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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

A need to tailor surveillance based on family history: describing a highly penetrant familial... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Familial Cancer Springer Journals

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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Publisher
Springer Journals
Copyright
Copyright © The Author(s), under exclusive licence to Springer Nature B.V. 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
ISSN
1389-9600
eISSN
1573-7292
DOI
10.1007/s10689-022-00318-9
Publisher site
See Article on Publisher Site

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.

Journal

Familial Cancer – Springer Journals

Published: Apr 1, 2023

Keywords: SDHx; Pheochromocytoma; Tumor predisposition; Succinate dehydrogenase; Genetics; Germline mutation

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