Genetics and Hereditary Cancers

Hereditary Paraganglioma-Pheochromocytoma Syndrome

Appointment New Patient Appointment or 214-645-2563

Appointment New Patient Appointment or 214-645-2563

What You Should Know About Hereditary Paraganglioma-Pheochromocytoma Syndrome

Individuals with hereditary paraganglioma-pheochromocytoma syndrome have an increased risk for developing neuroendocrine tumors called paragangliomas (PGLs) and pheochromocytomas (PCCs). While many of these tumors are not cancerous, there is a risk for malignant transformation or other complications such as high blood pressure or stroke, so early detection is important.

Hereditary paraganglioma-pheochromocytoma syndrome is caused by pathogenic/likely pathogenic variants in the MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, and TMEM127 genes.

While paragangliomas and pheochromocytomas are rare tumors, UT Southwestern has one of the largest populations of patients with these tumors, and we are experienced in providing care for people with this hereditary syndrome.

UT Southwestern’s Genetic Cancer Prevention Clinic (GCPC) can help ensure people are receiving appropriate cancer surveillance and management based on their genetic testing results. For more information about the GCPC or to request an appointment, please call us at 214-645-2563.

  1. SDHA
  2. SDHAF2A
  3. SDHB
  4. SDHC
  5. SDHD
surgical gastrointestinal cancer

SDHA

Cancer Risks Associated with a Pathogenic/Likely Pathogenic Variant in SDHA

Pathogenic/likely pathogenic (P/LP) variants in the SDHA gene are a rare cause of neuroendocrine tumors called paragangliomas (PGLs) and pheochromocytomas(PCCs), accounting for about 3% of cases. The chance for a person with an SDHA P/LP variant to develop a PGL or PCC by age 70 is currently thought to be up to 10-13%. With the variants, there might also be an increased risk for the development of other types of tumors or cancer, such as gastrointestinal stromal tumors, kidney cancer, pituitary adenomas, and papillary thyroid cancer. Given the rarity of SDHA P/LP variants, information about the true number of individuals with SDHA P/LP variants and rates of cancer is still limited.

Managing Cancer Risks

PGLs and PCCs

Additional screenings/risk management or earlier ages of screenings/risk management may be considered based on personal risk factors and family history.

Risks to Family Members

P/LP variants in the SDHA gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an SDHA P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial SDHA P/LP variant, and both males and females can pass it on to their children.

Pituitary Adenoma scan

SDHAF2

Cancer Risks Associated with a Pathogenic/Likely Pathogenic Variant in SDHAF2

Pathogenic/likely pathogenic (P/LP) variants in the SDHAF2 gene are a rare cause of hereditary neuroendocrine tumors called paragangliomas (PGLs) and pheochromocytomas (PCCs). To date, PGLs and PCCs have been found in individuals with SDHAF2 P/LP variants, but the lifetime risks for tumors associated with this gene are not currently known. So far, SDHAF2 P/LP variants have shown a parent-of-origin effect, meaning that only individuals who inherit the variant from their father appear to have an increased risk of developing the tumors.

Managing Cancer Risks

PGLs and PCCs

  • Endocrinology specialists work with patients to determine appropriate risk management for hereditary endocrine tumors.
  • Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
    • Blood pressure monitoring
    • Blood work and urine analysis to monitor metanephrine levels
    • MRI or CT (whole-body and/or sectioned imaging)

Additional screenings/risk management or earlier ages of screenings/risk management may be considered based on personal risk factors and family history.

Risks to Family Members

P/LP variants in the SDHAF2 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a SDHAF2 P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial SDHAF2 P/LP variant, and both males and females can pass it on to their children. SDHAF2 P/LP variants appear to demonstrate a parent-of-origin effect.

parents and children

SDHB

Cancer Risks Associated with a Pathogenic/Likely Pathogenic Variant in SDHB

The risk of developing neuroendocrine tumors called paragangliomas (PGLs) and pheochromocytoms (PCCs) in individuals with pathogenic/likely pathogenic (P/LP) variants in the SDHB gene has been estimated to be 20-80%. More recent research has estimated the risk at 20-40%, but the overall risk for developing PGLs or PCCs may depend on the number of family members with these tumors. While PGLs and PCCs are typically benign tumors, there is thought to be a higher risk of cancerous tumors with SDHB P/LP variants compared to other hereditary PGL and PCC syndromes. With the variants, there might also be an increased risk for other types of tumors or cancer, such as gastrointestinal stromal tumors, kidney cancer, pituitary adenomas, and papillary thyroid cancer.

