Hereditary Paraganglioma Pheochromocytoma syndrome and the SDH genes

Hereditary Paraganglioma Pheochromocytoma syndrome is associated with mutations in the SDH family of genes (SHDA, SDHB, SDHC, SDHD and SDHAF2 ). It is characterised by the development of paraganglioma and/or pheochromocytoma (“pheos” for short). In some cases, stomach cancers (called GISTs or GastroIntestinal Stromal Tumours) and/or kidney cancers occur. The likelihood of these tumours and cancers developing depends on which of the SDH genes is affected. It is very rare, affecting 1 in a million people. Paraganglioma and pheos can be associated with other syndromes including
  • Von Hippel Lindau syndrome (VHL gene)
  • Multiple Neuroendocrine syndrome (RET gene)
  • Neurofibromatosis type 1 (NF1 gene)
Paraganglioma and pheos are very rare tumours. However, when they occur, there is a 10% to 30% chance that they occurred because of a germline (inheritable) gene mutation. Genetic testing is nearly always recommended. Often the clinical or family history and/or staining tests of the tumour gives a clue as to which gene may be involved. If not, a pheo gene panel test to check the 10 or more pheo genes may be recommended. Paraganglioma arise from tissue that is part of the nervous system and that runs along the outside of the spine. This tissue is called the sympathetic and parasympathetic nervous system. Pheos are tumours found in the adrenal gland above the kidney. The tumours may grow and press on other structures. Sometimes they may become cancerous and spread. Pheos and paraganglioma that arise in the sympathetic nervous system usually secrete hormones, especially if located in the chest, abdomen and pelvis. These hormones are involved in the “flight or fight response”. They are called catecholamines and include hormones such as adrenalin. The symptoms of intermittent catecholamine excess include episodes of heart palpitations associated with high blood pressure, facial flushing, headaches and sweating. There is a 50% chance of a person who carries a germline SDH mutation, whether male or female, passing the mutation to their son or daughter. If a mutation were identified, then predictive testing would be available for adult blood relatives. This allows screening of at risk relatives to start early. The SDHD gene is unusual: the mutation almost never causes problems if it is inherited from the mother (this is called imprinting). There is lot’s that can be done to reduce risk. Individuals with an SDHB, SDHC or SDHD gene mutation should start screening from ages 5 to 10, depending on the mutation type. (The SDHA gene mutations are less likely to cause problems). This allows early detection and treatment of tumours. Screening includes annual blood pressure measurements and fasting blood tests as well as imaging of the spine, kidneys and adrenals every 2 to 3 years. The SDH genes are involved in pathways that are switched on when oxygen levels are low. People with SDH and other paraganglioma and pheo gene mutations should not smoke or live at high altitudes. For more information, see the links below:
  • Genetics Home Reference site has information on Hereditary Paraganglioma Pheochromocytoma syndrome
  • The Cancer Institute's eviQ pages provide accurate management and testing guidelines for individuals with Hereditary Paraganglioma Pheochromocytoma syndrome. The site is open to patients and doctors: they just ask that you register so that can track usage. Go to www.eviQ.org.au and look under Cancer Genetics, Management in the left hand Category Menu
  • The Pheo Para Trooperssupport group is for individuals and families affected by Hereditary Paraganglioma Pheochromocytoma syndrome, Paraganglioma and/or Pheochromocytoma. They are based in the USA but have members around the world.