Hereditary Paraganglioma-Pheochromocytoma (PGL-PCC) Syndrome is characterized by the presence of paragangliomas (PGLs), most often on the head and neck.  There are two subtypes of PGLs, sympathetic and parasympathetic paragangliomas. Sympathetic PGLs (sPGLs) are associated with the sympathetic nervous system and most commonly originate from chromaffin cells.  sPGLs are composed of pheochromocytomas (PCC, fPGLs, PH, or PHEOs) and extra-adrenal PGLs, and are characterized by the tumor production and secretion of catecholamines arising from the adrenal medulla (pheochromocytoma) or sympathetic nervous ganglia.  Parasympathetic PGLs typically do not secrete catecholamines and arise from chief cells. Estimated prevalence of PHEOs is 1:4500 and 1:1700 for PGLs, with an annual incidence of 3 to 8 cases per 1 million a year in the general population. The age of onset for PGL individuals is between 15 and 45 years of age, with early symptoms typically consisting of local swelling and cranial nerve injury. Although the tumors are benign in nature, only 4-16% shows malignant degeneration, giving rise to swelling causing cranial nerve damage, facial asymmetry, deafness, or hoarseness. When catecholamines are released in excess they may cause sudden adverse symptoms such as headache, heart palpitations, increased blood pressure, episodic sweating, pallor, and anxiety, all of which may appear and leave sporadically.  Diagnosis for PGLs is determined by a biochemical assay, tumor location, function, inheritance, and gene mutation. If the tumor has metastasized the overall five year survival rate in patients is 40-72%.  Size and location of the primary tumor has been correlated with risk for metastasis and the duration of survival.

Germline mutations in three of the succinate dehydrogenase (SDH, mitochondrial complex II) subunits (SDHD, SDHB and SDHC) cause susceptibility to head and neck paragangliomas, and may be found in approximately 30% of unselected patients.  Germline SDHB, SDHC, SDHD, SDHAF2, MAX and TMEM127 mutations may cause head and neck paragangliomas and pheochromocytoma susceptibility.  To note, RET, VHL and NF1 mutations have also been found to be part of the hereditary paraganglioma-pheochromocytoma spectrum.