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SDH Mutations What you should know about SDH mutations Hereditary Paraganglioma/Pheochromocytoma syndrome (PGL/PCC) is a genetic condition caused by mutations in succinate dehydrogenase (SDH) genes. The four genes involved in PGL/PCC are SDHA (rare), SDHB, SDHC, and SDHD. These genes are responsible for suppressing tumor development. A change, or mutation, in one of these genes increases an individual’s risk for neuroendocrine tumors. The types of tumors are discussed below. The types of tumors associated with SDH mutations Paraglangiomas (PGL) are slow growing tumors that arise from paraganglia tissue • Parasympathetic PGL: typically located in the head or neck, usually nonfunctional (non-­‐secretory), 5% may hyper-­‐secrete hormones. PGLs can present with enlarging neck masses and no symptoms, difficulty swallowing, hoarseness, pain, cough, tinnitus (ringing in the ears) or hearing loss. • Sympathetic PGL: typically located in the thorax (chest cavity), abdomen, or pelvis; 90% are functionally active and secrete excess hormone (catecholamine). PGLs often present with high blood pressure and pulse, headaches, palpitations, excessive sweating, and anxiety due to the excess catecholamine. Pheochromocytomas (PCC) are PGLs located in the adrenal glands (on top of the kidneys). PCCs secrete catecholamines and present with symptoms of high blood pressure and pulse, headaches, palpitations, excessive sweating, and anxiety. Other features: gastrointestinal stromal tumors (GIST), kidney and thyroid cancers have been reported SDHB 77% develop tumors by age 50 Sympathetic PGL Higher chance for malignancy SDHC Rare – penetrance not reported Mostly Parasymathetic PGL Low risk for PCC Low change for malignancy Not multifocal SDHD 86% develop tumors by age 50 Parasympathetic PGL Potential for malignant Multifocal The risks to family members Mutations in the SDH genes are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a SDH mutation have a 50% chance of having the mutation. SDHD mutations only increase the risk for tumor development if inherited from the father. This is called paternal transmission. Managing the cancer risks Although there is no consensus regarding surveillance strategies for individuals with SDH mutations, it is reasonable to consider lifetime long annual biochemical and clinical surveillance which can guide imagining studies. Screening should begin at age 10 or 10 years before the earliest diagnosis in the family. Screening may include blood or urine analysis for hormones, CT or MRI scans, and physical exams to check for signs and symptoms of tumors. Management of tumors varies and might require surgical resection. Individuals with an SDH mutation should avoid cigarette smoking. 5323 Harry Hines Blvd.; Dallas, TX 75390-9161 * Phone: 214-645-2563 * Fax: 214-645-2562 * www.utsouthwestern.edu
Current as of 11/4/14