Managing Cancer Risks

PGLs and PCCs

  • Endocrinology specialists work with patients to determine appropriate risk management for hereditary endocrine tumors.
  • Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
    • Blood pressure monitoring
    • Blood work and urine analysis to monitor metanephrine levels
    • MRI or CT (whole-body and/or sectioned imaging)

Additional screenings/risk management or earlier ages of screenings/risk management may be considered based on personal risk factors and family history.

Risks to Family Members

P/LP variants in the SDHB gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a SDHB P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial SDHB P/LP variant, and both males and females can pass it on to their children.

kidney cancer scan

SDHC

Cancer Risks Associated with a Pathogenic/Likely Pathogenic Variant in SDHC

Pathogenic/likely pathogenic (P/LP) variants in the SDHC gene are currently thought to account for about10% of all hereditary neuroendocrine tumors called paragangliomas (PGLs) and pheochromocytomas (PCCs). The chance for a person with an SDHC variant to develop a PGL or PCC is estimated to be up to 25%, and there might be an increased risk for the development of other types of tumors or cancer, such as gastrointestinal stromal tumors, kidney cancer, pituitary adenomas, and papillary thyroid cancer. Given the rarity of SDHC P/LP variants, information about the true number of individuals with SDHC P/LP variants and rates of cancer is still limited.

Managing Cancer Risks

PGLs and PCCs

  • Endocrinology specialists work with patients to determine appropriate risk management for hereditary endocrine tumors.
  • Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
    • Blood pressure monitoring
    • Blood work and urine analysis to monitor metanephrine levels
    • MRI or CT (whole-body and/or sectioned imaging)

Additional screenings/risk management or earlier ages of screenings/risk management may be considered based on personal risk factors and family history.

Risks to Family Members

P/LP variants in the SDHC gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an SDHC P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial SDHC P/LP variant, and both males and females can pass it on to their children.

gastrointestinal cancer female

SDHD

Cancer Risks Associated with a Pathogenic/Likely Pathogenic Variant in SDHD

Pathogenic/likely pathogenic (P/LP) variants in the SDHD gene almost exclusively demonstrate a parent-of-origin effect, meaning that only individuals who inherit the variant from their father are at an increased risk of developing tumors. However, rare cases of tumor development have been reported in individuals who inherited the variant from their mother. The lifetime risk of developing neuroendocrine tumors called paragangliomas (PGLs) for individuals with a paternally inherited SDHD P/LP variant has been estimated to be up to 45%, though initial research identified risks up to 90%. It is estimated that up to about 50% of individuals with SDHD P/LP variants will develop a neuroendocrine tumor called a (PCC). With the variants, there might also be an increased risk for other types of tumors or cancer, such as gastrointestinal stromal tumors, kidney cancer, pituitary adenomas, and papillary thyroid cancer.

Managing Cancer Risks 

PGLs and PCCs

  • Endocrinology specialists work with patients to determine appropriate risk management for hereditary endocrine tumors.
  • Our specialists follow recommendations from the National Comprehensive Cancer Network (NCCN), including:
    • Blood pressure monitoring
    • Blood work and urine analysis to monitor metanephrine levels
    • MRI or CT (whole-body and/or sectioned imaging)

Additional screenings/risk management or earlier ages of screenings/risk management may be considered based on personal risk factors and family history.

Risks to Family Members

P/LP variants in the SDHD gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with an SDHD P/LP variant have a 1 in 2 (or 50%) chance of having the P/LP variant as well. Both males and females can inherit a familial SDHD P/LP variant, and both males and females can pass it on to their children.