SDHB-associated hereditary paraganglioma and pheochromocytoma
What Does It Mean to Test Positive for an SDHB Mutation?
Individuals who test positive for a mutation in the SDHB gene have an increased chance of developing tumors of the nervous and endocrine systems, also sometimes called neuroendocrine tumors.
What Are the Cancer Risks Associated with an SDHB Mutation?
SDHB is a gene associated with hereditary paraganglioma and pheochromocytoma.
A paraganglioma is a rare, usually benign, tumor that occurs in structures associated with nerve cells. These tumors most frequently develop in the head, neck, or torso.
A pheochromocytoma is a rare, usually benign, tumor located on the adrenal glands (hormone-producing structures above the kidneys) that impacts the levels of certain hormones in the body.
SDHB mutations are associated with cancer risks ranging from 34 to 97%, amongst individuals with hereditary paraganglioma and pheochromocytoma. Cancer types include a type of digestive cancer known as GIST (gastrointestinal stromal tumors), thyroid cancer, brain tumors (neuroblastoma), and kidney cancer (renal cell carcinoma). The average age of the first cancer diagnosis is 30 years of age. However, cancer can occur in both children and older adults (age 6 to 77 years).
What Cancer-Screening or Risk-Reducing Options Are Available?
Symptoms and complications are often managed by medication. Surgical removal of tumors is recommended, due to the high chance for a tumor to become cancerous. Current recommendations call for lifelong screening beginning at age 10, or at least 10 years before the earliest age of diagnosis in a family. Screening includes biochemical and clinical monitoring through blood tests and physical examinations. Imaging studies such as MRI or CT may also be used to screen for tumors in individuals with SDHB mutations, and screening for kidney (renal cell) cancer should be considered. An evaluation with a genetics specialist is recommended for SDHB mutation carriers.
What Is the Chance That Family Members of SDHB Mutation Carriers Have the Same Mutation?
SDHB mutations are passed down in a family. This means that family members of SDHB mutation carriers may have the same mutation and may also be at an increased risk of developing complications associated with paragangliomas and pheochromocytomas. In other instances, a sporadic genetic mutation occurs in a single family member, which means that an individual could be the first person in a family to have an SDHB mutation. In either case, it is important for SDHB mutation carriers to discuss genetic test results with family members.
- Close blood relatives of SDHB mutation carriers, such as parents, siblings, and children, have up to a 50% chance of having the same mutation.
- For individuals who are determined to be the first affected member of a family, which has been reported to occur in a small percentage of individuals, testing is still indicated for biological children, who have a 50% chance of inheriting the SDHB mutation.
- Distant relatives, such as aunts, uncles, grandparents, and cousins, may also have a chance of having the same SDHB mutation.
- A physician or a genetic counselor can help mutation carriers decide which side of the family (the mother's or the father's) the mutation is more likely to be on. In general, the mutation will only be inherited from one side of the family and is more likely to be inherited from the side of the family that has a history of paraganglioma or pheochromocytoma.
Genetic testing of family members can help determine which family members are at increased risk for the development of neuroendocrine tumors and may benefit from the screening and/or risk-reduction options discussed above. Family members who test negative for a known familial SDHB mutation likely have the same risk for cancer as the general population and can follow the general population's screening guidelines.
What Else Should SDHB Mutation Carriers Know?
Mutation carriers who are interested in options to prevent passing their mutation to future children may wish to consider preimplantation genetic diagnosis (PGD). PGD is a procedure that involves in vitro fertilization (IVF) and can determine if an embryo carries the genetic mutation present in a family. Determining which embryos carry a family mutation may allow a mutation carrier to prevent the condition from being passed to future children. The decision to undergo PGD is personal. Mutation carriers and their family members can talk with a healthcare provider to learn more about their reproductive options.