2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Incidental findings in FH and SDHA genes - navigating cancer risk assessment and follow-up recommendations

Incidental findings in FH and SDHA genes - navigating cancer risk assessment and follow-up recommendations
Back to course

Pdf Summary
This analysis reviewed the phenotypes of individuals with pathogenic variants (PVs) in the FH and SDHA genes across two healthcare systems. PVs in FH are associated with FH tumor predisposition syndrome (FH-TPS) and fumarate hydratase deficiency (FHD), while PVs in SDHA are associated with hereditary paraganglioma (PGL)/pheochromocytoma (PHEO) syndrome (HPGL) and Leigh syndrome. The study identified 49 PVs (0.9%) in the FH gene and 37 PVs (0.7%) in the SDHA gene. Of the FH PV carriers, 24% had a personal history of cancer, and 16% had phenotypic cancer. Additionally, 14% had a family history of renal cancer. Notably, 37% of the PVs in FH were not previously reported in people with renal cancer or features of FH-TPS. In the SDHA gene, 53% of probands with PVs had a personal history of cancer, and 8% had a personal history of PGL/PHEO. One individual had a family history of PGL/PHEO. The c.91C>T variant was identified in 9 unrelated probands. Two carriers had PGL. The analysis concludes that the phenotype of PVs in FH and SDHA is still evolving, and there is uncertainty about the appropriateness of intensive screening for individuals without a personal or family history of related features. The reporting of phenotypic data will be crucial for clarifying tumor risks and guiding appropriate management recommendations. This research was supported by the National Cancer Institute and Intermountain Health. The significance of specific variants varied, with some associated with tumor phenotypes, some with uncertain associations, and some with no association according to Clinvar. In summary, this analysis highlights the incidental findings of PVs in the FH and SDHA genes and emphasizes the need for further research to understand the tumor risks and appropriate management strategies for individuals with these variants.

Asset Subtitle

Presenting Author - Wendy Kohlmann, MS; Co-Author - Kristen Pauley, CGC; Co-Author - Anne Naumer, MS; Co-Author - Samantha Greenberg, MS, MPH; Co-Author - Nicole Stevenson, ,; Co-Author - Kelsey Ellis, MS, LCGC; Co-Author - Aciana Franco Roberts, ,; Co-Author - Joshua Kawasaki, ,; Co-Author - Taylor Jump, BS; Co-Author - Nykole Sutherland, MS, CGC;

Meta Tag

Cancer Syndromes

Clinical History

Phenotype

Co-Author Kristen Pauley, CGC

Co-Author Anne Naumer, MS

Co-Author Samantha Greenberg, MS, MPH

Co-Author Nicole Stevenson, ,

Co-Author Kelsey Ellis, MS, LCGC

Co-Author Aciana Franco Roberts, ,

Co-Author Joshua Kawasaki, ,

Co-Author Taylor Jump, BS

Co-Author Nykole Sutherland, MS, CGC

Presenting Author Wendy Kohlmann, MS

Keywords

phenotypes

pathogenic variants

FH gene

SDHA gene

FH tumor predisposition syndrome

fumarate hydratase deficiency

hereditary paraganglioma

pheochromocytoma syndrome

tumor risks

management recommendations