Familial paraganglioma calculating penetrance and optimal surveillance in SDHB-mutation carriers.

Eijkelenkamp, K. (Karin) (2014) Familial paraganglioma calculating penetrance and optimal surveillance in SDHB-mutation carriers. thesis, Medicine.

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Abstract

Introduction: Paragangliomas (PGLs) are rare, neuro-endocrine tumors that are hereditary in up to one third of cases. Germline mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to familial paraganglioma syndrome. Within this syndrome, head and neck paraganglioma (HNPGL), sympathetic PGL and pheochromocytoma can occur for which regular surveillance is required. It has been demonstrated that penetrance of disease in SDHB-mutation carriers is incomplete, although these studies mainly used index patients (i.e. first medically identified patient in a family) which can overestimate this proportion. Recommendations for surveillance are based on limited and probably biased evidence and there is a tendency of overscreening which has negative consequences (psychological/financial). The aim of this study was to assess the penetrance and optimal surveillance for different manifestation of SDHB-mutation carriers. Patients and methods: This retrospective study included all SDHB-mutation carriers in follow-up at the department of Endocrinology at the University Medical Center of Groningen in the period 2008 until December 2013. Penetrance was assessed for different manifestations using reverse Kaplan-Meier method. Poisson distribution model was used to calculate the hit rate and average time to detect the first and subsequent manifestation, to assess the optimal age to start surveillance and intervals. Results: Eighty-three mutation carriers were included, 33 male and 50 female. Twenty-three mutation carriers (28%) had a manifestation, of which 18 carriers were index patients. Manifestations included HNPGL (n = 15), sympathetic PGL (n = 9) and pheochromocytoma (n = 1), with an overall penetrance 35% at age 60 years. The optimal age to start surveillance for HNPGL was age 31 years, with a subsequent interval of 4 years. No optimal surveillance could be calculated due to the low number of patients with these manifestations. Conclusion: This study emphasizes the low penetrance of disease in SDHB-mutation carriers. By using a mathematical model and including unaffected carriers/familymembers, a more accurate estimation of penetrance and surveillance of these carriers is provided. The age to start screening for HNPGL could be postponed until the age of 31 years.

Item Type:	Thesis (Thesis)
Supervisor name:	Osinga, Drs. T.E. and Horst-Schrivers, Dr. A.N.A. van der and Links, Prof. dr. T.P.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:49
Last Modified:	25 Jun 2020 10:49
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1058

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