: http://www.hayesinc.com/hayes/crd/?crd=16708

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

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Contact Email: saleinfo@hayesinc.com

Copyright: 2014 Winifred S. Hayes, Inc