OR35-1 Genetic Anticipation in SDHB-related pheochromocytomas and paragangliomas: Earlier onset of primary and metastatic tumors, worse prognosis and outcome in the first generation of index patients

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR35-Neoplasia of Endocrine Tissues
Bench to Bedside
Monday, June 17, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 11:15 AM
Room 122 (Moscone Center)
Tamara Prodanov*1, Victoria L Martucci1, Margarita Raygada2, Maya Beth Lodish3, Karen T Adams1, Constantine A Stratakis4, Tito Fojo5 and Karel Pacak6
1Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 2National Institutes of Health, Bethesda, MD, 3NIH, 4National Institutes of Health (NIH), Bethesda, MD, 5National Cancer Institute, National Institutes of Health, Bethesda, MD, 6NICHD/NIH, Bethesda, MD
Background: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare neoplasms of chromaffin tissue that appear in the adrenal medulla or in extra-adrenal chromaffin tissue. Approximately 1/3 of these tumors are caused by mutations in several genes (SDHA/AF2/B/C/D). Although frequently nonmetastatic and slow growing in most cases, in selected patient populations (especially those with succinate dehydrogenase subunit B (SDHB) mutations), up to 50%-90% of patients develop metastatic disease. Anticipation is a phenomenon characterized by decreasing age at onset and increasing severity of symptoms of a disease in successive generations within a pedigree.  We describe here a set of families with SDHB mutations that demonstrate a decrease in the age onset of tumors and increase in metastatic disease.

Objective/ Method: Our objective was to compare clinical characteristics and outcomes of the SDHB-related PHEOs/PGLs in the first generation with the index patients. Charts of parents and their children with SDHB mutations were carefully reviewed.

Results: A total number of 9 families with SDHB mutations were found to have PHEOs/PGLs in the first generation. In 8 out of 9 families PHEOs/PGLs were diagnosed 25-34 years earlier than in their parents, regardless of their gender. In one family the son was diagnosed 4 years later than his father, but he had metastatic disease at the time of diagnosis at age 29, unlike his father who had only recurrent disease at age 29, and is disease free at age 66. In 5 out of 9 families the first generation offspring developed metastatic disease (4 of them within one year of diagnosis), unlike their parents, who developed metastases in only 2 out of 9 families. In 1 family where both father and son developed metastatic disease, the father had metastases 4 years after diagnosis, unlike his son, who was metastatic at the time of the diagnosis.

Conclusion: The present results are suggestive of genetic anticipation in SDHB-related PHEOs/PGLs. These novel results set the basis for future studies that will explore this phenomenon in order to call for new recommendations regarding the diagnostic work-up and follow-up of children of parents presenting with SDHB-related PHEOs/PGLs.   

Nothing to Disclose: TP, VLM, MR, MBL, KTA, CAS, TF, KP

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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