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A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant

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Abstract

Pathogenic variants (PVs) in the SDHD gene increase risk for paragangliomas (PGL)/pheochromocytomas, renal cell carcinomas, and gastrointestinal stromal tumors. Penetrance in individuals with SDHD PVs varies in reported research from 40–70%, and there is limited evidence of specific genotype risks. This study aims to characterize a multi-generational family with SDHD p.Trp43* PVs and potential genotype–phenotype considerations for surveillance. Individuals with a paternally inherited SDHD p.Trp43*(c.129G > A) PV were identified. Genetic, medical and family histories were abstracted, including clinical characteristics, tumor histories, and treatment approaches. Eleven individuals with the SDHD PV in the same kindred were diagnosed with 41 SDHx-related tumors across all family members. Eight individuals developed 27 head and neck PGL of varying origins, and seven individuals developed tumors outside of the head and neck region. Many individuals had multiple tumors, and age of first tumor diagnosis ranged from age 10 to age 45 years old. Individuals with SDHD p.Trp43* variants may have higher risks for SDHx related tumors than other SDHD variants. Prioritizing identification of at-risk individuals and initiating surveillance tailored to family history is recommended given the rate of multiple tumors found in one familial branch of individuals under 18 years old. Individuals with strong family histories of PGL at young ages with this PV will benefit from tailored surveillance recommendations.

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Additional clinical data is available and limited due to patient identifiers.

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Acknowledgements

The authors express deep gratitude to all members of the patient care teams, and most importantly, to our patients and this family, without whom none of our work would be possible.

Funding

This manuscript was supported in part by grant P30 CA2014 by the National Cancer Institute, awarded to Huntsman Cancer Institute.

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Authors and Affiliations

  1. School of Medicine, University of Utah, Salt Lake City, UT, USA

    Madeline Foley

  2. Department of Endocrinology, University of Utah, Salt Lake City, UT, USA

    Anu Sharma

  3. Genetic Counseling Shared Resource, Huntsman Cancer Institute, Salt Lake City, UT, USA

    Kinley Garfield, Wendy Kohlmann & Samantha Greenberg

  4. Department of Pediatrics, University of Utah, Salt Lake City, UT, USA

    Luke Maese

  5. Division of Otolaryngology, University of Utah, Salt Lake City, UT, USA

    Luke Buchmann

  6. Huntsman Cancer Institute, Bioinformatic Analysis Shared Resource, Salt Lake City, UT, USA

    Julie Boyle

  7. Division of Oncology, University of Utah, Salt Lake City, UT, USA

    Joanne Jeter

Authors
  1. Madeline Foley
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  2. Anu Sharma
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  3. Kinley Garfield
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  4. Luke Maese
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  9. Samantha Greenberg
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by MF, SG, JB, and AS. The first draft of the manuscript was written by MF and SG and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Samantha Greenberg.

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The authors do not report any conflicts of interest.

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This manuscript is approved by the University of Utah IRB#00046740.

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Foley, M., Sharma, A., Garfield, K. et al. A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant. Familial Cancer 22, 217–224 (2023). https://doi.org/10.1007/s10689-022-00318-9

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  • DOI: https://doi.org/10.1007/s10689-022-00318-9

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