Hereditary Pheochromocytoma and Paraganglioma Panel

Paragangliomas are rare, adult-onset neuroendocrine tumors that arise from paraganglia and may or may not be malignant. Paraganglia are a collection of neuroendocrine tissues that are distributed throughout the body, from the middle ear and the skull base (called head and neck paragangliomas or HNP) to the pelvis. Paragangliomas located outside the head and neck most commonly occur in the adrenal glands and are called pheochromocytomas (PCC). PCC can cause excessive production of adrenal hormones, which can result in hypertension, headaches, anxiety, tachycardia, anxiety, and sweaty or clammy skin. PGL and PCC are rare and most cases are sporadic, but approximately one-third are familial and due to an identifiable pathogenic variant in a disease-causing gene. Familial PGL/PCC can be non-syndromic or a feature of an underlying condition such as neurofibromatosis type 1, von Hippel-Lindau syndrome, or multiple endocrine neoplasia type 2. Paragangliomas are also a feature of Carney-Stratakis syndrome, an autosomal dominant condition characterized by the development of paragangliomas and/or gastrointestinal stromal tumors (GIST). Most cases are caused by pathogenic variants in three genes, SDHD, SDHC, and SDHB, which are known by their syndromic names PGL1, PGL3, and PGL4, respectively. Pathogenic variants in MAX, SDHD and SDHAF2 demonstrate parent-of-origin effects and generally cause disease only when inherited from the father. Other genes that are causative for Hereditary Paraganglioma-Pheochromocytoma syndrome include TEME127, FH, NF1, VHL, RET, and MEN1. This test is specifically designed to detect germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue. The panel includes sequence and deletion/duplication analysis of all the listed genes.