Can subunit-specific phenotypes guide surveillance imaging decisions in asymptomatic SDH mutation carriers?
Nicola Tufton1,2, Anju Sahdev3, William M Drake1,2
1Department of Endocrinology, St Bartholomew's Hospital, Barts Health NHS Trust, London, UK.
Clinical Endocrinology
|October 11, 2018
Summary
Genetic screening identifies more carriers of succinate dehydrogenase (SDH) mutations. Tailored surveillance for SDH-mutated carriers, focusing on specific subunits, can improve early detection of phaeochromocytoma and paraganglioma.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Familial phaeochromocytoma and paraganglioma syndrome is linked to mutations in succinate dehydrogenase (SDH) enzyme subunits.
- Increased genetic screening identifies more asymptomatic carriers, necessitating defined surveillance strategies.
- Distinct natural histories and risks are associated with mutations in individual SDH subunits.
Purpose of the Study:
- To analyze the phenotype and malignancy risks associated with specific SDH subunit mutations.
- To determine the asymptomatic penetrance of SDH mutations.
- To propose tailored surveillance strategies for asymptomatic SDH mutation carriers.
Main Methods:
- A comprehensive PubMed search (2000-2018) identified relevant clinical cases and cohorts.
- Manual review of references in identified papers.
- Analysis of accumulated published data on SDH subunit mutations, phenotypes, malignancy risks, and asymptomatic penetrance.
Main Results:
- Asymptomatic penetrance is highest for SDHD mutations.
- Head and neck paragangliomas (PGLs) are most common with SDHD mutations; extra-adrenal abdominal PGLs with SDHB mutations.
- Malignancy risk is substantial for both PCC and abdominal PGLs in SDHB carriers (30-35%), and for HNPGLs in SDHD carriers (7.5%).
Conclusions:
- Surveillance screening for asymptomatic SDH mutation carriers can be individualized based on the specific SDH subunit affected.
- Tailored screening protocols are recommended to optimize early detection and management.
- Further research into optimal surveillance programs is warranted.
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